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IJCP Group of Publications
Volume 28, Number 3, August 2017
Dr Sanjiv Chopra Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor
Dr KK Aggarwal Padma Shri Awardee Group Editor-in-Chief Dr Veena Aggarwal Group Executive Editor
IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramachandran, Dr Samith A Shetty, Dr Vijay Viswanathan, Dr V Mohan, Dr V Seshiah, Dr Vijayakumar ENT Dr Jasveer Singh, Dr Chanchal Pal Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar, Dr Rajiv Khosla, Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff, Dr Pasricha, Dr Koushik Lahiri, Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan, Dr Vineet Suri, Dr AV Srinivasan Oncology Dr V Shanta Orthopedics Dr J Maheshwari
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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF
205 Never Ignore a Symptom, Which is Unusual, Unexplained or Occurs for the First Time in Life
KK Aggarwal
AMERICAN FAMILY PHYSICIAN
207 Acute Abdominal Pain in Children
Carin E. Reust, Amy Williams
214 Practice Guidelines 215 Photo Quiz ANESTHESIOLOGY
219 To Compare the Effect of Two Different Doses of Dexmedetomidine Added to Ropivacaine for Axillary Brachial Plexus Block
Sarla Hooda, Kirti Ksheterpal, Sudivya Sharma
CARDIOLOGY
226 Role of Flavonoids in Prevention of Coronary Heart Disease and Other Chronic Diseases
Pragati Kapoor, Pankaj Kumar
ENDOCRINOLOGY
234 Mauriac Syndrome Presenting as Primary Amenorrhea in a Case of Type 1 Diabetes Mellitus
Meet M Thacker, Pratik Vora, Mihir Thacker, Manish N Mehta
ENT
239 Hearing Levels During Various Phases of Menstrual Cycle
Jyoti Yadav
INTERNAL MEDICINE
242 Congenital Cause of Status Epilepticus in an Adult: Tuberous Sclerosis Complex
Mohamed Iliyas, Sundaramurthy
247 Anti-PL-12: Antisynthetase Syndrome
Tuhina Parveen Sarwala, Manish N Mehta, Ajay C Tanna, Jemima Bhaskar, Rajesh Sadiya
254 Ramsay Hunt Syndrome with Multidermatomal Zoster: A Case Report
Mohamed Iliyas, Viswanathan Neelakantan, Uma Devi
OBSTETRICS AND GYNECOLOGY
Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com
258 Transobturator Tape for Female Stress Incontinence: Our Experience
M Gopi Kishore, AV Sainadh
265 Evaluation of Intrauterine Lesions in Infertile Women by Transvaginal Sonography and Hysteroscopy
Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com
Princy Mittal, Khushpreet Kaur, Parneet Kaur, Arvinder Kaur, Navkiran Kaur
269 Evaluation of Patwardhan Technique in Second Stage Cesarean Section
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The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.
Rita Thakur, Ritu Sharma, Ajay Wakhloo, Dinesh Gupta
EXPERT’S VIEW
273 How to Manage Hypertension in a Patient with Acute Heart Attack?
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The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.
KK Aggarwal
MEDILAW
275 Onus to Prove Medical Negligence or Deficiency Lies on the Complainant CONFERENCE PROCEEDINGS
279 54th Annual Conference of Indian Academy of Pediatrics (PEDICON 2017) 283 7th World Congress of Diabetes (DiabetesIndia 2017) AROUND THE GLOBE
289 News and Views INSPIRATIONAL STORY
294 Story of Appreciation
Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.
LIGHTER READING
296 Lighter Side of Medicine
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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF
Dr KK Aggarwal
Padma Shri Awardee Group Editor-in-Chief
Never Ignore a Symptom, Which is Unusual, Unexplained or Occurs for the First Time in Life
I
ndigestion, persistent cough, shortness of breath, constipation, fever, headache, feeling tired all the time are some common symptoms that many of us experience, but their significance is often undermined in the rush of the day-to-day life. We often ignore symptoms or minimize their significance and delay going to the doctor. But, this is how our body tries to tell us that all is not well and it’s time to see a doctor. These symptoms are important as they may be due to a disease. At times, many of these common symptoms may signal a serious disease condition. Messages describing the ‘warning signs’ of many diseases like cancer, heart attack, stroke, etc. are often displayed in public places and even in clinics and hospitals for patients to read. Take cancer for an example. Some common warning signs of cancer have been defined:
ÂÂ
Change in bowel or bladder habits
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A sore that does not heal
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Unusual bleeding or discharge
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Thickening or lump in the breast, testicles or elsewhere
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Indigestion or difficulty swallowing
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Obvious change in the size, color, shape or thickness of a wart, mole or mouth sore
ÂÂ
Nagging cough or hoarseness
ÂÂ
Weight loss
Then there are warning signs of different types of cancer such as bowel cancer, lung cancer. Warning signs of bowel cancer may include: ÂÂ
A recent, persistent change in bowel habit
ÂÂ
A change in appearance of bowel movements
ÂÂ
Blood in the stool or rectal bleeding
ÂÂ
Feeling of incomplete evacuation
ÂÂ
Unexplained anemia
ÂÂ
Rectal/anal pain or a lump in the rectum/anus
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Abdominal pain or swelling
ÂÂ
Weight loss.
Some warning signs of lung cancer may include: ÂÂ
Persistent cough
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Change in a chronic cough
ÂÂ
Shortness of breath
ÂÂ
Pain in the chest area
ÂÂ
Wheezing
ÂÂ
Hoarseness of voice
ÂÂ
Weight loss.
And the list may go on… Often people ignore warning signals and do not address them until they fall ill, often with grave consequences. So, instead of defining warning signals for each disease condition, the Indian Medical Association (IMA) advocates universal warning signals
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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF “Never ignore a symptom which is unusual (different than usual), unexplained or occurring for the first time in life”… They may be red flags to consult a doctor as soon as possible. ÂÂ
Do not ignore first attack of acidity after the age of 40 as it may be a sign of heart attack. All wheeze is not asthma and all asthmatics do not wheeze.
ÂÂ
Do not ignore first attack of asthma after the age of 40 as it may be a sign of heart attack.
ÂÂ
You may have been getting headaches for years but if the present episode of headache is unusual, severe and unexplained, you need immediate medical attention.
ÂÂ
If you get up exhausted after hours of rest, this needs to be evaluated.
Remember the following: ÂÂ
Signals for emergent attention mean to call the doctor right away
ÂÂ
Symptoms for urgent attention mean to contact the doctor same day
ÂÂ
Symptoms for attention mean doctor to be informed in the next visit.
One should be able to differentiate emergent from urgent symptoms and signs. Emergency warrants medical attention within minutes. The window period for cardiac arrest is 10 minutes, for heart attack 3 hours, for stroke 3 hours and for stoppage of bleeding 1 hour. Stay alert to live longer and live healthy ….
■■■■
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AMERICAN FAMILY PHYSICIAN
Acute Abdominal Pain in Children CARIN E. REUST, AMY WILLIAMS
ABSTRACT Acute abdominal pain accounts for approximately 9% of childhood primary care office visits. Symptoms and signs that increase the likelihood of a surgical cause for pain include fever, bilious vomiting, bloody diarrhea, absent bowel sounds, voluntary guarding, rigidity, and rebound tenderness. The age of the child can help focus the differential diagnosis. In infants and toddlers, clinicians should consider congenital anomalies and other causes, including malrotation, hernias, Meckel diverticulum, or intussusception. In school-aged children, constipation and infectious causes of pain, such as gastroenteritis, colitis, respiratory infections, and urinary tract infections, are more common. In female adolescents, clinicians should consider pelvic inflammatory disease, pregnancy, ruptured ovarian cysts, or ovarian torsion. Initial laboratory tests include complete blood count, erythrocyte sedimentation rate or C-reactive protein, urinalysis, and a pregnancy test. Abdominal radiography can be used to diagnose constipation or obstruction. Ultrasonography is the initial choice in children for the diagnosis of cholecystitis, pancreatitis, ovarian cyst, ovarian or testicular torsion, pelvic inflammatory disease, pregnancy-related pathology, and appendicitis. Appendicitis is the most common cause of acute abdominal pain requiring surgery, with a peak incidence during adolescence. When the appendix is not clearly visible on ultrasonography, computed tomography or magnetic resonance imaging can be used to confirm the diagnosis.
Keywords: Acute abdominal pain, congenital anomalies, infectious causes, pelvic inflammatory disease, ultrasonography, computed tomography
A
cute abdominal pain accounts for approximately 9% of childhood visits to primary care.1 The initial assessment of acute abdominal pain should focus on the severity of illness and whether there is a potential surgical cause of abdominal pain. For this article, surgical cause refers to a condition that may require surgical intervention. In children presenting to the emergency department with acute abdominal pain, the incidence of appendicitis or other causes needing surgical intervention ranges from 10% to 30%2-5; however, in general, the incidence of surgical acute abdominal pain is 2%.1 HISTORY The approach to a child with acute abdominal pain should begin with an overall assessment of the child’s appearance (lethargy, eye contact, comforted by family member, interactive), food and fluid intake (decreased intake or urine output, normal intake and output), and
CARIN E. REUST, MD, MSPH, is an associate professor in clinical family and community medicine at the University of Missouri–Columbia. AMY WILLIAMS, MD, MSPH is an assistant professor in clinical family and community medicine at the University of Missouri–Columbia. Source: Adapted from Am Fam Physician. 2016;93(10):830-836.
activity level (lying still, moving about in discomfort, active). The child’s age can help in narrowing potential causes of abdominal pain (Table 16,7). History regarding abdominal pain should include associated symptoms, previous episodes of abdominal pain, and the intensity of the pain. Important associated symptoms are bilious vomiting (bowel obstruction), bloody stool (bowel ischemia), and fever. Fever at the onset of acute illness is less likely to indicate a surgical abdomen, whereas fever after the onset of vomiting or pain is consistent with developing peritonitis. Chronic, intermittent acute abdominal pain is less likely to be related to a surgical cause than a first episode of acute pain. Poorly localized pain that improves with movement is more likely visceral pain. Visceral pain receptors are located in the muscles and mucosa of hollow organs. Stretching or twisting of these receptors through obstruction or volvulus of organs causes pain. Visceral pain receptors in the stomach, lower esophagus, or duodenum cause epigastric pain; receptors in the small intestine cause periumbilical pain; and in the colon, lower abdominal pain. Pain that is sharp, localized, and worsens with movement has most likely originated from somatoparietal receptors found in the parietal peritoneum, muscle, and skin.
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AMERICAN FAMILY PHYSICIAN Table 1. Selected Differential Diagnosis of Acute Abdominal Pain in Children by Age All ages
Infants and toddlers (0 to 4 years)
School age (5 to 11 years)
Adolescents (12 to 18 years)
Appendicitis
Hirschsprung disease
Abdominal migraine
Ectopic pregnancy
Bowel obstruction
Infantile colic
Functional pain
Functional pain
Child abuse
Inguinal hernia
Henoch-SchĂśnlein purpura
Inflammatory bowel disease
Constipation
Intussusception
Intussusception
Irritable bowel syndrome
Dietary indiscretions
Lactose intolerance
Lead poisoning
Menstrual-related condition
Gallbladder disease
Lead poisoning
Mononucleosis
Mononucleosis
Gastroenteritis
Malrotation of the midgut
Volvulus
Omental infarction
Hemolytic uremic syndrome
Meckel diverticulum
Other pregnancy issues
Mesenteric adenitis
Volvulus
Ovarian or testicular torsion
Pancreatitis
Pelvic inflammatory disease
Sickle cell crisis
Sexually transmitted infection
Trauma Upper respiratory infection Urinary tract infection Information from references 6 and 7.
It is important to ask about other associated symptoms because a variety of etiologies cause abdominal pain in children (Table 21,8-14). Abdominal pain with cough, shortness of breath, or sore throat can be due to respiratory infection. Urinary symptoms can indicate a urinary tract infection or pyelonephritis. In pubertal girls, it is important to ask about menstrual history and sexual activity. Vaginal discharge, with or without fever, irregular spotting, or abnormal menstrual bleeding with pain can indicate pelvic inflammatory disease.
mass. Gentle palpation can elicit guarding, and percussion without deep palpation can elicit rebound pain. Guarding and rebound pain can be consistent with peritonitis. Signs suggestive of the possible need for surgery for acute abdominal pain are listed in Table 3. Rectal examination may be necessary to identify a pelvic abscess or occult blood in the stool. Pelvic examination is required in pubertal girls to evaluate for pregnancy complications and sexually transmitted infections; scrotal examination is indicated in boys.
PHYSICAL EXAMINATION
DIAGNOSTIC EVALUATION
A complete examination with attention to pharyngeal erythema or exudate and focal consolidation in the lungs should be performed in children with acute abdominal pain. An abdominal examination in a sick, crying child can be difficult to perform. A family member can assist by placing his or her hands on the abdomen with the examiner’s hands on top of them until the child allows the examination. Asking the child to point to the part of the abdomen that hurts the most, and then initially avoiding that area, can also facilitate the examination. Auscultation of bowel sounds can help a clinician understand where the abdomen is painful because the child may try to block the stethoscope from that area. Absent bowel sounds can indicate ileus or peritonitis, whereas hyperactive bowel sounds may indicate obstruction. Beginning palpation just above the iliac crest in the lower quadrants of the abdomen will help identify an enlarged liver, spleen, or other abdominal
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Laboratory Initial laboratory tests should include a complete blood count, erythrocyte sedimentation rate or C-reactive protein, a pregnancy test, if indicated, and urinalysis.15-18 A clean void urinalysis is as accurate as a suprapubic aspiration15; the accuracy of a bag, diaper, or pad specimen is inconsistent.19,20 A urine dipstick positive for leukocytes, esterase, and nitrite is concerning for a urinary tract infection (pooled positive likelihood ratio of 28.2 in children younger than five years [95% confidence interval, 17.3 to 46.0]).15,21 Other tests may include liver function tests; amylase, lipase, or both for pancreatitis; sexually transmitted infection testing (Chlamydia trachomatis, Neisseria gonorrhoeae); and stool studies (Escherichia coli and Campylobacter, Cryptosporidium, Salmonella, and Shigella species), including evaluation for occult blood.
AMERICAN FAMILY PHYSICIAN Table 2. Clinical Features of Selected Causes of Acute Abdominal Pain in Children Condition
Clinical findings
Age
Comments
Abdominal migraine
Anorexia, nausea, vomiting, headache, photophobia
3 to 10 years
Boys and girls equally affected8
Colic
Persistent crying without apparent cause
Younger than 3 months Nonacute abdominal examination
Constipation
Hard, infrequent stooling
All age groups
May be most common cause of abdominal pain1
Gastroenteritis or colitis
Diarrhea, with vomiting or fever
All age groups
Campylobacter, Cryptosporidium, Escherichia coli, Salmonella, Shigella, rotavirus
Hirschsprung disease
Constipation, severe diarrhea, bowel obstruction, perforation, sepsis
Infant
Delayed passage of meconium (more than 24 hours) in about 57% of cases9
Inflammatory bowel disease
Bloody diarrhea
Primarily adolescents
Childhood prevalence of Crohn disease is 43 per 100,000; of ulcerative colitis, 28 per 100,00010
Omental infarction
Lower abdominal pain, vomiting, diarrhea
School-aged, overweight males11
Self-limiting, diagnosed on computed tomography12
Ovarian cyst
Lower abdominal pain
Adolescent females
Types include hemorrhagic, ruptured, and ovulatory, and torsion of a cyst
Pneumonia
Cough, shortness of breath, fever, tachypnea
All age groups
Lower lobe pneumonia
Pyelonephritis
Flank tenderness, fever, nausea and vomiting
All age groups
Oral antibiotics for 10 to 14 days as effective as intravenous antibiotics13
Sexually transmitted infection
Vaginal or penile discharge, fever
Adolescent
Chlamydia trachomatis, Neisseria gonorrhoeae
Streptococcal pharyngitis
Sore throat, fever
Older than 3 years
Rapid strep test or culture
Urinary tract infection
Dysuria, urinary frequency, urinary urgency, hematuria
All age groups, primarily females and uncircumcised infants
Point prevalence in children older than one year is 7.8%14
Information from references 1, and 8 through 14.
Table 3. Signs Indicating the Possible Need for Surgery in Patients with Acute Abdominal Pain Absent bowel sounds Bilious vomiting Bloody diarrhea or occult blood in stool Elevated temperature (≥ 100.4°F [38.0°C]) Rebound tenderness Rigidity (involuntary guarding) Voluntary guarding
Imaging Radiation exposure is an important consideration before imaging in children. Radiation dose is dependent on the child’s size. The cumulative effect of exposure over a lifetime of imaging needs to be assessed. Computed tomography (CT) of the abdomen and pelvis exposes
a child to the equivalent of more than 100 chest radiographs. The risk of a radiation-induced solid cancer is estimated to be one per 300 to 390 CT scans of the abdomen and pelvis for girls, and one per 670 to 760 scans for boys.22 The American College of Radiology Appropriateness Criteria offer recommendations for imaging children with abdominal pain (http://www.acr. org/Quality-Safety/Appropriateness-Criteria). Ultrasonography is relatively inexpensive and does not expose the patient to radiation. It is the first-line imaging choice for undifferentiated acute abdominal pain, unless history or physical examination identifies a specific diagnosis.23-28 Ultrasonography can be used to evaluate for bowel thickening in inflammatory bowel disease, focal intramural bowel hematomas in HenochSchönlein purpura, and bowel “target” or “donut” sign in intussusception.27,29 It is also the primary imaging
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AMERICAN FAMILY PHYSICIAN choice for pyloric stenosis, cholecystitis, pancreatitis, renal calculi, ovarian cysts, ovarian torsion, and pregnancy complications.27,28
the child’s body habitus.30,31 Ultrafast 3T magnetic resonance imaging requires only six minutes, does not require sedation, and has no radiation exposure.32
Ultrasonography is the imaging tool of choice for evaluation of appendicitis, followed by CT or magnetic resonance imaging (MRI) for equivocal findings.30,31 The sensitivity of ultrasonography is decreased in centers where it is used less often, when the appendix is not clearly visualized, and when there is shorter duration of pain; sensitivity is also dependent on
Abdominal radiography is more likely to be diagnostic in patients with previous abdominal surgery, abnormal bowel sounds, abdominal distension, or peritoneal signs. Radiography may identify a renal or ureteric calculus, abdominal mass, ingested foreign body (including bezoars), bowel perforation with free air, and constipation.12,27,33 CT of the abdomen may be required
Evaluation and Diagnosis of Acute Abdominal Pain in Children Bilious vomiting, bloody diarrhea, or fever, with rebound tenderness, rigidity, or voluntary guarding? Yes
No
Consider surgical consultation
Bloody diarrhea?
Diarrhea No
Obtain laboratory results (CBC, ESR or CRP, urinalysis, β-hCG), and perform imaging as indicated by clinical presentation Consider appendicitis, bowel obstruction, bowel perforation, incarcerated hernia, intussusception, malrotation of the midgut, ovarian torsion, testicular torsion, volvulus
Yes
If mild to moderate presentation, most likely viral gastroenteritis including rotavirus
Constipation
Consider dysentery, infectious enteritis or colitis, inflammatory bowel disease
Abdominal radiography Consider constipation, bowel obstruction
Risk factors for pregnancy or STI
β-hCG measurement, gonorrhea and chlamydia testing, pelvic or transvaginal ultrasonography Consider pregnancyor STI-related disease or complication
Urinary symptoms
Urinalysis Consider urinary tract infection
Respiratory symptoms
Chest radiography Rapid strep test
If the diagnosis is undetermined and not acute, consider observation, with monitoring instructions for parents, and repeating the examination in 24 to 48 hours
Consider pneumonia, streptococcal pharyngitis, other upper respiratory infection
Figure 1. Algorithm for the evaluation and diagnosis of acute abdominal pain in children. β-hCG = Beta human chorionic gonadotropin; CBC = Complete blood count; CRP = C-reactive protein; ESR = Erythrocyte sedimentation rate; STI = Sexually transmitted infection.
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AMERICAN FAMILY PHYSICIAN to diagnose complications such as necrosis from pancreatitis or abscess formation in appendicitis27,33 and may be used for the diagnosis of omental torsion or mesenteric lymphadenitis.33 MANAGEMENT OF ACUTE ABDOMINAL PAIN A quick workup is needed for a sick-appearing child, with attention to hydration status and pain control. For severe pain, opiates should be used and will not delay or affect the accuracy of diagnosis.34-36 Urgent surgical consultation should not be delayed while awaiting diagnostic workup. If a child does not have an acute surgical abdomen and the diagnosis is undetermined, the examination should be repeated in 24 to 48 hours. Up to 30% of children will have a change in their diagnosis.37 Figure 1 outlines the approach to the evaluation and diagnosis of acute abdominal pain.
Surgical Causes of Acute Abdominal Pain Appendicitis can occur at any age but has a peak incidence during adolescence because of lymphoid follicular hyperplasia.16 Clinical examination does not distinguish appendicitis from mesenteric lymphadenitis.38 There are a variety of clinical prediction rules for appendicitis. The best validated
systems are the Pediatric Appendicitis Score and the Alvarado score, which uses the mnemonic MANTRELS for the characteristics it evaluates (Table 4).39 In general, prediction rules overestimate appendicitis by 30% and miss 3% to 5% of cases. A child with fever, rebound tenderness, a history of mid-abdominal pain migrating to the right lower quadrant, and an elevated white blood cell count, erythrocyte sedimentation rate, or C-reactive protein level should be evaluated for appendicitis16,40 (eTable A).
Infants and Toddlers In infants and toddlers, acute abdominal pain may be caused by intussusception and congenital anomalies, including Meckel diverticulum, malrotation of the midgut, and inguinal hernias. Intussusception usually occurs before two years of age.41 Infants and toddlers may present with right lower quadrant tenderness, a sausage-shaped mass in the abdomen, and red currant jelly stool caused by venous congestion of intussuscepted bowel.41 However, the classic triad of colicky abdominal pain, vomiting, and bloody stool is found in less than 50% of cases.29,41 In children, 90% of cases of intussusception are idiopathic, with 10% of cases resulting from a lead point or sticky spot in the
eTable A. Likelihood Ratios Related to Appendicitis LR+ (95% CI)
LR– (95% CI)
3.4 (2.4 to 4.8)
0.32 (0.16 to 0.64)
3.0 (2.3 to 3.9)
0.28 (0.14 to 0.55)
1.9 (1.4 to 2.5)
0.72 (0.62 to 0.85)
Erythrocyte sedimentation rate > 20 mm per hourA4
3.8 (1.8 to 8.1)
0.68 (0.56 to 0.81)
C-reactive protein > 10 mg per L (95.24 nmol per L)A4
3.6 (2.1 to 6.2)
0.44 (0.33 to 0.59)
2.0 (1.3 to 2.9)
0.22 (0.17 to 0.30)
4.0 (3.2 to 4.9)
0.20 (0.09 to 0.41)
2.4 (2.0 to 2.8)
0.27 (0.20 to 0.37)
Signs and symptoms FeverA1 Rebound
tendernessA2
Mid-abdominal pain migrating to right lower quadrantA3 Laboratory tests
White blood cell count > 10,000 per
mm3
(10.00 ×
109
per
L)A2
Prediction scores Alvarado (MANTRELS) ≥ 7A2 Pediatric Appendicitis Score ≥
6A5
CI = Confidence interval; LR+ = Positive likelihood ratio; LR– = Negative likelihood ratio. Information from: A1. O’Shea JS, Bishop ME, Alario AJ, Cooper JM. Diagnosing appendicitis in children with acute abdominal pain. Pediatr Emerg Care. 1988;4(3):172-176. A2. Bundy DG, Byerley JS, Liles EA, Perrin EM, Katznelson J, Rice HE. Does this child have appendicitis? JAMA. 2007;298(4):438-451. A3. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RG. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics. 2005;116(3):709-716. A4. Pelota H, Ahlqvist J, Rapola J, et al. C-reactive protein compared with white blood cell count and erythrocyte sedimentation rate in the diagnosis of acute appendicitis in children. Acta Chir Scand. 1986;152:55-58. A5. Schneider C, Kharbanda A, Bachur R. Evaluating appendicitis scoring systems using a prospective pediatric cohort. Ann Emerg Med. 2007;49(6):778-784.e.1.
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AMERICAN FAMILY PHYSICIAN colon.41 Air or contrast enema can be diagnostic and therapeutic for intussusception. Symptomatic Meckel diverticulum can present with gastrointestinal bleeding, diverticulitis, bowel obstruction, peritonitis, intussusception, or volvulus. One-half of such cases occur in children younger than four years.12,41 Malrotation of the midgut leading to volvulus causes bilious vomiting, pain, diarrhea, and bloody stools in more advanced cases. Incarcerated inguinal hernias present with a tender groin mass.
Adolescents In adolescents, acute abdominal pain may result from a gonad- or pregnancy-related pathology. Ovarian torsion presents with intermittent, nonradiating unilateral lower abdominal pain with an enlarged adnexa on ultrasonography or CT.42 Testicular torsion commonly presents with a tender scrotum and enlarged testis in adolescents, but boys may present with a complaint of hip or abdominal pain with nausea or vomiting. Ectopic pregnancy and early pregnancy loss must be considered in adolescent girls. Both conditions may present with vaginal bleeding, cramping pain, and abdominal tenderness. An intrauterine pregnancy should be visualized with transvaginal ultrasonography when the beta human chorionic gonadotropin level is 1,500 to 2,000 mIU per mL (1,500 to 2,000 IU per L).43 Early pregnancy loss may be seen as an empty gestational sac or gestational sac without fetal heart activity on transvaginal ultrasonography.44 Repeat ultrasonography and serial beta human chorionic gonadotropin testing may be required to confirm pregnancy loss.
5. Tsalkidis A, Gardikis S, Cassimos D, et al. Acute abdomen in children due to extra-abdominal causes. Pediatr Int. 2008;50(3):315-318. 6. Leung AK, Sigalet DL. Acute abdominal pain in children. Am Fam Physician. 2003;67(11):2321-2326. 7. Montgomery DF, Hormann MD. Acute abdominal pain: a challenge for the practitioner. J Pediatr Health Care. 1998;12(3):157-159. 8. Carson L, Lewis D, Tsou M, et al. Abdominal migraine: an under-diagnosed cause of recurrent abdominal pain in children. Headache. 2011;51(5):707-712. 9. Singh SJ, Croaker GD, Manglick P, et al. Hirschsprung’s disease: the Australian Paediatric Surveillance Unit’s experience. Pediatr Surg Int. 2003;19(4):247-250. 10. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5(12):1424-1429. 11. Gosain A, Blakely M, Boulden T, et al. Omental infarction: preoperative diagnosis and laparoscopic management in children. J Laparoendosc Adv Surg Tech A. 2010; 20(9):777-780. 12. Saito JM. Beyond appendicitis: evaluation and surgical treatment of pediatric acute abdominal pain. Curr Opin Pediatr. 2012;24(3):357-364. 13. Strohmeier Y, Hodson EM, Willis NS, Webster AC, Craig JC. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2014;(7):CD003772. 14. Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J. 2008;27(4):302-308. 15. Whiting P, Westwood M, Watt I, Cooper J, Kleijnen J. Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review. BMC Pediatr. 2005;5(1):4.
Note: For complete article visit: www.aafp.org/afp.
16. Bundy DG, Byerley JS, Liles EA, Perrin EM, Katznelson J, Rice HE. Does this child have appendicitis? JAMA. 2007;298(4):438-451.
REFERENCES
17. Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA. 2007;298(24):2895-2904.
1. Loening-Baucke V, Swidsinski A. Constipation as cause of acute abdominal pain in children. J Pediatr. 2007;151(6):666-669.
18. Kwan KY, Nager AL. Diagnosing pediatric appendicitis: usefulness of laboratory markers. Am J Emerg Med. 2010;28(9):1009-1015.
2. Farion KJ, Michalowski W, Rubin S, Wilk S, Correll R, Gaboury I. Prospective evaluation of the MET-AP system
providing triage plans for acute pediatric abdominal pain. Int J Med Inform. 2008;77(3):208-218.
3. O’Shea JS, Bishop ME, Alario AJ, Cooper JM. Diagnosing
appendicitis in children with acute abdominal pain. Pediatr Emerg Care. 1988;4(3):172-176.
4. Reynolds SL, Jaffe DM. Diagnosing abdominal pain in a pediatric emergency department. Pediatr Emerg Care. 1992;8(3):126-128.
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19. Etoubleau C, Reveret M, Brouet D, et al. Moving from bag to catheter for urine collection in non-toilet-trained children suspected of having urinary tract infection: a paired comparison of urine cultures. J Pediatr. 2009;154(6):803-806. 20. McGillivray D, Mok E, Mulrooney E, Kramer MS. A headto-head comparison: “clean-void” bag versus catheter urinalysis in the diagnosis of urinary tract infection in young children. J Pediatr. 2005;147(4):451-456. 21. White B. Diagnosis and treatment of urinary tract infections in children. Am Fam Physician. 2011;83(4):409-415.
AMERICAN FAMILY PHYSICIAN 22. Miglioretti DL, Johnson E, Williams A, et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr. 2013;167(8):700-707. 23. Yarmish GM, Smith MP, Rosen MP, et al. American College of Radiology. ACR appropriateness criteria. Right upper quadrant pain. http://www.acr.org/~/media/ ACR/Documents/AppCriteria/Diagnostic/RightUpper Quadrant Pain.pdf. Accessed January 23, 2016. 24. Bhosale PR, Javitt MC, Atri M, et al. ACR appropriateness criteria. Acute pelvic pain in the reproductive age group. [Published ahead of print November 19, 2015]. Ultrasound Q. http://journals.lww.com/ultrasoundquarterly/Abstract/ publishahead/ACR_Appropriateness_Criteria_R__ Acute_Pelvic_Pain.99880.aspx. Accessed January 23, 2016. 25. Karmazyn B, Coley BD, Binkovitz LA, et al. American College of Radiology. ACR appropriateness criteria. Urinary tract infection—child. http://www.acr.org/~/ media/ACR/Documents/AppCriteria/Diagnostic /Urinary Tract Infection Child.pdf. Accessed January 23, 2016. 26. Smith MP, Katz DS, Rosen MP, et al. American College of Radiology. ACR appropriateness criteria. Right lower quadrant pain—suspected appendicitis. http://www.acr. org/~/media/7425a3e08975451eab571a316db4ca1b.pdf. Accessed January 23, 2016. 27. Hayes R. Abdominal pain: general imaging strategies. Eur Radiol. 2004;14(suppl 4):L123-L137. 28. Shah S. An update on common gastrointestinal emergencies. Emerg Med Clin North Am. 2013;31(3): 775-793. 29. Mendez D, Caviness AC, Ma L, Macias CC. The diagnostic accuracy of an abdominal radiograph with signs and symptoms of intussusception. Am J Emerg Med. 2012; 30(3):426-431. 30. Mittal MK, Dayan PS, Macias CG, et al.; Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Performance of ultrasound in the diagnosis of appendicitis in children in a multicenter cohort. Acad Emerg Med. 2013;20(7): 697-702. 31. Bachur RG, Dayan PS, Bajaj L, et al.; Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. The effect of abdominal pain duration on the accuracy of diagnostic imaging for pediatric appendicitis. Ann Emerg Med. 2012;60(5): 582-590.e3.
abdominal pain for the detection of appendicitis. AJR Am J Roentgenol. 2012;198(6):1424-1430. 33. Carty HM. Paediatric emergencies: non-traumatic abdominal emergencies. Eur Radiol. 2002;12(12): 2835-2848. 34. Green R, Bulloch B, Kabani A, Hancock BJ, Tenenbein M. Early analgesia for children with acute abdominal pain. Pediatrics. 2005;116(4):978-983. 35. Ranji SR, Goldman LE, Simel DL, Shojania KG. Do opiates affect the clinical evaluation of patients with acute abdominal pain? JAMA. 2006;296(14):1764-1774. 36. Sharwood LN, Babl FE. The efficacy and effect of opioid analgesia in undifferentiated abdominal pain in children: a review of four studies. Paediatr Anaesth. 2009;19(5): 445-451. 37. Toorenvliet BR, Bakker RF, Flu HC, Merkus JW, Hamming JF, Breslau PJ. Standard outpatient re-evaluation for patients not admitted to the hospital after emergency department evaluation for acute abdominal pain. World J Surg. 2010;34(3):480-486. 38. Toorenvliet B, Vellekoop A, Bakker R, et al. Clinical differentiation between acute appendicitis and acute mesenteric lymphadenitis in children. Eur J Pediatr Surg. 2011;21(2):120-123. 39. Ebell MH, Shinholser J. What are the most clinically useful cutoffs for the Alvarado and Pediatric Appendicitis Scores? A systematic review. Ann Emerg Med. 2014;64(4): 365-372.e2. 40. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RG. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics. 2005;116(3):709-716. 41. Pepper VK, Stanfill AB, Pearl RH. Diagnosis and management of pediatric appendicitis, intussusception, and Meckel diverticulum. Surg Clin North Am. 2012; 92(3):505-526, vii. 42. Appelbaum H, Abraham C, Choi-Rosen J, Ackerman M. Key clinical predictors in the early diagnosis of adnexal torsion in children. J Pediatr Adolesc Gynecol. 2013; 26(3):167-170. 43. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin no. 94. Medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479-1485.
44. Committee on Practice Bulletins—Gynecology. American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 32. Johnson AK, Filippi CG, Andrews T, et al. Ultrafast 3-T MRI in the evaluation of children with acute lower 2015;125(5):1258-1267. ■■■■
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Practice Guidelines ACIP RELEASES 2017 CHILDHOOD IMMUNIZATION RECOMMENDATIONS The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention reviews and updates the childhood immunization schedule annually to reflect recently published updates or corrections from the previous year. The 2017 childhood immunization schedule is available at http:// www.aafp.org/patient-care/immunizations/schedules. html. This year’s schedule features a new table and several key recommendation changes.
General Recommendations The ACIP continues to recommend that any dose not given at the recommended age be given at the next possible opportunity. In general, using combination vaccines is preferred over separate injections of equivalent component vaccines. Clinically significant adverse events that follow vaccination should be reported to the Vaccine Adverse Event Reporting System online (https://vaers.hhs.gov/index) or via telephone (800-822-7967).
Human Papillomavirus Vaccine A two-dose human papillomavirus vaccine series (zero, six to 12 months) is recommended for adolescents who begin the series before 15 years of age. Routine vaccination at 11 to 12 years of age is recommended. To be considered immunized, five or more months must have passed between the first and second doses of vaccine, otherwise a third dose should be given at six months. For adolescents who receive the first dose before 15 years of age but will receive the second dose after age 15, two doses are sufficient if provided at least five months apart. Immunocompromised persons (regardless of age) and anyone starting the series after 15 years of age, should continue to receive the threedose (zero, one to two, six months) schedule.1
Influenza Vaccine Noting the recent lack of effectiveness with the use of live attenuated influenza vaccine, it should not be used during the 2016-2017 influenza season.2
Source: Adapted from Am Fam Physician. 2017;95(4):260-261.
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Hepatitis B Vaccine Emphasizing the importance of delivering the first dose of vaccine early and without regard to the birthing location, ACIP changed the recommendation from “at hospital discharge” to “within 24 hours of birth.”
Tdap Vaccine Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine continues to be recommended routinely at 11 to 12 years of age. A new preferential recommendation for Tdap administration during pregnancy (specifically at 27 to 36 weeks’ gestation) impacts pregnant adolescents and young women.
Meningococcal Vaccines Young adults 16 through 23 years of age (preferred 16 to 18 years of age) who are not at increased risk of meningococcal disease may be vaccinated with a two-dose series of either serogroup B meningococcal vaccine product. The products are not interchangeable. During an outbreak, the recommendation is to use the two-dose (MenB-4C), or three-dose (MenBFHbp) series. ACIP clarified that the recommended use of serogroup A, C, W, and Y (MenACWY) and serogroup B vaccines is the same regardless of human immunodeficiency virus status or CD4 count in children and adolescents.3
Vaccines for Specific Medical Conditions A new chart is provided to give clearer guidance on which high-risk conditions may require an altered vaccine administration schedule. Arranged by condition, the chart shows which vaccines are contraindicated or require special administration instructions. REFERENCES 1. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination— updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408. 2. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines. MMWR Recomm Rep. 2016;65(5):1-54. 3. MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW. Recommendations for use of meningococcal conjugate vaccines in HIV-infected persons—Advisory Committee on Immunization Practices, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(43):1189-1194.
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Photo Quiz PRURITIC RASH IN PREGNANCY A 29-year-old woman (gravida 4, para 2) presented at 29 weeks’ gestation with the sudden appearance of scattered periumbilical and lower extremity pruritic papules. Despite treatment with topical hydrocortisone valerate and oral diphenhydramine, the rash spread to her entire abdomen and all four extremities. Physical examination revealed ovoid plaques with targetoid features and erythematous nodules (Figures 1 and 2). Her face and mucous membranes were not affected. The pruritus intensified, and her symptoms did not respond to an increased dose of topical or oral corticosteroids. Her medical and obstetric histories were unremarkable, including no history of similar rashes. She had no new exposures. A skin biopsy revealed prominent linear staining of the epidermal basement membrane for C3 and lesser staining for immunoglobulin G (IgG).
Figure 1.
Question Based on the patient’s history, physical examination, and histologic findings, which one of the following is the most likely diagnosis? A. Intrahepatic cholestasis of pregnancy. B. Pemphigoid gestationis. C. Prurigo gestationis. D. Pruritic urticarial papules and plaques of pregnancy (PUPPP). Figure 2.
SEE THE FOLLOWING PAGE FOR DISCUSSION.
Source: Adapted from Am Fam Physician. 2017;95(7):453-454.
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AMERICAN FAMILY PHYSICIAN Summary Table Condition
Location
Characteristics
Intrahepatic cholestasis of Pruritus usually begins on the palms and soles, Not a primary dermatologic condition; lesions may pregnancy and then becomes more widespread develop from intense pruritus and subsequent scratching; may cause linear excoriations and papules Pemphigoid gestationis
Begins in the periumbilical region with Lesions vary in appearance, including erythematous subsequent spread to the remainder of the papules, urticarial plaques, targetoid lesions, and bullae; abdomen and extremities may be associated with preterm delivery; biopsy required for diagnosis
Prurigo gestationis
May have typical atopic distribution (face, neck, Eczematous lesions; patients may have a history of atopic and flexural regions of extremities) or it may dermatitis; thought to be a flare-up of underlying atopic be more widespread dermatitis
Pruritic urticarial papules Typically begins on the abdomen within striae, Pruritic papules that coalesce into urticarial plaques and plaques of pregnancy and then spreads to the chest, legs, and arms; the periumbilical region is usually spared
Discussion The answer is B: pemphigoid gestationis, an uncommon skin disorder that occurs in one out of 50,000 pregnancies.1 The condition initially presents as intense periumbilical pruritus, usually in the second or third trimester. Skin lesions develop after the onset of pruritus and may include erythematous papules, urticarial plaques, and targetoid lesions. Over the course of several weeks, the rash spreads to the remainder of the abdomen and extremities, and subepidermal bullae may form. The pathogenesis of pemphigoid gestationis is not well understood, but it is thought to be autoimmune and involve circulating IgG targeted at the epithelial basement membrane.1,2 A definitive diagnosis of pemphigoid gestationis requires a biopsy demonstrating linear staining of the basement membrane for C3 deposition.3 Pemphigoid gestationis can affect the health outcome of the fetus, unlike PUPPP and prurigo gestationis. There may be an increased risk of spontaneous miscarriage and fetal demise, but the data are conflicting. One study of 87 pregnancies complicated by pemphigoid gestationis found no increased risk of miscarriage,2 whereas a small study found that although the overall miscarriage rate was not increased, the rate of late miscarriages and fetal demise was increased.4 Between 16% and 34% of patients with pemphigoid gestationis give birth prematurely5; the risk is higher when it presents in the first or second trimester or if blisters develop.4 Pemphigoid gestationis spontaneously regresses within six months of delivery; however, there is a risk of recurrence in subsequent pregnancies, with oral contraceptive use, and during menses.2 Pemphigoid gestationis has been associated with autoimmune disease, particularly autoimmune thyroid diseases
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such as Graves disease and Hashimoto disease.2,3 Intrahepatic cholestasis of pregnancy is not a primary skin disorder, but skin lesions may appear secondary to the intense pruritus and subsequent scratching induced by cholestasis.3 Pruritus usually begins on the palms and soles, and then becomes more widespread. Scratching may cause linear excoriations and papules. Prurigo gestationis is the most common dermatosis of pregnancy and is thought to represent a flare-up of underlying atopic dermatitis. It presents as benign eczematous lesions. The lesions may be limited to the typical atopic distribution (face, neck, and flexural regions of extremities) or more widespread. PUPPP may be distinguished from pemphigoid gestationis by the sparing of the periumbilical region. The benign, self-limited rash typically begins on the abdomen within striae and then spreads to the chest, legs, and arms. It appears as pruritic papules that coalesce into urticarial plaques. REFERENCES 1. Bedocs PM, Kumar V, Mahon MJ. Pemphigoid gestationis: a rare case and review. Arch Gynecol Obstet. 2009;279(2):235-238. 2. Jenkins RE, Hern S, Black MM. Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp Dermatol. 1999;24(4):255-259. 3. Bergman H, Melamed N, Koren G. Pruritus in pregnancy: treatment of dermatoses unique to pregnancy. Can Fam Physician. 2013;59(12):1290-1294. 4. Chi CC, Wang SH, Charles-Holmes R, et al. Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes. Br J Dermatol. 2009; 160(6):1222-1228. 5. Huilaja L, Mäkikallio K, Tasanen K. Gestational pemphigoid. Orphanet J Rare Dis. 2014;9:136.
ANESTHESIOLOGY
To Compare the Effect of Two Different Doses of Dexmedetomidine Added to Ropivacaine for Axillary Brachial Plexus Block SARLA HOODA*, KIRTI KSHETERPAL†, SUDIVYA SHARMA‡
ABSTRACT Background: The present prospective, randomized, double-blinded study compared the effect of two different doses of dexmedetomidine added to ropivacaine for axillary brachial plexus block. Material and methods: Seventy-five American Society of Anesthesiologists physical status I-II patients receiving axillary brachial plexus block for upper limb surgery using a multiple injection technique through peripheral nerve stimulator, were randomly allocated to three groups depending upon the use and the dose of dexmedetomidine used with ropivacaine. Group R (n = 25) received 34 mL of 0.5% ropivacaine plus 1 mL of normal saline, Group RD75 (n = 25) received 34 mL of 0.5% ropivacaine plus 0.75 mL (75 µg) dexmedetomidine plus 0.25 mL of normal saline. Group RD100 (n = 25) received 34 mL of 0.5% ropivacaine plus 1 mL (100 µg) dexmedetomidine. Time taken to administer the block; onset of sensory and motor block; duration of sensory and motor block, duration of analgesia; sedation scores; hemodynamic parameters; complications and patient satisfaction were studied. Results: Mean onset time of sensory and motor block was comparable in three groups. Duration of sensory and motor block was longer in groups RD75 and RD100 than Group R. Groups RD75 and RD100 patients experienced lower blood pressures, but incidence of bradycardia and hypotension was insignificant. Conclusion: Addition of dexmedetomidine as an adjuvant to ropivacaine in axillary brachial plexus block extends the duration of sensory and motor block, and also prolongs the analgesia period. The two dosages of dexmedetomidine being comparable, we recommend the use of lower dose.
Keywords: Dexmedetomidine, ropivacaine, axillary brachial plexus block, normal saline, sensory and motor block,
analgesia
B
rachial plexus block provides ideal operating conditions for upper limb surgery. It produces prolonged analgesia and complete relaxation of the muscles, thus simplifying reduction of fractures, dislocations or approximation of severed tendons. It blocks the sympathetic supply to the blood vessels, which reduces postoperative vasospasm, pain and edema. It also renders postoperative period free from nausea, vomiting, cerebral depression and pain, commonly associated with general anesthesia. Depending upon different anatomical levels, brachial
*Senior Professor and HOD (Registrar, University of Health Sciences) †Associate Professor ‡Junior Resident Dept. of Anesthesiology and Critical Care Pt BD Sharma, PGIMS, Rohtak, Haryana Address for correspondence Dr Sudivya Sharma Flat No. 16, Shubham Building, Mumbai - 400 088, Maharashtra E-mail: drsudivyasharma@gmail.com
plexus can be blocked by interscalene, supraclavicular, infraclavicular and axillary route. The interscalene block is performed at the trunk level of brachial plexus, supraclavicular block at the transition between divisions and cords, infraclavicular at the level of cords and axillary block at the terminal nerve level. Axillary approach to brachial plexus blockade has the advantage of being performed at the level away from the pleura and neuraxial structures, so it is ideal for obtaining complete block of upper extremity with a minimum of discomfort and complications. Thus, the ease of performance and safety has made anesthesiologists more proficient with axillary approach of brachial plexus blockade for surgical procedures performed on distal humerus, elbow and proximal forearm. Lignocaine, bupivacaine and levobupivacaine are local anesthetics that have been in use for long. Recently ropivacaine has gained popularity for brachial plexus block. Ropivacaine is an aminoamide, a monohydrate of
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ANESTHESIOLOGY the hydrochloride salt of 1-propyl-2´,6´-pipecoloxylidide and is prepared as pure S-enantiomer. Its single enantiomer composition and lower lipid solubility results in its being less cardiotoxic than bupivacaine. It is prepared as a plain solution without epinephrine due to its unique intrinsic vasoconstrictor activity. Additives have been added to local anesthetics to improve their quality and duration of block. The commonly used adjuvants are epinephrine, clonidine, fentanyl, sufentanil, morphine and recently dexmedetomidine. The aims of co-administration are to accelerate the onset time, reduce the systemic absorption of local anesthetic to avoid systemic toxicity and to prolong the duration of nerve block. Alpha (α) 2-adrenergic receptor (AR) agonists are known for their sedative, analgesic, perioperative sympatholytic, anesthetic-sparing and hemodynamic-stabilizing properties. Dexmedetomidine, a highly selective α2AR agonist with a relatively high ratio of α2/α1activity (1620:1 as compared to 220:1 for clonidine), possesses all these properties but lacks respiratory depression, making it a useful and safe adjunct in diverse clinical applications. The hypnotic and supraspinal analgesic effects of dexmedetomidine are mediated by the hyperpolarization of noradrenergic neurons, which suppresses neuronal firing in the locus ceruleus along with inhibition of norepinephrine release and activity in the descending medullospinal noradrenergic pathway, secondary to activation of central α2-ARs. Suppression of activity in the descending noradrenergic pathway, which modulates nociceptive neurotransmission, terminates propagation of pain signals leading to analgesia. To the best of our knowledge, no study so far, has been reported in literature where dexmedetomidine was added to ropivacaine for axillary brachial plexus block. Hence, this study was conducted to evaluate the effect of addition of two different doses of dexmedetomidine i.e., 75 µg and 100 µg to ropivacaine on the quality of axillary brachial plexus block. MATERIAL AND METHODS After obtaining Ethics Committee approval (University of Health Sciences, Rohtak) and written informed consent, 75 American Society of Anesthesiologists physical status I-II patients undergoing elective upper limb surgery, including forearm, wrist and hand procedures, were prospectively enrolled. Depending upon the use and the dose of dexmedetomidine used with ropivacaine for axillary brachial plexus block, these patients were
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randomly assigned to three groups. Group R (n = 25) received 34 mL of 0.5% ropivacaine plus 1 mL of normal saline, Group RD75 (n = 25) received 34 mL of 0.5% ropivacaine plus 0.75 mL (75 µg) dexmedetomidine plus 0.25 mL of normal saline. Group RD100 (n = 25) received 34 mL of 0.5% ropivacaine plus 1 mL (100 µg) dexmedetomidine. Intravenous access was established and standard monitors (noninvasive arterial blood pressure [BP], electrocardiography and pulse oximetry) were attached. The operative arm was abducted and externally rotated. The elbow was flexed to 90°. The nerves were blocked in the following order: median, ulnar, radial and musculocutaneous nerve. Under all aseptic conditions, after palpating the axillary artery, a 22 gauge, 5 cm long, short-bevelled, teflon-coated nerve stimulator needle was inserted superior to it in the axilla where median nerve is located. Initially, the nerve stimulator was set to a pulse duration of 0.15 ms, current intensity of 2 mA, frequency of 2 Hz to localize proximity to plexus by observing the muscle stimulations in the forearm and hand. Further, the needle was advanced and current intensity was decreased until the visible muscle stimulation remained even at 0.5 mA. Stimulation of median nerve lead to wrist, 2nd and 3rd finger flexion and pronation. Stimulation of ulnar nerve (inferior to the artery) caused 4th and 5th finger flexion and thumb adduction. Stimulation of radial nerve (posterolateral to the artery) lead to arm and finger extension and supination. Ten milliliter of drug solution as per the group allocation was injected near each nerve. The musculocutaneous nerve was blocked in the substance of coracobrachialis muscle, its stimulation lead to arm flexion, at this point 5 mL of drug was injected and the needle was finally removed. Intensity of sensory block was assessed using a three point scale. Where scale 0 was taken as normal sensation, scale 1 as loss of sensation to pin prick and scale 2 as loss of touch sensation. Onset of sensory block (T2-T1) was defined as the time interval from drug administration (T1) to attainment of sensory block scale ≥1 (T2). Duration of sensory block (T3-T2) was defined as the interval between attainment of sensory block scale ≥1 (T2) and its regression to scale 0 (T3). Intensity of motor block was assessed by modified Bromage scale. Motor block scale 4 was taken as full power, 3 as reduced power but ability to move against resistance, 2 as inability to move against resistance but able to move against gravity, 1 as flicker of movement and 0 as no movement at all. Onset of motor block (T4-T1) was defined as the time interval from drug
ANESTHESIOLOGY administration (T1) to attainment of motor power score of ≤2 (T4). Duration of motor block (T5-T4) was defined as the interval between the attainment of motor block scale ≤2 (T4) and its regression to scale ≥3 (T5). Sedation was scored using a four point scale, where 1 depicted fully awake, 2 for drowsy but responsive to command, 3 for very drowsy but responsive to pain and 4 for unresponsiveness. Readiness to surgery (surgical anesthesia) was defined as a sensory score of ≥1 and motor score of ≤2. If this was not achieved, the case was excluded from the study. Sensory and motor block were evaluated every 5 minutes after drug administration up to 30 minutes or achievement of readiness to surgery, whichever was earlier. In case of pain during surgery, supplementary intravenous analgesia with 2 µg/kg-1 of fentanyl was administered. If the patient still complained of pain, general anesthesia was administered, and this case was considered as failure. Postoperative pain was assessed using visual analog scale (VAS) on a scale of 0 to 10. When VAS was equal to 4 or the patient demanded analgesia, injection diclofenac 75 mg was administered intramuscularly and this time was recorded (T6). Patient satisfaction was assessed using a two point scale, after enquiring from the patient about his/her willingness to have same anesthetic if ever operated again. 1 = (Good): “If ever operated again in the future, I want the same anesthetic”. 2 = (Bad): “If ever operated again in future, I want a different anesthetic”.
Statistical Analysis Demographic factors age and weight were compared across the groups through analysis of variance (ANOVA). The test statistic is p-value which was compared across
the three groups. The threshold was kept at 0.05. Sex distribution was compared as contingency tables through Fisher exact test. The observations of onset and duration of sensory and motor blocks were compared through ANOVA. Duration of analgesia and duration of surgery were also compared through ANOVA across the three groups. Hemodynamic parameters i.e., heart rate, BP were compared within the groups at different time frames with the baseline through ANOVA. These parameters were also compared across the groups at different time frames through ANOVA for intergroup comparisons. To compare the number of patients requiring supplemental fentanyl in the three groups, Fisher exact test was used for 3 × 3 contingency table analysis. Complications of hypotension and bradycardia among the three groups were compared using contingency table analysis through Fisher exact test. RESULTS Our study is the first of its kind, comparing the effect of two different doses of dexmedetomidine added to ropivacaine for axillary brachial plexus block in upper limb surgery. The three groups of this study were similar with regards to demographic parameters like age, weight and sex distribution. The time taken to administer the block and duration of surgery were also comparable in all the three groups (Table 1). Mean onset time of sensory block and motor block was found to be comparable in all the three groups. Groups RD75 and RD100 had significantly longer duration of sensory block, motor block and duration of analgesia than Group R, but the two groups i.e., RD75 and RD100 when compared with each other had no statistical difference (Table 2). Groups RD75 and RD100 had statistically significant higher sedation scores than the control Group R. Though the heart rate was comparable in all groups (Fig. 1), the groups RD75 and RD100 had significantly lower systolic BP (SBP) when compared
Table 1. Demographic Profile and Surgery Duration Group R (n = 25) (mean ± SD)
Group RD75 (n = 25) (mean ± SD)
Group RD100 (n = 25) (mean ± SD)
Age (years)
37.08 ± 14.42
35.20 ± 15.49
32.88 ± 11.88
Weight (kg)
72.00 ± 7.07
68.40 ± 7.46
70.80 ± 8.62
21/4
19/6
19/6
103.2 ± 61.83
125 ± 73.88
91.8 ± 33.26
Gender (male/female) Duration of surgery (minutes)
There is no statistically significant difference among the three groups with respect to demographic profile and surgery duration.
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ANESTHESIOLOGY Table 2. Sensory and Motor Block Onset, Block and Analgesia Durations Group R (n = 25) (mean ± SD)
Group RD75 (n = 25) (mean ± SD)
Group RD100 (n = 25) (mean ± SD)
8.36 ± 6.42
8.20 ± 4.30
7.20 ± 3.88
Onset time of motor block (minutes)
13.00 ± 10.12
11.40 ± 7.43
11.72 ± 6.59
Duration of sensory block (minutes)
477.12 ± 309.10
687.80 ± 304.72*
687.04 ± 307.62*
Duration of motor block (minutes)
519.48 ± 327.84
706.20 ± 292.36*
730.12 ± 297.13*
Duration of analgesia (minutes)
575.48 ± 323.88
764.00 ± 311.00*
818.44 ± 338.67*
8.84 ± 3.21
7.40 ± 3.27
8.36 ± 2.77
Onset time of sensory block (minutes)
Time taken to administer the block (minutes)
*p < 0.05 value significantly different when compared to the control Group R.
Group RD75
Group R
Group RD100
75 70 65 60 55 50 0 0
5
10
15
20
25
30
45
Group RD75
Group RD100
80 Diastolic BP (mmHg)
Heart rate (beats per second)
Group R
75 #
65
#
#
#
#
#
#
#
20
25
30
45
#
60 55
0
60
#
70
0
5
10
15
60
Time (minutes)
Time (minutes)
Figure 1. Graphical trends in heart rate in three groups over different time frames.
Figure 3. Graphical trends in diastolic BP in three groups over different time frames. #means
p < 0.05 value, significantly different when compared to the respective baseline value of that group.
Group R
Group RD75
Group RD100
Systolic BP (mmHg)
130 125 *#
120
*
115
*#
*#
*
*
20
25
*#
*#
*
*
30
45
#
110 0
0
5
10
15
60
Time (minutes)
Figure 2. Graphical trends in systolic BP in three groups over different time frames. *means p < 0.05 value, significantly different when compared to the control Group R at same time frame. #means
p < 0.05 value, significantly different when compared to the respective baseline value of that group.
to Group R at 15, 20, 25, 30 and 45 minutes (Fig. 2). However, the SBP in the two groups i.e., RD75 and RD100 were comparable to each other. SBP in Group RD100 decreased significantly from the baseline at 15, 20, 25, 30, 45 and 60 minutes. Mean diastolic BP (DBP)
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in the three groups were comparable (Fig. 3). However, intra-group variations in groups RD75 and RD100 showed decrease in BP from the baseline. The three groups were comparable with respect to supplementation with injection fentanyl, incidence of hypotension and bradycardia. All the patients except three were well-satisfied by this anesthetic method. These patients were the failure cases who required general anesthesia intraoperatively. DISCUSSION Peripheral nerve block is a common regional anesthetic technique aptly suited to a broad-spectrum of surgical, interventional and diagnostic procedures. Increasing the duration of peripheral nerve block to treat postoperative pain is a key issue in regional anesthesia. Ropivacaine is a comparatively new long-acting amino amide local anesthetic with longer duration of action, lower potential for cardiotoxicity and differential sensory motor blockade, making it better than racemic
ANESTHESIOLOGY bupivacaine. In an attempt to further increase the duration of the block, various adjuvants have been added to ropivacaine to prolong its action and to minimize the use of analgesics in the postoperative period.
in the axilla (musculocutaneous, radial, median, ulnar) were identified using peripheral nerve stimulator. In their study, the sensory and motor block onset times were shorter with addition of dexmedetomidine and the duration of blockade was longer.
Clonidine, an α2-AR agonist has been used with ropivacaine in peripheral nerve block, though the results have been somewhat less impressive probably because ropivacaine itself has an intrinsic vasoconstrictor effect.
In contrast to the study by Esmaoglu et al, where sensory and motor onset times decreased significantly with addition of dexmedetomidine; we did not observe any difference in the above parameters in our study amongst all three groups. This can be attributed to the differences in the mass and characteristic of local anesthetic used in the two studies. Esmaoglu et al used 40 mL of 0.5% levobupivacaine, whereas we used 35 mL of 0.5% ropivacaine. Ropivacaine has an intrinsic vasoconstrictor property, hence addition of dexmedetomidine which causes α2-AR-mediated vasoconstriction may fail to make a difference. The onset times in above study were delayed as compared to ours, even though they used a larger volume of drug. This may have been due to the differences in the endpoint taken for onset of sensory and motor block in these studies. Esmaoglu et al defined onset of sensory block as loss of sensation to touch, whereas the endpoint in our study was loss of sensation to pinprick, which precedes the former in chronology. Similarly, they defined onset of motor block as absence of voluntary movement, whereas the endpoint in our study was ability to move against gravity but inability to move against resistance.
Dexmedetomidine, a highly selective α2-AR agonist has recently been introduced in anesthesia practice. Its potential benefit as an adjuvant to local anesthetic in peripheral nerve block has been emphasized in few experimental studies. There have been four proposed mechanisms of action of α2-AR agonist in peripheral nerve blocks. These mechanisms include direct action on the peripheral nerve, centrally-mediated analgesia, α2B-AR-mediated vasoconstrictive effects and attenuation of the inflammatory response. Despite the fact that there is no α2-AR representation on peripheral nerves, there is prolongation of action by perineural administration of α2-AR agonist as an adjuvant to local anesthetics. This is attributed to blocking the so-called hyperpolarization-activated cation current (Ih current) which results in prolonged hyperpolarization of the nerve. Centrally, α2-AR agonists cause analgesia and sedation by inhibition of substance P release in the nociceptive pathway at the level of the dorsal root neuron and by activation of α2-AR in the locus coeruleus. Apart from the above mechanisms, clonidine may reduce systemic up-take of the perineurally deposited local anesthetic-clonidine mixture by means of α1receptor-mediated vasoconstriction (dexmedetomidine has a very limited effect on α1-adrenoceptors). Dexmedetomidine exhibits synergism with local anesthetics, prolonging their duration of action. So far, the clinical evidence for the use of dexmedetomidine as an adjuvant to local anesthetic for peripheral nerve blocks is limited to few animal studies and three human studies. Esmaoglu et al (2010) evaluated the effect of adding dexmedetomidine to levobupivacaine for axillary brachial plexus block in upper limb surgery. Forty milliliters of 0.5% levobupivacaine plus 1 mL of saline were administered to one group and in the other group 40 mL of 0.5% levobupivacaine plus 1 mL (100 µg) of dexmedetomidine were given. The four main nerves
As far as duration of block is concerned, our findings are in agreement to that of Esmaoglu et al. There was a marked increase in duration of analgesia in Group RD75 and Group RD100, as compared to Group R. These parameters were comparable in Group RD75 and Group RD100. Can it be due to ceiling effect, as has been shown by Jaakola while using dexmedetomidine intravenously; is difficult to ascertain in this study. This aspect needs to be evaluated further. Esmaoglu and colleagues reported significantly lower systolic and diastolic pressure, and heart rate in the group using dexmedetomidine as an adjuvant. In contrast, in our study though there was a decreasing trend in heart rate after administration of block in Group RD75 and Group RD100 patients, but it did not achieve statistical significance. Our results, with regard to BP, were in accordance to theirs, with significant decrease in SBP in groups RD75 and RD100 as compared to the control Group R, though DBPs were comparable in all three groups. Other than the above mentioned intergroup differences, there was a significant decrease in DBP from baseline in Group RD75 at 20-45 minutes
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ANESTHESIOLOGY interval and in Group RD100 at 15-60 minutes interval. These effects on heart rate and BP have been ascribed to direct vascular effects from α2-AR agonism combined with inhibition of cardiac sympathetic drive. Dexmedetomidine is known to cause dose-dependent bradycardia and hypotension. Though bradycardia and hypotension episodes did occur in few patients in our study, they were not statistically significant. When this study was planned, only two human studies using dexmedetomidine as an adjuvant perineurally were available, none used ropivacaine. During the conduct of this study, a study by Marhofer et al appeared in the literature, who conducted a study on 36 volunteers to investigate the effects of perineural or systemic dexmedetomidine as an adjuvant to ropivacaine in ultrasound-guided ulnar nerve block. All three groups received 3 mL of 0.75% ropivacaine. One group received 20 µg dexmedetomidine perineurally in addition to ropivacaine (RpD), second group received 20 µg dexmedetomidine systemically in addition to ropivacaine (RsD). They were compared to the control Group R, who received only ropivacaine. Similar to our findings, sensory onset time was not different between the study groups, but motor onset time was significantly faster in Group RpD when compared with the other study groups (Group RsD and Group R). The prolongation of blockade after perineural administration of dexmedetomidine (60%) was much more than its systemic administration (10%). Supplemental fentanyl (2 µg/kg-1) had to be administered intravenously for intraoperative pain in 12 patients. The three groups on statistical analysis were found to be comparable in receiving supplementation. Administration of dexmedetomidine leads to arousable sedation in patients. The sedation scores were significantly higher in groups with the drug i.e., Group RD75 and Group RD100 as compared to the control Group R. However, most of these patients were readily awakened from sleep by simply talking to them. Absorption of drug into the systemic circulation subsequent to perineural injection may be the cause for sedation. Dexmedetomidine is known to cause sedation by its action on α2-AR in the locus coeruleus, the predominant noradrenergic nucleus in the brain and an important modulator of vigilance. We observed high satisfaction rates to our credit because of the long duration of analgesia of ropivacaine and still longer when dexmedetomidine was added. All the patients except three were well-satisfied.
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LIMITATION The limitation of the present study was that the dose of dexmedetomidine (100 µg) used for peripheral nerve block was based on its previous use by Esmaoglu et al and a lower dose (75 µg) was arbitrarily chosen. We did not undertake a dose-response study to check whether still lower doses of dexmedetomidine would have yielded same or different results. Another limitation of our study was the unavailability of ultrasound, which is currently the gold standard in nerve localization. Larger sample size could have helped us validate our results more emphatically. CONCLUSION To conclude, addition of dexmedetomidine as an adjuvant to ropivacaine in axillary brachial plexus block extends the duration of sensory and motor block, and also prolongs the analgesia period. As of present scenario, only few studies in literature highlight the use of dexmedetomidine as an adjunct. Hence, more research work, on larger number of patients with lower doses of dexmedetomidine as an adjunct to local anesthetic is required to completely explore the potentials of this drug. SUGGESTED READING 1. De Jong RH. Axillary block of the brachial plexus. Anesthesiology. 1961;22:215-25. 2. Schroeder LE, Horlocker TT, Schroeder DR. The efficacy of axillary block for surgical procedures about the elbow. Anesth Analg. 1996;83(4):747-51. 3. McClure JH. Ropivacaine. Br J Anaesth. 1996;76(2):300-7. 4. Akerman B, Hellberg IB, Trossvik C. Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand. 1988;32(7):571-8. 5. Hickey R, Blanchard J, Hoffman J, Sjovall J, Ramamurthy S. Plasma concentrations of ropivacaine given with or without epinephrine for brachial plexus block. Can J Anaesth. 1990;37(8):878-82. 6. Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med. 1999;24(3):255-63. 7. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999;54(2):146-65. 8. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21(4):457-61. 9. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of
ANESTHESIOLOGY small-dose dexmedetomidine infusions. Anesth Analg. 2000;90(3):699-705. 10. Shukry M, Miller JA. Update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures. Ther Clin Risk Manag. 2010;6:111-21. 11. Ishii H, Kohno T, Yamakura T, Ikoma M, Baba H. Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord. Eur J Neurosci. 2008;27(12):3182-90. 12. Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology. 1996;84(4): 873-81. 13. Nelson LE, You T, Maze M, Franks NP. Evidence that the mechanism of hypnotic action in dexmedetomidine and muscimol-induced anesthesia converges on the endogenous sleep pathway. Anesthesiology 2001; 95:A-1368. 14. Groen GJ, Gielen MJ, Jack NT, Knape JT. At the cords, the pinkie towards: interpreting infraclavicular motor responses to neurostimulation. Reg Anesth Pain Med. 2004;29(5):505-7; author reply 507. 15. O’Donnell B, Riordan J, Ahmad I, Iohom G. Brief reports: a clinical evaluation of block characteristics using one milliliter 2% lidocaine in ultrasound-guided axillary brachial plexus block. Anesth Analg. 2010;111(3):808-10. 16. Morgan GE, Mikhail MS, Murray MJ. Peripheral nerve blocks. In: Morgan GE, Mikhail MS, Murray MJ (Eds.). Clinical Anaesthesiology. 4th Edition, New York: McGraw Hill; 2008. pp. 324-37.
18. Esmaoglu A, Yegenoglu F, Akin A, Turk CY. Dexmedetomidine added to levobupivacaine prolongs axillary brachial plexus block. Anesth Analg. 2010;111(6):1548-51. 19. Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol. 2011;27(3):297-302. 20. Brummett CM, Padda AK, Amodeo FS, Welch KB, Lydic R. Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat. Anesthesiology. 2009;111(5):1111-9. 21. Lönnqvist PA. Alpha-2 adrenoceptor agonists as adjuncts to Peripheral Nerve Blocks in Children - is there a mechanism of action and should we use them? Paediatr Anaesth. 2012;22(5):421-4. 22. Brummett CM, Norat MA, Palmisano JM, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology. 2008;109(3):502-11. 23. Obayah GM, Refaie A, Aboushanab O, Ibraheem N, Abdelazees M. Addition of dexmedetomidine to bupivacaine for greater palatine nerve block prolongs postoperative analgesia after cleft palate repair. Eur J Anaesthesiol. 2010;27(3):280-4. 24. Marhofer D, Kettner SC, Marhofer P, Pils S, Weber M, Zeitlinger M. Dexmedetomidine as an adjuvant to ropivacaine prolongs peripheral nerve block: a volunteer study. Br J Anaesth. 2013;110(3):438-42.
25. 17. Casati A, Danelli G, Baciarello M, Corradi M, Leone S, Di Cianni S, et al. A prospective, randomized comparison between ultrasound and nerve stimulation guidance 26. for multiple injection axillary brachial plexus block. Anesthesiology. 2007;106(5):992-6. ■■■■
Jaakola ML. Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth. 1994;6(3):204-11. Thompson GE, Brown DL. The common nerve blocks. In: Nunn JF, Utting JE, Brown BB (Eds.). General Anesthesia. 5th Edition, London: Butterworths; 1989. pp. 1068-9.
Breakthrough Technique for Spine and Thyroid Surgery A novel, less invasive technique may help clinicians to continuously assess laryngeal and vagus nerve function while patients are under general anesthesia during neurosurgery or otolaryngology procedures, suggests new research published in the July issue of Clinical Neurophysiology. The new technique makes use of a simple endotracheal tube, which simultaneously and continuously stimulates and monitors nerve responses.
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CARDIOLOGY
Role of Flavonoids in Prevention of Coronary Heart Disease and Other Chronic Diseases PRAGATI KAPOOR*, PANKAJ KUMARâ&#x20AC;
ABSTRACT Dietary flavonoids represent a diverse range of polymeric compounds that occur naturally in small quantities in plant foods. Flavonoids are present in significant amounts in fruits, vegetables, nuts and seeds, grain, herbs and beverages. These have been classified into seven subclasses as flavonols, flavones, flavanones, flavan-3-ols, isoflavones, anthocyanidins and proanthocyanidins. The physiological activities of flavonoids are diminished by factors such as lifestyles, age, sex, race and other disease states and interaction with drugs. They have a wide range of biological activities. They are antioxidants and thus may reduce the oxidation of low-density lipoprotein cholesterol and prevent atherosclerotic disease and lower the risk of developing coronary heart disease. They have been reported to have cardioprotective effects and are also beneficial in several chronic diseases. The potentially beneficial therapeutic effects of flavonoids are mainly ascribed to quercetin, the most potent antioxidant.
Keywords: Polymeric compounds, flavonoids, flavones, flavanones, chronic diseases, quercetin, antioxidant
P
lant flavonoids are widely distributed polyphenolic compounds from dietary sources and are well-established as antioxidants.1,2 Flavonoids are low molecular weight, lipid-soluble, aromatic compounds (phytochemicals) derived from fruits, vegetables, herbs, seeds and nuts and other plant components. The flavonoid group of compounds are classified into at least 10 different classes depending on their chemical structures though there are seven major subclasses based on specific structural differences namely flavonols, flavones, flavanones, flavan-3-ols (catechins), anthocyanidins, proanthocyanidins and isoflavones.3 They have wide variety of biological actions,4,5 are effective antioxidants because of their free radical scavenging properties and are chelators of metal ions.5 In vitro assays have demonstrated
*Assistant Professor Dept. of CTVS Nizam Institute of Medical Sciences, Hyderabad, Telangana â&#x20AC; Assistant Professor Dept. of Pharmacology Rohilkhand Medical College and Hospital, Bareilly, Uttar Pradesh Address for correspondence Dr Pankaj Kumar Assistant Professor Dept. of Pharmacology Rohilkhand Medical College and Hospital, Bareilly - 243 006, Uttar Pradesh E-mail: drpankajrkumar@yahoo.com
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that flavonoids that possess anti-inflammatory, antiallergic, antithrombotic, venotonic, antimicrobial and antineoplastic activities6 mediated by different mechanism.4,7 Some are estrogenic, others are antithyroidal and certain flavonoids can be mutagenic.7 The potential therapeutic utility of high dietary intake of flavonoids is based on the correlation that these compounds not only lowered risk of cardiovascular diseases (CVDs) but also the incidence of myocardial infarction and stroke,8,9 and have protective and potentially beneficial role in a variety of chronic illnesses namely rheumatoid arthritis, asthma, type 2 diabetes, etc.4 Knekt et al4 suggested a preventive role of flavonoids particularly quercetin in cases of coronary heart disease (CHD). Recent studies with significantly larger cohorts (1,000-90,000 participants), with follow-up periods of up to 11 years, have shown that dietary intake of flavonoids decreased risk of death from CVD,10,11 a protective effect against peripheral arterial occlusive disease12 and prevention of CHD.13 However, several epidemiological studies demonstrated no association between dietary intake of flavonols (e.g. quercetin) and ischemic heart disease,14 or plasma antioxidant levels.15 Clinical trials have demonstrated the effects of dietary flavonoids on CVD risk factors,16,17 post-thrombotic syndrome,18 atherosclerosis17 and vascular health.19,20 Additionally, diet rich in plant foods lowers the risk of developing CHD.21
CARDIOLOGY There is a growing appreciation that free oxygen radicals are involved in several pathologic conditions22 and that damaging oxidative processes are a common biochemical link between otherwise pathophysiologically distinct diseases.23 For example, early atherosclerotic lesions are promoted by low-density lipoprotein (LDL) particles that are oxidatively modified,24,25 and oxidative damage to nucleic acids may lead to carcinogenesis.26 Biochemical composition of flavonoids, their range of pharmacological and physiological effects, potential toxicities and their health benefits are being discussed. FLAVONOIDS STRUCTURE AND STRUCTURE ACTIVITY RELATIONSHIP Plant flavonoids are polyphenolic, low molecular weight, aromatic compounds which have a common structure based on 2-phenylbenzo-gamma-pyrane i.e., two benzene rings (A and B rings) joined by a third pyrane ring (C-ring). Polyphenols include several classes of compounds and amongst polyphenols, flavonoids constitute the most important single group comprising more than 5000 compounds.27 Flavonoids are antioxidants, their free radical scavenging activities28-30 are dependent on electron donating hydroxyl group substitutions on the aromatic B ring and heterocyclic C ring.30,31 The C2-C3 doublebond conjugated to a C4 carbonyl group on the C ring is responsible for antioxidant activity through formation of an electron delocalization system.30,31 Besides, functional groups conjugated to the flavonoid structure through metabolism also affect the antioxidant potential of these compounds. Substitution of the C3 and C4 positions on the C and B rings with a glucuronide group, respectively was shown to diminish scavenging activity, but only a negligible decrease was observed for a glucuronide group at the C7 position on the A ring.32 Variations in the C and B ring hydroxyl group substitutions, and metabolically added sulfate and methyl groups, determine the potency of these compounds for inhibition of platelet signaling and function.33 The C ring C2-C3 double bond and at least two benzene rings are required for potent inhibition of platelet function.8 Evidences suggest polyphenols display a degree of selectivity. Flavonoids and their biological metabolites bind to the major plasma carrier protein, human serum albumin, with different affinities. Erythrocytes internalize flavonols and flavones to varying degrees.34 In short, structure activity relationship of flavonoids will pave way to construct analogs with high potency and
selectivity, and in developing a new generation of flavonoid-based inhibitory agents having better efficacy and tolerability compared to existing antiplatelet drugs. To understand flavonoid inhibitory mechanism requires exploration of molecular interactions of flavonoids with kinases. Flavonoid ring systems and their hydroxyl substitution are involved profoundly in binding of these compounds to Src - family kinases (HCK),35 lipid kinases (PI3KÎł)36 and serine/threonine kinases (P1M1).37 The translation of flavonoids into more potent and selective small molecules of potential therapeutic utility are being pursued. Quercetin is the main flavonoid used as a template for drug design. Analogs of quercetin are being synthesized which are more potent than quercetin for inhibition of PI3K, and analogs of isoflavonone and isoflavanone compounds are being used as templates for the design of more potent analogs for inhibiting interleukin activity.38 Flavonoids confer a great scope for creating novel kinase inhibitors, which are clinically safer and more selective in respect to antiplatelet therapy. DISTRIBUTION OF FLAVONOIDS Flavonoids are widely distributed in plant kingdom. Phenolic rich crops include grapes, olives and heavily pigmented vegetables. Other plants rich in phytochemicals include cabbage and broccoli that are excellent sources of indoles, dithiolthiones, isothiocyanates and chlorophyllins. Legumes (soybeans, peanuts, beans and peas) contain flavonoids, isoflavonoids isoflavones and other polyphenols. These compounds may reduce risk of atherosclerosis,39 since these favorably affect plasma lipids40 and inhibit platelet aggregation. Other dietary sources rich in flavonoids are apple, onion, oranges, etc. Tea and red wine are also major sources of flavonoids.41 The major flavonoids include quercetin, kaempferol, myricetin, naringenin and hesperetin (Table 1).
Physiological and Pharmacological Actions Most researcher are actively pursuing role of phytochemicals regarding physiological and pharmacological effects in widely consumed foods and beverages such as fruits, vegetables, legumes, chocolate, tea, wine and olive oil.42 Owing to differences in their chemical structure, bioavailability, distribution and metabolism different flavonoid compounds may have different effects on human health. The physiological actions of flavonoids are reduced by factors such as lifestyles, age, sex, race, other disease states and drug interactions.43-45
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CARDIOLOGY Table 1. Flavonoids Subclasses, Food Sources and Active Compounds Flavonoid subclass
Major dietary sources
Compounds
Flavonols
Onions, broccoli, tea and various fruits (apples)
Quercetin, kaempferol, myricetin and isorhamnetin
Flavones
Herbs (especially parsley), celery and chamomile tea Tangeretin is present tangerines and some other citrus
Apigenin, luteolin, tangeretin
Flavanones
Citrus fruits including oranges and grape fruit, lemons
Naringenin, hesperetin, eriodictyol
Flavan-3-ols or flavonols
Cocoa or dark chocolate, apples, grapes or red wine and green tea, black tea
(+)- Catechin, (-)- epicatechin and their polymers, tea catechins such as epigallocatechin, gallate
Anthocyanidins or and anthocyanins
Colored berries and other fruits, especially cranberries, black currants and blue berries, raspberries and red wine
Cyanidin, delphinidin, pelargonidin, malvidin and petunidin
Isoflavones or phytoestrogens
Soy products including fermented products e.g., tofu, tempeh and soy protein isolate, soy milk
Daidzein, genistein and glycitein
Proanthocyanidin
Proanthocyanidins (apples, chocolate, seeded grapes)
Monomers, dimmers, trimers, 4-6 mers, 7-10 mers and polymers diadzein, genistein, glycitein
As Antioxidants Flavonoids are well-established antioxidants owing to their free radical scavenging properties and being chelators of metal ions, protecting tissues against free oxygen radicals and lipid peroxidation. They reduce oxidation of LDL cholesterol, thus reduce development of atherosclerosis.25 The differences in antioxidative potential of different flavonoids subclasses depend on their chemical structures and these may cast different effects on human health. Protection Against Free Oxygen Radicals and Lipid Peroxidation Flavonoids protect tissues against free oxygen radicals and lipid peroxidation, former being involved in several pathological conditions.22 Involvement of free oxygen radicals has been suggested at different stages of cancer development,26 and contribute to the autoimmune destruction of beta cells leading to diabetes46 and impaired insulin action.47 Reactive oxygen species (ROS) may act as mediators of inflammatory damage in asthma,48 and rheumatoid arthritis,49 additionally, free radicals are involved in the process leading to cataract development.50 Thus, apart from antioxidant property, flavonoids may also be activated by mechanisms that are not directly dependent on their antioxidant properties.51,52 Effects on Phosphorylation and Kinases Red wine containing high levels of flavonoids, quercetin and catechin have been shown to inhibit phosphorylation of the serine/threonine kinases, p38
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mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2(ERK1/2) and protein kinase B (PKB)/AKT in vascular smooth muscle cells,53 and endothelial cells.54 Polymeric catechin, epigallocatechin gallate has also been shown to inhibit p38 MAPK and ERK 1/2 phosphorylation in platelets55 and tyrosine kinases in mast cells.56 Flavonoids such as quercetin, catechin and apigenin also inhibit the activities of tyrosine kinases (Fyn, Lyn, Syk)33,57 lipid kinases (P13KÎł)57 besides phosphorylation of the Fc-RÎł-chain,57 phospholipase CÎł233,57 and the membrane protein, linker for activation of T (LAT) cells,57 in platelets. The green tea flavonoid, epigallocatechin-3-gallate and the isoflavone, genistein inhibited phosphodiesterases (PDEs) and Rac1 protein concerned with platelet activation and in other cell types.58,59 Furthermore, platelet function may also be inhibited by flavonoidsmediated increases in nitric oxide (NO) production.60 and blocking of pathways leading to mobilization of calcium from intracellular stores.57,61 Flavonoids are nonspecific broad-spectrum inhibitors of kinases, the activity and selectivity of these agents is dependent on their structure. Inhibition of kinase activity by flavonoids is responsible for anti-inflammatory, antithrombotic and antiproliferative properties.6 Thus, flavonoids may create novel kinase inhibitors, which are clinically safer and more selective particularly applicable to antiplatelet therapy. Two clinical strategies for the use of flavonoids as antiplatelet therapy are firstly, combining these agents with existing antiplatelet agents and secondly,
CARDIOLOGY to investigate potential synergistic inhibitory effects on platelet function since these compounds potentiate subinhibitory concentrations of aspirin.62 Disruption of Cell Signaling Flavonoids disrupt cell signaling by decreasing the fluidity of the lipid bilayer by disrupting proteinprotein interactions63,64 and by binding to cell surface receptors.65,66 Quercetin binds to thromboxane A2 (TxA2),65 adenosine diphosphate receptors66 and enhances the hypotonic integrity of erythrocytes after binding to their membranes.64 Flavonoids may influence, intracellular signaling enzymes such as kinases once internalized by cells.33,34,67 Quercetin and its metabolite tamarixetin are internalized by platelets and megakaryocytic cells.33 Modifications of Cytoskeletal Proteins Including Tubulin and Actin Flavonoids causes modifications of cytoskeletal proteins like tubulin68 and actin69 by blocking binding sites on the structures of cytoskeletal proteins and may exhibit inhibitory activities. Both tubulin and actin mediate platelet degranulation.70 Inhibition of Lipid Biosynthesis Pathways Flavonoids may suppress pathways of lipid biosynthesis and of very low-density lipoprotein (VLDL) production in cultured hepatocytes. Additionally, flavonoids may induce neutral lipid hydrolysis from lipid stores through PDE inhibition in adipose tissues and liver.59 Effect on Platelet Aggregability These effects of flavonoids are attributed to competitive inhibition of cyclic nucleotide PDE, an increase in cyclic adenosine monophosphate (cAMP) level and subsequent activation of protein kinase A (cAMP-dependent protein kinase).59 Flavonoids cause reduction of platelet function by working as pro-oxidants to enhance NO.60 Besides, these agents may also inhibit platelet function by inhibiting ROS production,28,71 binding to cell surface receptors,65,66 modifying structural proteins and disrupting cell membrane integrity.64 The antioxidant and pro-oxidant28,60,70 activities of flavonoids and their ability to bind to cell membrane64 and structural proteins,68,69 may lead to generation of small-molecule inhibitors. Effect on Blood Pressure Chronic consumption of black tea, red wine or grapes and other flavonols did not show significant effects on systolic or diastolic blood pressure (BP), but chronic
intake of chocolate and cocoa reduced both systolic (by 5.88 mmHg) and diastolic (by 3.30 mmHg) BP.72 The effect of different soy sources on BP are varied. The data from isoflavone extracts suggest a reduction in BP but no effect on diastolic BP.72 Acute consumption of black tea increased systolic and diastolic BP.72 Soy protein isolate (but not other soy products or components) significantly reduced diastolic BP.72 Effect on Flow-mediated Dilatation Different flavonoid groups have different effects on flow-mediated dilatation (FMD; a measure of endothelial function which is a predictor of cardiovascular events).72 Acute and chronic chocolate intake increased FMD.72 Daily consumption of 50 g dark chocolate increases FMD by 4% acutely and by 1.4% chronically and in turn may decrease Framingham risk by 1%.72 However, high proportions of these studies were funded by chocolate industries. In short, effects on FMD are mixed. Soy protein isolate (SPI) and isoflavone extract group showed no statistically significant chronic effects on FMD.72 Similar observations were recorded in respect to chronic effects of red wine or grape and other flavonols.72 Flavonols rather caused a reduction in FMD. Regarding anthocyanins, flavonones, green tea and soy foods, no published data on potential FMD effects are available. None of the flavonoid subgroups showed any significant effects on glyceryl trinitrate (GTN)mediated FMD, a measure of endothelium-independent dilatation. Flavonoids probably influence FMD through effects on the acute response cell-signaling pathways. Effect on LDL and HDL Cholesterol Flavonoids are antioxidants, thus reduce the oxidation of LDL cholesterol, which is thought to be involved in the development of atherosclerosis.25 The available evidences indicate that anthocyanins, black tea, chocolate and cocoa, red wine, grape, other flavonols, flavonoid mixtures, soy foods and isoflavones extracts have no effect on LDL concentrations, though green tea significantly decreased LDL.72 Green tea, red wine or grapes, soy foods and those of chocolate and cocoa, and isoflavone extracts have no effects on high-density lipoprotein (HDL) cholesterol.72 Increased plasma antioxidant capacity and increased resistance of LDL to chemically-induced oxidation has been recorded following wine intake, conversely negative results and mixed results in vivo studies, as in case of tea have also been reported.42 It is noteworthy that several studies have failed to note any difference among different alcoholic beverages with respect to their protective effects on cardiovascular system.
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CARDIOLOGY Since several phenolic molecules exert interesting biological activities, these may be classed as pharmacological hence contribution of flavonoids should be explored in these respect too. The potential beneficial effects of flavonoids were mainly ascribed to quercetin but also in some cases to kaempferol, myricitin, hesperetin and naringenin. Several studies support the hypothesis that flavonols and flavones protect against chronic diseases.4
endothelial function, inhibition of platelet activity and subsequent thrombosis in stenosed canine coronary arteries. Quercetin (apples, and onions are important sources) showed a cardioprotective role in Finnish diet. Two previous studies reported no evidence of cardioprotective effect of tea.14,43 There exists a great body of evidence to indicate that a diet rich in plant foods lowers the risk of developing CHD.21
Effect on Total Mortality
No association was found between total flavonoid intake and stroke mortality.3 The incidence of cerebrovascular disease leading to hospitalization or death was lower at higher intake of kaempferol, hesperetin and naringenin4 but not of quercetin.73 Dietary sources rich in these flavonoids included orange, white cabbage and grape fruits, and these showed inverse association with (CVD) occurrence.4 Apple intake too was inversely associated with thrombotic stroke.4 However, two other studies failed to find any association between flavonol and flavone intake and stroke mortality.74,75
A large prospective study in postmenopausal women with 16 years of follow-up showed that dietary intake of food rich in anthocyanin and flavonones were associated with lower risk of all causes mortality, death due to CHD and death due to CVD.3 Food items such as apples, pears, strawberries, red wine, chocolate and bran were associated with lower CHD and total CVD mortality.3,4 However, studies of flavonoid intake and mortality have also been inconsistent.4 Intake of flavonols and tea decreased CHD mortality.9 Mink et al3 did not observe decrease risk of CHD mortality. Grape fruit a major source of flavanones, was associated with a lower risk of CHD mortality.3 Knekt et al4 have observed that persons with higher total intake of flavonoids tended to have lower total mortality. Mortality from Ischemic Heart Disease Knekt et al4 reported an inverse association between flavonoid intake and subsequent occurrence of ischemic heart disease (IHD). IHD mortality tended to be lower at higher quercetin and kaempferol intakes.4 Of the dietary sources rich in flavonoids, apples, pear, red wine and onion intake are significantly associated with decrease in IHD mortality.3,4 Grape fruit has been associated with lower risk of CHD mortality3 but not with broccoli intake.3 Rimm et al43 found no association between apple intake and CHD mortality. Cardioprotective Effects Besides antioxidant potential, other probable mechanisms by which flavonoids exert cardioprotective effects include anti-inflammatory action, improvement in endothelial function, inhibition of platelet aggregation and induction of apoptosis. Flavonoids have potential cardioprotective properties, but epidemiological evidences of the cardiovascular effects of higher dietary intake of flavonoids are contradictory with some studies supporting4,9 and some not supporting,14,43 thus suggesting that epidemiological studies results are not conclusive. Other cardioprotective properties suggested for red wine and grape fruit juice include improved
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Cerebrovascular Diseases
Risk of Cancer The total cancer incidence was significantly lower at higher quercetin intake.4 Probably oxidative damage to nucleic acids may have an important role in carcinogenesis. Breast cancer and lung cancer76 risk was lower at higher quercetin intake, whereas prostate cancers risk was lower at higher myricetin intake.4 However, no significant associations were observed between flavonoid intake and occurrence of cancers of the stomach, colorectum or urinary organs.4 The studies of cancers with flavonoids have also given contradictory results, yet there is a strengthening of association between quercetin and lung cancer particularly in nonsmokers,4 and that apple intake was strongly associated with lower risk of lung cancer. Effect on Chronic Diseases Associated with Oxidative Stress ÂÂ
Type 2 diabetes: Higher quercetin and myricetin intakes were associated with lower risk of type 2 diabetes. The dietary sources rich in flavonoids, apple and berry intakes exhibited the strongest associations.4
ÂÂ
Rheumatoid arthritis: A higher intake of kaempferol is related to a high risk of rheumatoid arthritis but was not so with quercetin. Thus, intake of white cabbage was strongly associated with an increase in rheumatoid factor positive disease.4 ROS have been suggested as mediators of inflammatory damage in joints in rheumatoid arthritis.49
CARDIOLOGY ÂÂ
ÂÂ
Cataract: Even a high total intake of flavonoids did not significantly lower the cataract incidence, but an elevated risk of cataract was noted in the highest quartile of hisperetin intake.4 Probably, the oxidation of lens proteins by free radicals play an important role in the process leading to cataract.50 Asthma: A higher total intake of flavonoids lowered the incidence of asthma. This association was due to quercetin, hesperetin and naringenin.4 The strongest associations were noted for apple and orange intake.4 ROS have also been implicated as mediators of inflammatory damage in asthma.48
CONCLUSION Antioxidant flavonoids do exert a cardioprotective effects by preventing oxidization of LDL. The oxidizability of LDL is often employed as a biomarker of phytochemical effects. Healthful foods provide a mixture of bioactive micronutrients that probably are implicated for cardioprotective effects including CHD. Moreover, dietary intake of flavonoids lowers the risk of CHD and some chronic diseases. Flavonones, anthocyanidins and certain food items rich in flavonoids are responsible for reduced risk of death due to CHD, CVD and all-cause mortality. These compounds exhibited great scope for creating novel kinase inhibitors and the development of new generation of flavonoid based inhibitory agents to overcome the problems associated with existing antiplatelet agents. REFERENCES 1. Perron NR, García CR, Pinzón JR, Chaur MN, Brumaghim JL. Antioxidant and prooxidant effects of polyphenol compounds on copper-mediated DNA damage. J Inorg Biochem. 2011;105(5):745-53. 2. Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 2011;82(4):513-23. 3. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85(3):895-909.
7. Das A, Wang JH, Lien EJ. Carcinogenicity, mutagenicity and cancer preventing activities of flavonoids: a structuresystem-activity relationship (SSAR) analysis. Prog Drug Res. 1994;42:133-66. 8. Wright B, Spencer JP, Lovegrove JA, Gibbins JM. Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs. Cardiovasc Res. 2013;97(1):13-22. 9. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993;342(8878):1007-11. 10. McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R, Dwyer JT. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr. 2012;95(2):454-64. 11. Mursu J, Voutilainen S, Nurmi T, Tuomainen TP, Kurl S, Salonen JT. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr. 2008;100(4):890-5. 12. Lagiou P, Samoli E, Lagiou A, Skalkidis Y, Katsouyanni K, Petridou E, et al. Flavonoid classes and risk of peripheral arterial occlusive disease: a case-control study in Greece. Eur J Clin Nutr. 2006;60(2):214-9. 13. Mennen LI, Sapinho D, de Bree A, Arnault N, Bertrais S, Galan P, et al. Consumption of foods rich in flavonoids is related to a decreased cardiovascular risk in apparently healthy French women. J Nutr. 2004;134(4):923-6. 14. Hertog MG, Sweetnam PM, Fehily AM, Elwood PC, Kromhout D. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr. 1997;65(5):1489-94. 15. van der Gaag MS, van den Berg R, van den Berg H, Schaafsma G, Hendriks HF. Moderate consumption of beer, red wine and spirits has counteracting effects on plasma antioxidants in middle-aged men. Eur J Clin Nutr. 2000;54(7):586-91. 16. Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB, et al. Effects of chocolate, cocoa, and flavan3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr. 2012;95(3):740-51.
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34. Fiorani M, Accorsi A, Cantoni O. Human red blood cells as a natural flavonoid reservoir. Free Radic Res. 2003;37(12):1331-8. 35. Sicheri F, Moarefi I, Kuriyan J. Crystal structure of the Src family tyrosine kinase Hck. Nature. 1997;385(6617):602-9. 36. Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell. 2000;6(4):909-19. 37. Holder S, Zemskova M, Zhang C, Tabrizizad M, Bremer R, Neidigh JW, et al. Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase. Mol Cancer Ther. 2007;6(1):163-72. 38. Thanigaimalai P, Le Hoang TA, Lee KC, Sharma VK, Bang SC, Yun JH, et al. Synthesis and evaluation of novel chromone analogs for their inhibitory activity against interleukin-5. Eur J Med Chem. 2010;45(6):2531-6. 39. Howard BV, Kritchevsky D. Phytochemicals and cardiovascular disease. A statement for healthcare professionals from the American Heart Association. Circulation. 1997;95(11):2591-3. 40. Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29(2):95-120. 41. Hollman PC, Feskens EJ, Katan MB. Tea flavonols in cardiovascular disease and cancer epidemiology. Proc Soc Exp Biol Med. 1999;220(4):198-202. 42. Visioli F, Borsani L, Galli C. Diet and prevention of coronary heart disease: the potential role of phytochemicals. Cardiovasc Res. 2000;47(3):419-25. 43. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med. 1996;125(5):384-9. 44. Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68(5):468-77. 45. Lilja JJ, Juntti-Patinen L, Neuvonen PJ. Orange juice substantially reduces the bioavailability of the betaadrenergic-blocking agent celiprolol. Clin Pharmacol Ther. 2004;75(3):184-90. 46. Oberley LW. Free radicals and diabetes. Free Radic Biol Med. 1988;5(2):113-24. 47. Ceriello A. Oxidative stress and glycemic regulation. Metabolism. 2000;49(2 Suppl 1):27-9. 48. Greene LS. Asthma and oxidant stress: nutritional, environmental, and genetic risk factors. J Am Coll Nutr. 1995;14(4):317-24. 49. Darlington LG, Stone TW. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br J Nutr. 2001;85(3):251-69. 50. Davies KJ. Protein oxidation and proteolytic degradation. General aspects and relationship to cataract formation. Adv Exp Med Biol. 1990;264:503-11.
CARDIOLOGY 51. Rice-Evans CA, Miller NJ, Paganga G. Structureantioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20(7):933-56. Erratum in: Free Radic Biol Med 1996;21(3):417. 52. Keys A. Mediterranean diet and public health: personal reflections. Am J Clin Nutr. 1995;61(6 Suppl):1321S-1323S. 53. Oak MH, Chataigneau M, Keravis T, Chataigneau T, Beretz A, Andriantsitohaina R, et al. Red wine polyphenolic compounds inhibit vascular endothelial growth factor expression in vascular smooth muscle cells by preventing the activation of the p38 mitogenactivated protein kinase pathway. Arterioscler Thromb Vasc Biol. 2003;23(6):1001-7. 54. Kobuchi H, Roy S, Sen CK, Nguyen HG, Packer L. Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway. Am J Physiol. 1999;277(3 Pt 1):C403-11. 55. Lill G, Voit S, Schrör K, Weber AA. Complex effects of different green tea catechins on human platelets. FEBS Lett. 2003;546(2-3):265-70. 56. Maeda-Yamamoto M, Inagaki N, Kitaura J, Chikumoto T, Kawahara H, Kawakami Y, et al. O-methylated catechins from tea leaves inhibit multiple protein kinases in mast cells. J Immunol. 2004;172(7):4486-92. 57. Hubbard GP, Stevens JM, Cicmil M, Sage T, Jordan PA, Williams CM, et al. Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J Thromb Haemost. 2003;1(5):1079-88.
63. Rawel HM, Meidtner K, Kroll J. Binding of selected phenolic compounds to proteins. J Agric Food Chem. 2005;53(10):4228-35. 64. Chaudhuri S, Banerjee A, Basu K, Sengupta B, Sengupta PK. Interaction of flavonoids with red blood cell membrane lipids and proteins: antioxidant and antihemolytic effects. Int J Biol Macromol. 2007;41(1):42-8. 65. Guerrero JA, Lozano ML, Castillo J, Benavente-García O, Vicente V, Rivera J. Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost. 2005;3(2):369-76. 66. Jacobson KA, Moro S, Manthey JA, West PL, Ji XD. Interactions of flavones and other phytochemicals with adenosine receptors. Adv Exp Med Biol. 2002;505:163-71. 67. Fiorani M, Accorsi A. Dietary flavonoids as intracellular substrates for an erythrocyte trans-plasma membrane oxidoreductase activity. Br J Nutr. 2005;94(3):338-45. 68. Gupta K, Panda D. Perturbation of microtubule polymerization by quercetin through tubulin binding: a novel mechanism of its antiproliferative activity. Biochemistry. 2002;41(43):13029-38. 69. Böhl M, Czupalla C, Tokalov SV, Hoflack B, Gutzeit HO. Identification of actin as quercetin-binding protein: an approach to identify target molecules for specific ligands. Anal Biochem. 2005;346(2):295-9. 70. Cerecedo D, Stock R, González S, Reyes E, Mondragón R. Modification of actin, myosin and tubulin distribution during cytoplasmic granule movements associated with platelet adhesion. Haematologica. 2002;87(11):1165-76.
58. Zhang Y, Han G, Fan B, Zhou Y, Zhou X, Wei L, et al. Green tea (-)-epigallocatechin-3-gallate down-regulates VASP expression and inhibits breast cancer cell migration and invasion by attenuating Rac1 activity. Eur J Pharmacol. 2009;606(1-3):172-9.
71. Pignatelli P, Pulcinelli FM, Celestini A, Lenti L, Ghiselli A, Gazzaniga PP, et al. The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr. 2000;72(5):1150-5.
59. Peluso MR. Flavonoids attenuate cardiovascular disease, inhibit phosphodiesterase, and modulate lipid homeostasis in adipose tissue and liver. Exp Biol Med (Maywood). 2006;231(8):1287-99.
72. Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;88(1):38-50.
60. Freedman JE, Parker C 3rd, Li L, Perlman JA, Frei B, Ivanov V, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001;103(23):2792-8.
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61. Deana R, Turetta L, Donella-Deana A, Donà M, Brunati AM, De Michiel L, et al. Green tea epigallocatechin-3gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists. Thromb Haemost. 2003;89(5):866-74.
74. Yochum L, Kushi LH, Meyer K, Folsom AR. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol. 1999;149(10):943-9. 75. Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Stroke. 2000;31(10):2301-6.
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ENDOCRINOLOGY
Mauriac Syndrome Presenting as Primary Amenorrhea in a Case of Type 1 Diabetes Mellitus MEET M THACKER*, PRATIK VORA†, MIHIR THACKER‡, MANISH N MEHTA#
ABSTRACT Type 1 diabetes mellitus (T1DM) is a common occurrence and Mauriac syndrome is a well-documented complication of poorly controlled T1DM. It usually presents with hepatomegaly due to hepatic glycogen deposition, pubertal and growth delay, hypogonadism, dyslipidemia, protuberant abdomen, cushingoid features and elevated transaminases. We present here a case of an adolescent female with T1DM who presented with primary amenorrhea with cushingoid facies and poorly controlled diabetes taking premix insulin. With adequate glycemic control, the metabolic abnormalities were reversed and she had menarche at the age of 21 years.
Keywords: Diabetes mellitus, type 1 diabetes, complications of diabetes, Mauriac syndrome
P
oorly controlled diabetes is a frequent problem in developing countries like India, leading to many complications related to inadequate glycemic control and Mauriac syndrome is one of them. Mauriac syndrome complicates type 1 diabetes mellitus (T1DM) and includes short stature, glycogen laden enlarged liver leading to hepatomegaly, dyslipidemia, growth maturation and pubertal delay, moon facies, protuberant abdomen and proximal muscle wasting and it is also frequently associated with other microvascular complications like retinopathy and nephropathy.1,2
Commonly seen in children, adolescent and teens, it occurs equally in both sexes, and usually is seen in patients on plain insulin or premix insulin and with poor control of diabetes mellitus. With adequate control of blood sugar and with the advent of longer acting basal insulin, the incidence of this syndrome has been decreasing in the present era. With good glycemic control, most of the manifestations of this syndrome can be reversed; thus making a prompt diagnosis and effective and timely intervention is important.3
*Senior Resident †Second Year Resident ‡First Year Resident #Professor and Head Dept. of Medicine, Shri MP Shah Govt. Medical College, Jamnagar, Gujarat Address for correspondence Dr Meet M Thacker 36, Vardhaman Nagar, New Anjar, Anjar, Kutch, Gujarat E-mail: drmeetthacker@gmail.com
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CASE REPORT Ms S, a 19-year-old unmarried female was admitted in our ward with poorly controlled diabetes. A known case of T1DM since the age of 8 years, she was in follow-up of Pediatrics Department till 15 years of age and had no medical contact for the last 3 years. She was taking premix insulin (30:70 combination of regular insulin and NPH insulin) in the dose of 20 units in the morning and 12 units at night for the last 3 years. Upon admission, patient had a blood sugar (random) of 450 g/dL and urine had +3 sugar with no ketones by dipstick method. She denied any history of fever, nausea, vomiting, abdominal pain, burning micturition, etc. On general examination, she had stunted growth with a height of 134 cm (<95 percentile) and weight of 42 kg. General examination was also significant for ‘moonlike’ face (Fig. 1), protuberant, globular abdomen and less developed secondary sexual characteristics like sparse axillary and pubic hair. Breast development was Tanner’s stage II. Upon enquiry, she gave a history of primary amenorrhea. Blood and urine investigations on admission showed serum creatinine of 1.2 mg/dL, blood urea of 32 mg/dL, hemoglobin of 8.4 g/dL, total count of 11,400/μL. Urine sugar was +3 and urinary ketones absent by dipstick; 24 hours urinary protein excretion was 492 mg/24 hours. She had a glycosylated hemoglobin (HbA1c) of 12.2% suggesting markedly impaired glycemic control. Her thyroid function tests were within normal range. Lipid profile showed a total
ENDOCRINOLOGY
Figure 1. Characteristic moon-like face.
cholesterol of 320 mg/dL, low-density lipoprotein (LDL) was 170 mg/dL and triglycerides were 270 mg/dL. Subsequent evaluation by ultrasound of abdomen revealed hepatomegaly, hypoplastic uterus and evidence of renal parenchymal disease (loss of corticomedullary differentiation in bilateral kidneys). Fundoscopy revealed Grade 2 nonproliferative diabetic retinopathy. Thus, she was a case of poorly controlled T1DM, with nephropathy, retinopathy, hepatomegaly, characteristic moon-like face and primary amenorrhea. Liver biopsy was also done, which showed characteristic glycogen deposition and steatosis (Fig. 2), confirming the diagnosis of Mauriac syndrome. The patient was subsequently put on a basal-bolus regimen with insulin glargine at bedtime and three doses of plain insulin before three major meals. She was also counseled about adequate dietary restriction and a strict compliance was ensured. After 6 months of strict adherence to basal-bolus regimen and ensuring dietary and drug compliance, her HbA1c fell to 8.0% and thereafter was constantly maintained around 7-7.5%. With this strict control, after 2 years, she had her menarche at the age of 21 years and also showed improvement of growth as well as regression of hepatomegaly and other metabolic abnormalities including dyslipidemia.
Figure 2. H&E stained liver biopsy at high and low magnification.
DISCUSSION Mauriac syndrome was first described by Mauriac in 1930 in children with T1DM presenting with clinical features of growth failure, maturation delay, hepatomegaly and abdominal distension.4 This syndrome is related to poorly controlled insulin-dependent diabetes of long duration. With improved patient care and the use of longer acting basal insulin, the incidence of this syndrome has become unusual and severe growth failure or pubertal delay is rare in juvenile diabetic patients.5,6 Other clinical features of this syndrome consist of dyslipidemia, cushingoid facies, elevated liver transaminases, glycogen deposition in the liver and delayed maturation. The pathogenesis of Mauriac syndrome is not clear but thought to be multifactorial. The features of Mauriac syndrome are mostly related to fluctuating levels of glucose and insulin with both
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ENDOCRINOLOGY periods of underinsulinization and overinsulinization contributing to the presentation. Inadequate glucose to the tissues, decreased insulin-like growth factor 1 (IGF-1), growth hormone (GH) levels, hypercortisolism and resistant or defective hormone receptor action contribute to stunted growth and delayed puberty. The periods of supraphysiological levels of insulin are associated with glycogen deposition in the liver leading to hepatomegaly.7,8 Blood glucose passively enters the hepatocytes in which glycogen synthesis is promoted by high cytoplasmic glucose concentration reliant on the presence of insulin. Glycogen is then trapped within the hepatocytes as a result of a vicious cycle of hyperglycemia and insulin treatment.9 Poor glycemic control due to hypoinsulinemia leads to lipolysis and ketone liberation. Ketosis activates cortisol synthesis promoting the release of fatty acids and hyperglycemia.10 Liver biopsy is helpful to confirm the diagnosis of Mauriac syndrome. Histologic features are characterized by large, swollen, glycogen-laden hepatocytes and glycogenated nuclei without significant fatty change, inflammation, lobular spotty necrosis or fibrosis.9 A high index of suspicion is required for the diagnosis of this syndrome. Tight glycemic control, preferably by basal-bolus insulin regimen, usually leads to improvement in hepatomegaly and dyslipidemia, and majority of the metabolic consequences may be reversed, with improvement in growth and pubertal changes.
REFERENCES 1. Mahesh S, Karp RJ, Castells S, Quintos JB. Mauriac syndrome in a 3-year-old boy. Endocr Pract. 2007;13(1):63-6. 2. Kim MS, Quintos JB. Mauriac syndrome: growth failure and type 1 diabetes mellitus. Pediatr Endocrinol Rev. 2008;5 Suppl 4:989-93. 3. Patidar PP, Philip R, Saran S, Gupta KK. A rare case of Mauriac syndrome. Indian J Endocrinol Metab. 2012;16(3):486-7. 4. Mauriac P. Big belly, hepatomegaly, growth disorders in children with diabetes traits several years since insulin. Gaz Hebd Med Bordeau.1930;26:402-10. 5. Jackson RL, Holland E, Chatman ID, Guthrie D, Hewett JE. Growth and maturation of children with insulin-dependent diabetes mellitus. Diabetes Care. 1978;1(2):96-107. 6. Hamne B. Growth in a series of diabetic children on identical treatment with “free” diet and insulin 1944-1960. A contribution to the aetiology of diabetic dwarfism. Acta Paediatr Suppl.1962;135:72-82. 7. Lee RG, Bode HH. Stunted growth and hepatomegaly in diabetes mellitus. J Pediatr. 1977;91(1):82-4. 8. Ferry Robert J Jr, (Ed.). In: Management of Pediatric Obesity and Diabetes. New York City: Humana Press; 2011. pp. 383-5. 9. Torbenson M, Chen YY, Brunt E, Cummings OW, Gottfried M, Jakate S, et al. Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus. Am J Surg Pathol. 2006;30(4):508-13.
10. Pigui A, Montembault S, Bonte E, Hardin JM, Ink O. Voluminous hepatomegaly in a young diabetic patient. Gastroenterol Clin Biol. 2003;27(11):1038-40. ■■■■
Serum Iron and Ferritin Levels Associated with Microvascular Complications in Type 2 Diabetes Raised iron and serum ferritin levels have a significant positive association with HbA1c levels in patients with poorly controlled type 2 diabetes, says a new study presented at the American Association of Clinical Endocrinologists (AACE) annual meeting in Austin, Texas. These associations were also observed for microvascular complications of type 2 diabetes, including nephropathy, retinopathy and neuropathy.
Adrenalectomy Effective for Young Female Patients with Unilateral Primary Aldosteronism Adrenalectomy can be effective treatment for unilateral primary aldosteronism, particularly in younger and female patients, suggests the Primary Aldosteronism Surgical Outcome (PASO) study reported online May 30, 2017 in The Lancet Diabetes and Endocrinology. Fewer antihypertensive medications and absence of left ventricular hypertrophy were other factors independently associated with complete clinical success. Researchers recommend evaluation of outcomes in the first 3 months post-surgery, again at 6-12 months and then annually.
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Hearing Levels During Various Phases of Menstrual Cycle JYOTI YADAV
ABSTRACT The hearing levels are affected by several factors. Air and bone conduction was tested at frequency 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz in both the ears during different phases of menstrual cycle and the mean of all the four frequencies were calculated. In air conduction, there was highly significant difference between proliferative and menstrual phase (p < 0.001), significant difference between proliferative and luteal phase (p < 0.01) and insignificant difference between luteal and menstrual phase. In bone conduction, there was significant difference between proliferative and luteal phase (p < 0.05) and insignificant difference between proliferative and menstrual phase as well as between luteal and menstrual phase.
Keywords: Hearing levels, menstrual cycle, proliferative phase, luteal phase, menstrual phase, air conduction, bone conduction
M
enstrual cycle is divided into three phases. The follicular phase starts with menstrual bleeding and lasts on average for 15 days. The ovulatory phase lasts about 3 days, culminating in ovulation, when an ovule is released. The luteal phase lasts about 13 days and ends with the beginning of menstruation, which begins a new cycle. In the ovulatory phase, soon after ovulation, progesterone levels increase and luteinizing hormone (LH)/folliclestimulating hormone (FSH) and estrogen levels decrease. Progesterone levels peak is in luteal phase as LH/FSH levels decrease still further. High progesterone levels may increase sodium, chloride and water reabsorption. The cycle ends when progesterone and LH/FSH levels are at minimum, after which a new cycle begins.1
Hormone level variation in short time frame alter the whole female organism, leading to physical and emotional manifestations that may be quite evident. Homeostasis and the biochemical status of inner ear
Senior Professor and Head Dept. of Physiology Pt BD Sharma, PGIMS, Rohtak, Haryana Address for correspondence Dr Jyoti Yadav Senior Professor and Head Dept. of Physiology Pt BD Sharma, PGIMS, Rohtak, Haryana E-mail: drjyotiyadav2008@yahoo.com
fluid is essential for balance and for hearing. Changes in sodium and water reabsorption that take place during the menstrual cycle may affect the function of this part of the peripheral auditory system and may affect homeostasis, which causes auditory and labyrinthine symptoms.2 Various studies have tested the hypothesis that estrogen concentration variations in women changes the functional asymmetry.3-5 METHOD Study was performed in 20 female undergraduate medical students of age 18-20 years. They all were having regular menstrual cycles of 27-30 days and were not taking any medication or hormonal pills for the last 6 months. All of them were within the range of ideal body weight. None of the female had been taking hormonal contraceptive or other drug treatment that could alter their auditory function (such as cisplatin, aminoglycoside, hemodialysis). They had no history of endocrine pathology, hypertension or otological conditions. There was no ear disease and all had hearing threshold of 0-20 dB or better at octave interval frequencies from 500 to 4000 Hz. The hearing was tested by pure tone audiometry during 1st to 4th day (menstrual phase), 11th to 12th day (proliferative phase) and 21st to 22nd day (luteal phase). Air and bone conduction audiometry in both the ears were recorded by pure tone audiometry machine of RMS Medicare in a silent
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ENT room. Statistical analysis was done by analysis of variance (ANOVA) test. OBSERVATIONS Air and bone conduction tested at frequency 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz in both the ears during different phases of menstrual cycle. The mean of all the four frequencies of both the ears was calculated.
Air Conduction Air conduction was tested in various phases of menstrual cycle as shown in Table 1. There was highly significant difference between proliferative and menstrual phase (p < 0.001), significant difference between proliferative and luteal phase (p < 0.01) and nonsignificant difference between luteal and menstrual phase.
Bone Conduction Bone conduction was tested in various phases of menstrual cycle as shown in Table 2. There was significant difference between proliferative and luteal phase (p < 0.05). There was insignificant difference between proliferative and menstrual phase as well as between luteal and menstrual phase. DISCUSSION Clinical observations of Sator et al and Caruso et al strongly suggest that premenopausal and postmenopausal changes in gonadal function modify auditory thresholds.6,7 The influence of estrogen and other gonadal steroid substances may have direct
effects upon cochlea and various central auditory system pathways; they could indirectly influence central processing through other pathways and could also modulate blood flow in cochlea and brain.8 Oghan et al also found high frequency (4000-8000 Hz) hearing loss in patients of polycystic ovarian syndrome, which was attributed to hyperandrogenism seen in this syndrome.9 Caruso et al assessed auditory brainstem response in premenopausal women who were taking oral contraceptives. They observed that the wave latencies and interpeak intervals had shorter values during the periovular phase with respect to luteal phase (p < 0.05), the follicular phase for wave I and for interpeak interval I-V (p < 0.05) of the menstrual cycle. All of auditory brainstem response results in pill users were statistically different from those of the periovular phase (p < 0.05), though similar to those of both the luteal and follicular phases (p = NS). Thus, they concluded that auditory brainstem response depends on variations of ovarian steroids during menstrual cycle and during oral contraceptive intake.10 In air conduction, highly significant (p < 0.001) difference between proliferative and menstrual phase was observed and there was significant (p < 0.01) difference between proliferative and luteal phase. While the difference between luteal and menstrual phase was not significant as shown in Table 1. In bone conduction, the difference between proliferative and luteal phase was found just significant (p < 0.05), but the differences between proliferative and menstrual phase were found insignificant as shown in Table 2. Kadkhodaeian et al did not find any significant auditory perception changes by pure tone and speech reception
Table 1. Air Conduction Values of Both Ears Menstrual phase (dB) (1st-4th day) Mean ± SD 19.66 ± 3.672 SE
1.298
Proliferative phase (dB) (11th-12th day)
Luteal phase (dB) Proliferative vs. Proliferative vs. Luteal vs. luteal phase menstrual (21st-22nd day) menstrual phase (p value) (p value) phase (p value)
15.67 ± 5.449
18.95 ± 3.824
1.926
1.352
<0.001
<0.01
NS
SD = Standard deviation; SE = Standard error; NS = Nonsignificant.
Table 2. Bone Conduction Values of Both Ears
Mean ± SD SE
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Menstrual phase (dB) (1st-4th day)
Proliferative phase (dB) (11th-12th day)
Luteal phase (dB) (21st-22nd day)
Proliferative vs. menstrual phase (p value)
5.719 ± 6.030
-0.3125 ± 9.252
15.63 ± 27.57
NS
2.132
3.271
9.749
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Proliferative vs. Luteal vs. luteal phase menstrual phase (p value) (p value) <0.05
NS
ENT threshold audiometry.11 The use of oral contraceptives can provoke functional alterations in the inner ear, specially tinnitus and irritative peripheral vestibular syndrome in the risk group but auditory threshold alterations were not evident.12 Torres Larrosa et al found statistically significant differences in frequencies 9000, 10000 and 11200 Hz when mean of pre- and postmenstrual threshold values were compared.13 Petiot et al observed hearing performance at 4000 and 6000 Hz, and concluded that parametric analysis of results does not allow to reject the null hypothesis according to which the preovulatory and menstrual phases would not differ for auditory performance, when observed for resting thresholds, temporary threshold shifts and recovery processes of auditory fatigue.14 CONCLUSION Hearing levels are influenced by phases of menstrual cycle, which may be due to the variations in levels of hormones occurring during menstrual cycle phases. REFERENCES 1. Guyton AC. Sexual functions in the female and the female hormones. In: Textbook of Medical Physiology. Philadelphia: Saunders; 1976. pp. 1086-103. 2. Bittar RSM, Sanchez TG, Almeida ER, Bensadon RL. EstudodaFunçãoAuditiva Durante a Gestação Normal. Arquivos da FundoçãoOtorinolaringologia São Paulo, 1997Disponivelem:http://www.arquivosderol.org.br/ contendo/acervoport.asp?id=12. 3. Rode C, Wagner M, Güntürkün O. Menstrual cycle affects functional cerebral asymmetries. Neuropsychologia. 1995;33(7):855-65.
asymmetry across the menstrual cycle that are phase and task dependent. Neuropsychologia. 1998;36(9):869-74. 5. Alexander GM, Altemus M, Peterson BS, Wexler BE. Replication of a premenstrual decrease in right-ear advantage on language-related dichotic listening tests of cerebral laterality. Neuropsychologia. 2002;40(8):1293-9. 6. Sator MO, Franz P, Egarter C, Gruber DM, Wölfl G, Nagele F. Effects of tibolone on auditory brainstem responses in postmenopausal women - a randomized, double-blind, placebo-controlled trial. Fertil Steril. 1999;72(5):885-8. 7. Caruso S, Cianci A, Grasso D, Agnello C, Galvani F, Maiolino L, et al. Auditory brainstem response in postmenopausal women treated with hormone replacement therapy: a pilot study. Menopause. 2000;7(3):178-83. 8. Coleman JR, Campbell D, Cooper WA, Welsh MG, Moyer J. Auditory brainstem responses after ovariectomy and estrogen replacement in rat. Hear Res. 1994;80(2):209-15. 9. Oghan F, Coksuer H. Does hyperandrogenism have an effect on hearing loss in patients with polycystic ovary syndrome? Auris Nasus Larynx. 2012;39(4):365-8. 10. Caruso S, Maiolino L, Rugolo S, Intelisano G, Farina M, Cocuzza S, et al. Auditory brainstem response in premenopausal women taking oral contraceptives. Hum Reprod. 2003;18(1):85-9. 11. Kadkhodaeian S, Naghibzadeh M, Bakhshaei M. Auditory acuity throughout the menstrual cycle. Iranian J Otorhinolaryngol. 2005;16:4(38):11-4. 12. Mitre EI, Figueira AS, Rocha AB, Alves SM. Audiometric and vestibular evaluation in women using the hormonal contraceptive method. Braz J Otorhinolaryngol. 2006;72(3):350-4. 13. Torres Larrosa T, Pérez L, Guerrero M, Redondo F, López Aguado D. High-frequency audiometry: variations in auditory thresholds in the premenstrual period. Acta Otorrinolaringol Esp. 1999;50(8):603-6.
14. Petiot JC, Parrot J. Functional audiometry in women 4. Sanders G, Wenmoth D. Verbal and music dichotic during the preovulatory and menstrual phases. C R listening tasks reveal variations in functional cerebral Seances Soc Biol Fil. 1982;176(2):184-9. ■■■■
Strep Throat Linked to Risk of Mental Disorders in Children A study from Denmark has found an 18% increased risk of any mental disorder in children with a streptococcal throat infection. The risk of obsessive-compulsive disorder was 51% and that of tic disorders was 35%. The study is published online May 24, 2017 in JAMA Psychiatry.
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Congenital Cause of Status Epilepticus in an Adult: Tuberous Sclerosis Complex MOHAMED ILIYAS*, SUNDARAMURTHY†
ABSTRACT Tuberous sclerosis complex (TSC) is a rare neurocutaneous multisystemic genetic disorder. It is characterized by multiple hamartomas involving various organs, which are usually benign. Patients present with symptoms depending upon the organ involved. A thorough knowledge about the disease is required to diagnose the lesions in various organs. Some of them may be life-threatening and hence regular follow-up is required. We present the case of a young male who was brought with status epilepticus and was further evaluated and diagnosed as TSC in our hospital.
Keywords: Tuberous sclerosis complex, Bourneville’s disease, adenoma sebaceum, ash-leaf macules, shagreen patch, angiomyolipoma, cortical tubers, subependymal nodules, subependymal giant cell astrocytoma, confetti lesions, lymphangiomyomatosis
T
uberous sclerosis complex (TSC) is inherited in an autosomal dominant pattern with variable penetrance. Mutations in one of the two genes TSC1 (encoding hamartin) or TSC2 (encoding tuberin) are responsible for the manifestation of TSC. The genes for TSC1 and TSC2 are located at chromosome 9q34.3 and 16p13.3, respectively. The genetic products of both TSC1 and TSC2 form a single functional unit that is an upstream modulator in the mammalian target of rapamycin (mTOR) signaling pathway. Both these gene products downregulate the small G-protein Ras-homolog enriched in the brain (RHEB) activity in this pathway. Also called as Bourneville’s disease or Bourneville-Pringle disease, the name tuberous sclerosis complex is preferred now. Central nervous system is the most common affected organ with variable involvement of skin, kidney, heart, lung, eye, bone and teeth.
*Assistant Professor Dept. of Internal Medicine Shri Sathya Sai Medical College and Research Institute, Chennai, Tamil Nadu *Former Junior Resident †Professor Institute of Internal Medicine Rajiv Gandhi Government General Hospital and Madras Medical College Chennai, Tamil Nadu Address for correspondence Dr Mohamed Iliyas 1234, Madurapuri, Thuraiyur - 621 010, Tamil Nadu Email: dr.mohd.iliyas@gmail.com
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CASE REPORT A 24-year-old male was brought to our emergency department with a history of 4 episodes of generalized tonic-clonic seizures over 45 minutes without regaining consciousness in between the episodes. He was managed with anticonvulsants after securing his airway. His vitals were stabilized. The history of seizures dated back since childhood for which he was on irregular medications including native treatment. He had poor scholastic performance while his motor milestones were normal. On general examination, he had multiple facial angiofibromas over the nose in a butterfly distribution, forehead plaque, multiple hypomelanotic macules on his thighs, confetti lesions on his lower back (Figs. 1-3). There were no shagreen patch, periungual fibromas or café au lait spots. Tongue bite mark was present. His cardiovascular, respiratory, gastrointestinal and genitourinary systems were normal on clinical examination. His central nervous system was examined elaborately after he regained consciousness. He had a mini-mental state examination (MMSE) score of 23 and an IQ of 68. Motor, sensory, autonomic, cranial nerve and cerebellar examination were within normal limits. He had a pulse rate of 88/min, blood pressure (BP) - 128/86 mmHg, SpO2 - 99% with nasal oxygen, temperature of 98.60F and a respiratory rate of 18/min. His routine blood investigations including serum electrolytes were normal. Computed tomography (CT)
INTERNAL MEDICINE brain was done and it showed multiple subependymal calcified hamartomas in the walls of both lateral ventricles (Fig. 4). Three Tesla magnetic resonance imaging (MRI) of brain showed multiple cortical tubers in the right parietal and bilateral occipital lobes on T2 FLAIR sequences in coronal sections (Fig. 5). A 1.2 cm variable contrast enhancing lesion in the region of foramen of Monro suggestive of subependymal giant cell astrocytoma was found (Fig. 6).
Figure 1. Facial angiofibroma (adenoma sebaceum) - Multiple red brown fleshy papules over the nose and nasolabial fold in a butterfly distribution (black arrow). Forehead plaque - Raised well circumscribed skin-colored lesion of size 1 × 2 cm (white arrow).
Further investigations were done to look for the involvement of other internal organs. Contrastenhanced CT (CECT) of the abdomen showed evidence of well-defined heterodense lesions in the right kidney measuring 2.2 × 2.4 cm in the upper pole and 3.2 × 3.5 cm in the mid-pole with fat components and scattered enhancing areas post-contrast (Fig. 7). These lesions were characteristic of angiomyolipomas in the right kidney. Echocardiography was normal and there was no evidence of rhabdomyoma of the heart. No lymphangiomyomatosis of the lung or retinal hamartomas were found. There were no bone cysts. Based on the revised diagnostic criteria by Roach et al, our patient had 2 major criteria essential to make the diagnosis of TSC. He was started on regular anticonvulsants. Laser treatment was given for his facial angiofibroma for cosmetic reasons. He was advised for yearly screening of the angiomyolipoma, since risk
Figure 2. Hypomelanotic macule (ash-leaf spot) in the thigh of size 2.5 × 1 cm.
Figure 3. Confetti lesion. Scattered grain like hypomelanotic macules clustered in the lower back.
Figure 4. CT brain. Multiple subependymal calcified hamartomas in the walls of both lateral ventricles.
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INTERNAL MEDICINE of spontaneous rupture is high in lesions >4 cm. He was advised surgery for the subependymal giant cell astrocytoma. After his symptoms improved, he was discharged from the hospital.
Figure 7. CECT of abdomen. Well-defined heterodense lesions in the right kidney measuring 2.2 × 2.4 cm in the upper pole and 3.2 × 3.5 cm in the mid-pole with fat components and scattered enhancing areas post-contrast (arrows).
DISCUSSION
Figure 5. MRI brain - T2 FLAIR coronal section. Multiple wedge-shaped cortical tubers in the right parietal and bilateral occipital lobes (arrows).
Though TSC was described in a stillborn by von Recklinghausen in 1863, Bourneville gave the disease its present name in 1880.1 It has a prevalence of less than 1:5,000 births. In the present day, the diagnosis is based on the Updated Diagnostic Criteria for TSC in 20122 (Table 1). Either a genetic or clinical diagnostic criteria is used, with 2 major or 1 major and 2 minor features required for a definite diagnosis. For a possible diagnosis either 1 major or ≥2 minor features are needed. Genotypephenotype studies reveal that individuals with TSC2 mutation tend to have more severe disease. The lesions of TSC can be seen from fetal life to adulthood (Table 1). Neurological manifestations include seizures, cognitive disability and behavioral abnormalities such as autism, which occurs equally in both the genders. All types of seizures have been reported, often refractory to treatment, even to polytherapy with antiepileptic drugs.3 Cortical tubers extend in a wedge-shaped manner from the ventricular wall to the cortex. Clinical studies have suggested that higher number of tubers (>7) is associated with the development of infantile spasms and intractable epilepsy but they don’t correlate with the number of subependymal nodules. Vigabatrin is more effective in controlling infantile spasms than adrenocorticotrophic hormone.
Figure 6. MRI brain with contrast revealed a 1.2 cm variable contrast enhancing lesion in the region of foramen of Monro suggestive of subependymal giant cell astrocytoma.
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Seizure originating from single cortical tubers respond to resective epileptic surgery. Subependymal nodules are usually found near the foramen of Monro, enlarging
INTERNAL MEDICINE Table 1. Updated Diagnostic Criteria for TSC 2012 Genetic Diagnostic Criteria The identification of a pathogenic mutation in either TSC1 or TSC2 Is sufficient to make a definite diagnosis of TSC Clinical Diagnostic Criteria Major features
Age at onset
1. Hypomelanotic macules (≥3, at least 5 mm diameter)
Infancy to adulthood
2. Angiofibromas (≥3) or fibrous cephalic plaque
Infancy to adulthood
3. Ungual fibromas (≥2)
Adolescence to adulthood
4. Shagreen patch
Childhood
5. Multiple retinal hamartomas
Infancy
6. Cortical dysplasias
Fetal life
7. Subependymal nodules
Childhood to adolescence
8. Subependymal giant cell astrocytoma
Childhood to adolescence
9. Cardiac rhabdomyoma
Fetal life
10. Lymphangiomyomatosis
Adolescence to adulthood
11. Angiomyolipomas
(≥2) Childhood to adulthood
Minor features 1. Confetti skin lesions 2. Dental enamel pits (≥3) 3. Intraoral fibromas (≥2) 4. Retinal achromic patch 5. Multiple renal cysts 6. Nonrenal hamartomas Definite diagnosis: 2 major features or 1 major and ≥2 minor features. Possible diagnosis: Either 1 major feature or ≥2 minor features.
over time to form subependymal giant cell astrocytomas (SEGAs) to cause obstructive hydrocephalus. SEGAs are benign and cured by early surgery. Their growth is inhibited by rapamycin and everolimus.4 Renal angiomyolipomas are benign tumors composed of vascular tissue, smooth muscle and fat, majority of which are multiple and bilateral. Surgical resection is indicated for lesions more than 3-4 cm size because of the high incidence of aneurysm and hemorrhage. Embolization can be tried to prevent rupture. Similar to the effect on SEGAs, rapamycin and everolimus can limit their growth. Yearly radiological screening is advised to monitor their growth. Renal cysts are common. Multiple cardiac rhabdomyomas are present, frequently diagnosed by fetal ultrasonography. Symptoms of
cardiac failure, arrhythmia (Wolff-Parkinson-White syndrome, complete heart block, ventricular and atrial tachycardia) and cerebral thromboembolism respond to diuretics, digoxin and surgery.5 Annual or biannual screening is advised. Unlike other lesions of TSC, rhabdomyomas have the tendency to resolve spontaneously.6 Pulmonary lymphangiomyomatosis present with cough, hemoptysis, pneumothorax and dyspnea. Females have a higher incidence. The mortality rate is high, around 10% by 10 years. Tamoxifen, progesterone, rapamycin and everolimus are shown to be effective in treatment. Hypomelanotic macules (ash-leaf spots) are the most common skin lesions. A minimum of 3 lesions are required for diagnosis. Confetti lesions are stippled
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INTERNAL MEDICINE hypopigmented areas usually found in the extremities. Poliosis of hair, scalp and eyelids can be seen less frequently. Facial angiofibroma (adenoma sebaceum) are hamartomas that are multiple small pinkish, erythematous papules that tend to coalesce to form plaques. They usually appear on the central part of the face bilaterally and symmetrically, involving the nasolabial folds characteristically in a butterfly pattern. Multiple treatment options including cryotherapy, radiofrequency ablation, electrocoagulation, dermabrasion and laser therapy are available of which treatment with CO2 laser shows excellent cosmetic results.7 Oral and topical rapamycin for angiofibromas are widely studied. Forehead plaques or fibrous facial plaques are nonpopular lesions resembling angiofibromas. Ungual fibromas are seen adjacent and underneath the nail. Shagreen patch is a flesh-colored irregular raised lesion usually found in the lower back.
REFERENCES 1. Bourneville DM. Sclerose tubereuse des circonvolutions cerebrales: idiotie et epilepsie hemiplegique. Arch Neurol (Paris). 1880;1:81-91. 2. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998;13(12):624-8. 3. Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol. 2004;19(9):680-6. 4. Franz DN. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex. Biologics. 2013;7:211-21. 5. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355(13):1345-56. 6. Smythe JF, Dyck JD, Smallhorn JF, Freedom RM. Natural history of cardiac rhabdomyoma in infancy and childhood. Am J Cardiol. 1990;66(17):1247-9.
7. Salido-Vallejo R, Garnacho-Saucedo G, MorenoGiménez JC. Current options for the treatment of facial angiofibromas. Actas Dermosifiliogr. 2014;105(6):558-68. ■■■■
New ADA/AADE Guidelines for Diabetes Self-management Education and Support The American Diabetes Association (ADA) and the American Association of Diabetes Educators (AADE) released “2017 National Standards for Diabetes Self-management Education and Support” (Standards) online on July 28, 2017, to be published in the September 2017 issues of Diabetes Care and The Diabetes Educator. The Standards outline and define evidence-based, specific guidelines to help diabetes educators and medical providers establish and sustain patient care models, programs and teams for people with diabetes and their caregivers.
Oral Truvada and Vaginal Ring are Safe, Acceptable for HIV Prevention in Adolescents A monthly vaginal ring and a daily oral tablet as pre-exposure prophylaxis (PrEP), both containing anti-HIV drugs, were safe and acceptable in studies of adolescents, according to the results of Choices for Adolescent Prevention Methods for South Africa, or CHAMPS PlusPills and ASPIRE trial presented July 25, 2017 at the 9th IAS Conference on HIV Science in Paris.
Continuing Antibiotic Prophylaxis for Recurrent Cellulitis is Effective A new Cochrane Review published online June 20, 2017 in the Cochrane Database of Systematic Reviews has reported that compared with no treatment or placebo, taking antibiotics decreased the risk of future episodes by 69%, reduced their number by more than 50% and prolonging the time to recurrence with recurrent cellulitis of the lower limbs suggesting that antibiotic prophylaxis for recurrent cellulitis is effective, until the antibiotics are stopped.
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Anti-PL-12: Antisynthetase Syndrome TUHINA PARVEEN SARWALA*, MANISH N MEHTA†, AJAY C TANNA‡, JEMIMA BHASKAR#, RAJESH SADIYA¥
ABSTRACT Antisynthetase syndrome (ASS) is a rare idiopathic inflammatory myopathy and chronic autoimmune systemic disease. The hallmark is presence of antisynthetase antibodies among which anti-Jo-1 is the commonest. Being a rare syndrome, its presence in general population is unknown. Females have a twofold higher prevalence than males. Here, we report the case of a 51-yearold lady having interstitial lung disease as the only manifestation of ASS with raised anti-PL-12 antibody levels.
Keywords: Antisynthetase syndrome, interstitial lung disease, Jo-1, PL-12, inflammatory, myopathy
A
ntisynthetase syndrome (ASS) is characterized by systemic involvement of the muscles (myositis), lungs (interstitial lung disease or ILD), joints (polyarthritis), mechanic’s hands and Raynaud’s phenomena besides fever. Nine antisynthetase antibodies have been described till date. They include Jo-1, PL-7, PL-12, OJ, EJ, KS, Wa, Zo and YRS. Anti-Jo-1 antibodies are the commonest. This patient presented with PL-12 antibodies.
CASE REPORT A 51-year-old lady presented with complaints of cold, cough with whitish expectoration and breathlessness on exertion since 1 month. She did not have fever, chest pain, pedal edema, orthopnea, paroxysmal nocturnal dyspnea. There was no joint pain or muscle ache. She had similar complaints since 8 years and was diagnosed to have ILD, for which she had been on steroids on and off. During this episode, examination of respiratory system revealed mild dyspnea and bilateral
*Senior Resident †Professor and HOD ‡Assistant Professor #Senior Resident ¥2nd Year Resident Dept. of Internal Medicine MP Shah Medical College and Guru Gobind Singh Hospital, Jamnagar, Gujarat Address for correspondence Dr Jemima Bhaskar 404, Kings Palace, Opposite Mehulnagar, Opposite BSNL Telephone Exchange, Jamnagar, Gujarat E-mail: jemimabhaskar@yahoo.com
crepitations. Her hemoglobin level was 9.4 g/dL with microcytic hypochromic anemia, serum creatinine 1.2 mg/dL, chest X-ray showed interstitial pneumonia and computed tomography (CT) thorax showed ground glass imaging in periphery. Ultrasonography (USG) abdomen and 2D echo was normal. Eight years ago, antinuclear antibody (ANA) profile was negative and Jo-1 was positive. This time ANA profile was negative but raised PL-12 antibody levels were found. Spirometry showed restrictive pattern of lung disease. DISCUSSION Antisynthetase syndrome is a systemic disease. Its main clinical features are fever, myositis, polyarthritis, ILD, mechanic’s hands and Raynaud’s phenomena. Fever presents in about 20% of patients. It may occur at the onset of disease or may persist or recur with relapses. Myositis is present in more than 90% of patients. It is associated with anti-Jo-1 antibodies, 50% of patients experience joint pain or inflammatory arthritis (Table 1). In most of them, symmetrical arthritis of small joints of hands and feet are seen. Typically, it does not result in bony erosions. Suggested classification for inflammatory myopathies is summarized in Table 2. ILD develops in association with anti-Jo-1 antibodies. It often presents with sudden or gradual onset of deterioration of breath on exertion. Sometimes, it causes intractable dry cough. It may lead to pulmonary hypertension. Mechanic’s hands affect about 30% of the patients. Thickened skin of tips and margins of fingers resemble a mechanic’s hands. Reynaud’s phenomena occurs in 40% of the patients. It is due to an episodic
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INTERNAL MEDICINE Table 1. Antinuclear Antibodies in Inflammatory Muscle Diseases* Antibody specificity Prevalence (%) Anti-tRNA synthetases Histidyl (Jo-1) Threonyl (PL-7) Alanyl (PL-12) Glycyl (EJ) Isoleucyl (OJ) Asparaginyl (KS) Selenacysteinyl (Mas) Mi-2 Signal recognition particle KJ Protease Histone RNPs U1 U2 Ro La PM-Sci Elongation factor 1α (Fer) Histone Ku U3 snoRNP CADM-140 MDA5 p140 p155 SUMO-1 TIF-γ
20-30 1-5 1-5 1-5 1-5 ? 1-2 8 (15-20% of DM) 4 <1 62 17 12 3 10 ? 8 1 ? ? ? ? ? ? ? ? ?
Disease specificity Myositis Myositis Myositis Myositis Myositis Overlap Myositis† Myositis‡ No Myositis‡ No No No
Major disease associations Antisynthetase syndrome
? Dermatologic involvement
MCTD features
Overlap No No Overlap Overlap
Overlap
Amyopathic DM Amyopathic DM DM DM and cancer - associated DM DM DM and cancer - associated DM
*Shown are major antinuclear antibody specificities described in inflammatory myositis, along with estimated prevalences and disease associations (bold indicates data supported by multiple studies). †Considered ‡Often
a myositis-specific autoantibody (MSA) despite recent findings in autoimmune hepatitis.
referred to as MSAs.
DM = Dermatomyositis; MDAS = Melanoma differentiation-associated gene 5; RNP = Ribonucleoprotein; snoRNP = Small nucleolar RNP; snRNP = Small nuclear RNP; SUMO-I = Small ubiquitin-like modifier activating enzyme subunits A and B; TIFI-γ = Transcriptional intermediary factor 1-γ, tRNA = Transfer RNA.
reduction in blood supply of the fingers and toes which turn white, then blue and finally red. Cold and emotional stress triggers it. In some patients, nail bed capillary malformations are seen. Some case studies have reported malignancies occurring within 6-12 months after diagnosis of ASS. Clinical presentation presents a clue to the diagnosis. Investigations may include muscle enzymes, muscle antibodies, electromyography (EMG), magnetic resonance imaging (MRI) of affected muscles and biopsy, lung function tests, high resolution CT scan of thorax, lung biopsy. Presence of serum antibodies directed against amino acid t-RNA synthetases is the definitive diagnosis. These are cellular enzymes involved in protein synthesis. Glucocorticoids are the
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main treatment of ASS. Prognosis is generally grave. The autoantibodies may be antinuclear or cytoplasmic. Systemic lupus erythematosus (SLE) is usually diagnosed by the presence of ANAs (Table 3). Cytoplasmic antibodies against amino acid t-RNA synthetases are a different class by themselves. They are Jo-1, PL-7, PL-12, OJ, EJ, KS, Wa, Zo and YRS. ASS presents with one of these antibodies exclusively. ANAs are absent. The correlations of autoantibodies with clinical features is presented in Table 4. This patient had ILD as the initial and the only presentation with no evidence of myositis or arthritis. This is a rarity. In addition, in spite of recurrence of symptoms, her condition has not deteriorated for the past 8 years. Also, she has detectable PL-12 antibody
INTERNAL MEDICINE Table 2. Suggested Classification for Inflammatory Myopathies Abbreviation
Description
PM
Pure polymyositis
DM
Pure dermatomyositis
OM
Overlap myositis: myositis with at least 1 clinical overlap feature and/or an overlap autoantibody
CAM
Cancer-associated myositis: with clinical paraneoplastic features and without an overlap autoantibody or anti-Mi-2
Bohan and Peter's definition of myositis
1. Symmetric proximal muscle weakness. 2. Elevation of serum skeletal muscle enzymes. 3. Electromyographic triad of short, small, polyphasic motor unit potentials; fibrillations, positive sharp waves and insertional irritability and bizarre, high-frequency repetitive discharges.
4. Muscle biopsy abnormalities of degeneration, regeneration, necrosis, phagocytosis and an interstitial mononuclear infiltrate. 5. Typical skin rash of DM including the heliotrope rash, Gottron sign and Gottron papules. Definite myositis: 4 criteria (without the rash) for PM, 3 or 4 criteria (plus the rash) for DM. Probable myositis: 3 criteria (without the rash) for PM, 2 criteria (plus the rash) for DM. Possible myositis: 2 criteria (without the rash) for PM, 1 criterion (plus the rash) for DM. Definition of clinical overlap features Inflammatory myopathy plus at least 1 or more of the following clinical findings: polyarthritis, Raynaud's phenomenon, sclerodactyly, scleroderma proximal to metacarpophalangeal joints, typical SSc-type calcinosis in the fingers, lower esophageal or small-bowel hypomotility, DLCO lower than 70% of the normal predicted value, interstitial lung disease on chest radiogram or computed tomography scan, discoid lupus, anti-native DNA antibodies plus hypocomplementemia, 4 or more of 11 American College of Rheumatology criteria for systemic lupus erythematosus, antiphospholipid syndrome. Definition of overlap autoantibodies Antisynthetases (Jo-1, PL-7, PL-12, OJ, EJ, KS); scleroderma-associated autoantibodies (scleroderma-specific antibodies: centromeres, topoisomerase I, RNA polymerases I or III, Th; and antibodies associated with scleroderma overlap: Ul-RNP, U2-RNP, U3-RNP, U5-RNP, Pm-Scl, Ku, and other autoantibodies (signal recognition particle, nucleoporins). Definition of clinical paraneoplastic features Cancer within 3 year of myositis diagnosis, plus absence of multiple clinical overlap features; plus, if cancer was cured, myositis was cured as well.
Table 3. Antinuclear Antibodies in Systemic Lupus Erythematosus* Antibody specificity
Prevalence (%)
SLE specific?
Major disease associations
Chromatin
80-90
In high titer
dsDNA
70-80
In high titer
Renal LE, overall disease activity
Histone
50-70
No
Drug-induced lupus, anti-DNA Overlap
Chromatin-associated antigens
H1, H2B > H2A > H3 > H4 Ku
20-40
No
RNA polymerase II
9-14
Relatively (SLE and overlap)
6
No
3-6
No
Sm core
20-30
Yes No
Kinetochore PCNA Ribonucleoprotein components snRNPs U1 snRNP
30-40
U2 snRNP
15
U5 snRNP
?
U7 snRNP
? Cont'd...
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INTERNAL MEDICINE ...Cont'd
Table 3. Antinuclear Antibodies in Systemic Lupus Erythematosus* Prevalence (%)
SLE specific?
Major disease associations
Ro/SS-A
Antibody specificity
40
No
Cutaneous LE
La/SS-B
10-15
No
Neonatal LE
10-20
Yes
Neuropsychiatric LE
Neonatal LE and CHB Ribosomes PO, P1, P2 protein 28S rRNA
?
S10 protein
?
L5 protein
?
L12 protein
?
SR proteins
50-52
Proteasome
58
TNF TRs
61
RNA helicase A
6
RNA
?
Ki-67
?
Nephritis
*Shown are major antinuclear antibody specificities described in SLE, along with estimated prevalences and disease associations (bold indicates data supported by multiple studies). CHB = Congenital heart block; dsDNA = Double-stranded DNA; LE = Lupus erythematosus; PCNA = Proliferating cell nuclear antigen; rRNA = Ribosomal RNA; SLE = Systemic lupus erythematosus; snRNP = Small nuclear ribonucleoprotein; TNF TRs = TNF translational regulators, including T-cell intracytoplasmic antigen 1 (flA-1) and TIA-1-related protein (TIAR).
Table 4. Correlations of Autoantibodies with Clinical Features Autoantigen Clinical associations Rheumatoid factor RA, erosive arthritis, cryoglobulinemia Anticyclic citrullinated protein RA Nucleosome SLE, Sci, MCTD Proteasome SLE, PM/DM, Sjogren's syndrome, multiple sclerosis Sm snRNP SLE Histones H1, H2A, H2B, H3, H4 SLE, UCTD, RA, PBC, generalized morphea Ribosomal P SLE psychosis dsDNA SLE, glomerulonephritis, vasculitis ACL/β-glycoprotein SLE, thrombosis, thrombocytopenia, miscarriages MCTD (not associated with APL syndrome) β2-glycoprotein-independent ACL 68-kD peptide of U1-RNP MCTD, Raynaud's, pulmonary hypertension U1 snRNP MCTD, SLE, PM hnRNP-A2 (also called RA-33) MCTD, RA, erosive arthritis in SLE and Scl Ro/La Sjogren's, SLE, congenital heart block, photosensitivity, PBC Fodrin Sjogren's, glaucoma, moyamoya disease Platelet-derived growth factor Diffuse and limited Scl Topoisomerase I (Scl-70) Diffuse Scl with prominent organ involvement Centromere Limited Scl, CREST, Raynaud's, pulmonary hypertension, PBC Th/To Limited Scl U3-snRNP Limited Scl hnRNP-l Scl (early diffuse and limited) RNA polymerases I and III Scl (diffuse with renovascular hypertension) Fibrillarin Severe generalized Scl Ku Myositis overlap, primary pulmonary hypertension, Graves' disease U5-snRNP Myositis overlap PM/Scl Myositis overlap with arthritis, skin lesions, mechanic's hands Signal recognition particle Myositis overlap (severe course with cardiac disease) Antisynthetases (Jo-1, PL-7, PL-12) Myositis overlap with arthritis and interstitial lung disease Cont'd...
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INTERNAL MEDICINE ...Cont'd
Table 4. Correlations of Autoantibodies with Clinical Features Autoantigen Clinical associations Mi-2 Dermatomyositis Proteinase-3 Granulomatosis with polyangiitis (formerly Wegener's granulomatosis), pulmonary capillaritis Myeloperoxidase Churg-Straus, pauci-immune glomerulonephritis Endothelial cell Pulmonary hypertension, severe digital gangrene α-Enolase Behcet's, RA, MCTD, Scl, Takayasu’s Angiotensin-converting enzyme 2 AlCTDs with vasculopathy
ACL = Anticardiolipin; AlCTDs = Autoimmune connective tissue diseases; APL = Antiphospholipid syndrome; CREST = Syndrome of calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia; DM = Dermatomyositis, hn = Heterogeneous nuclear, MOD = Mixed connective tissue disease; PBC = Primary biliary cirrhosis; PM = Polymyositis; RA = Rheumatoid arthritis; RNP = Ribonucleoprotein particle; Scl = Scleroderma; SLE = Systemic lupus erythematosus; sn = Small nuclear; UCTD = Undifferentiated connective tissue disease.
levels which is rare, Jo-1 being the commonest in the community. CONCLUSION Presentation of ILD on imaging should raise clinical suspicion of ASS, more so if associated joint pain or muscle pain is there.In resource constrained settings, when patients with ILD and features suggesting connective tissue disorder (CTD) are evaluated, serum ANA levels are used as screening test. If it is negative, other autoantibodies are not worked for. As a result the diagnosis of ASS is missed and such patients are often
labeled as CTD. This patient was also misdiagnosed and treated as CTD for 8 years. PL-12 was positive only during the recent admission. Hence, the diagnosis of ASS was made. SUGGESTED READING 1. Kelly’s Textbook of Rheumatology. 9th Edition, Volume I, Chapter 55. 2. Kelly’s Textbook of Rheumatology. 9th Edition, Volume II, Chapter 85-86.
3. Fauci KN. Harrison’s Principles of Internal Medicine. 19th Edition, Volume 2, Chapter 378. ■■■■
FIT may be an Alternative Screening Method for Patients at High Risk for Colorectal Cancer A meta-analysis reported online June 19, 2017 in JAMA Internal Medicine has shown that fecal immunochemical testing (FIT) had high overall diagnostic accuracy for colorectal cancer and moderate accuracy for advanced neoplasia in high-risk patients. The average sensitivity of FIT for colorectal cancer was 93% (95% CI, 53-99%), and the average specificity was 91%, while for advanced neoplasia, the average sensitivity was 48% and the average specificity was 93%.
Yoga as Good as Physiotherapy for Chronic Low Back Pain In patients with mild-to-moderate chronic low back pain, yoga was found to be as good as physiotherapy in improving pain. These improvements were maintained at 1 year with no between-group differences. Adverse events were also comparable between the two groups. The study was published June 20, 2017 in the Annals of Internal Medicine.
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Every citizen of India should have the right to accessible, affordable, quality and safe heart care irrespective of his/her economical background
Sameer Malik Heart Care Foundation Fund An Initiative of Heart Care Foundation of India
E-219, Greater Kailash, Part I, New Delhi - 110048 E-mail: heartcarefoundationfund@gmail.com Helpline Number: +91 - 9958771177
“No one should die of heart disease just because he/she cannot afford it” About Sameer Malik Heart Care Foundation Fund
Who is Eligible?
“Sameer Malik Heart Care Foundation Fund” it is an initiative of the Heart Care Foundation of India created with an objective to cater to the heart care needs of people.
Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment. Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background. Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program. Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country. To promote heart care research in India.
All heart patients who need pacemakers, valve replacement, bypass surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. org and submitted in the HCFI Fund office.
Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License. The patient must be needy and underprivileged, to be assessed by Fund Committee. The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof. The review of applications may take 4-6 weeks. All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications. The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.
To promote and train hands-only CPR.
Activities of the Fund Financial Assistance
The HCFI Fund reserves the right to advise/direct the beneficiary to the designated hospital for the treatment.
Financial assistance is given to eligible non emergent heart patients. Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.
The financial assistance granted will be given directly to the treating hospital/medical center.
After the sanction of grant, the fund members facilitate the patient in getting his/her heart intervention done at state of art heart hospitals in Delhi NCR like Medanta – The Medicity, National Heart Institute, All India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant Hospital, Jaipur Golden Hospital, etc. The money is transferred directly to the concerned hospital where surgery is to be done.
Drug Subsidy
The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted). The HCFI Fund does not provide assistance for any emergent heart interventions.
Check List of Documents to be Submitted with Application Form Passport size photo of the patient and the family A copy of medical records Identity proof with proof of residence Income proof (preferably given by SDM)
The HCFI Fund has tied up with Helpline Pharmacy in Delhi to facilitate
BPL Card (If Card holder)
patients with medicines at highly discounted rates (up to 50%) post surgery.
Details of financial assistance taken/applied from other sources (Prime Minister’s Relief Fund, National Illness Assistance Fund Ministry of Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi Arogya Nidhi), etc., if anyone.
The HCFI Fund has also tied up for providing up to 50% discount on imaging (CT, MR, CT angiography, etc.)
Free Diagnostic Facility
Free Education and Employment Facility
The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi.
HCFI has tied up with a leading educational institution and an export house in Delhi NCR to adopt and to provide free education and employment opportunities to needy heart patients post surgery. Girls and women will be preferred.
This machine is used to screen children and adult patients for any heart disease.
Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests.
About Heart Care Foundation of India
Help Us to Save Lives The Foundation seeks support, donations and contributions from individuals, organizations and establishments both private and governmental in its endeavor to reduce the number of deaths due to heart disease in the country. All donations made towards the Heart Care Foundation Fund are exempted from tax under Section 80 G of the IT Act (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration (Reg. No 231650979). The objectives and activities of the trust are charitable within the meaning of 2 (15) of the IT Act 1961.
Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof. HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.
Objectives Preventive Health Care Education Perfect Health Mela Providing Financial Support for Heart Care Interventions Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops Research in Heart Care
Donate Now... Heart Care Foundation Blood Donation Camps The Heart Care Foundation organizes regular blood donation camps. The blood collected is used for patients undergoing heart surgeries in various institutions across Delhi.
Committee Members
Chief Patron
President
Raghu Kataria
Dr KK Aggarwal
Entrepreneur
Padma Shri, Dr BC Roy National & DST National Science Communication Awardee
Governing Council Members Sumi Malik Vivek Kumar Karna Chopra Dr Veena Aggarwal Veena Jaju Naina Aggarwal Nilesh Aggarwal H M Bangur
Advisors Mukul Rohtagi Ashok Chakradhar
Executive Council Members Deep Malik Geeta Anand Dr Uday Kakroo Harish Malik Aarti Upadhyay Raj Kumar Daga Shalin Kataria Anisha Kataria Vishnu Sureka
This Fund is dedicated to the memory of Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age.
Rishab Soni
HCFI has associated with Shree Cement Ltd. for newspaper and outdoor publicity campaign HCFI also provides Free ambulance services for adopted heart patients HCFI has also tied up with Manav Ashray to provide free/highly subsidized accommodation to heart patients & their families visiting Delhi for treatment.
http://heartcarefoundationfund.heartcarefoundation.org
INTERNAL MEDICINE
Ramsay Hunt Syndrome with Multidermatomal Zoster: A Case Report MOHAMED ILIYAS*, VISWANATHAN NEELAKANTAN†, UMA DEVI‡
ABSTRACT Primary infection with varicella-zoster virus causes varicella (chickenpox) and its reactivation from the sensory ganglion causes herpes zoster (shingles). Though herpes zoster usually occurs in a single dermatomal distribution, multidermatomal zoster and disseminated cutaneous zoster are common in immunocompromised individuals. It is very unusual for herpes zoster to present with simultaneous involvement of spinal and cranial nerve ganglions. We report one such case diagnosed in our hospital.
Keywords: Ramsay Hunt syndrome, herpes zoster oticus, diabetes mellitus, Bell’s phenomenon, varicella-zoster virus, multidermatomal zoster, disseminated cutaneous zoster, geniculate herpes
R
amsay Hunt syndrome (RHS) is characterized by the triad of ipsilateral facial paralysis, ear pain and vesicles in the auditory canal or auricle.1 It occurs due to the reactivation of latent varicellazoster virus in the geniculate ganglion, hence called as geniculate herpes or herpes zoster oticus. It is considered to be a cranial polyneuropathy with the involvement of multiple cranial nerves. Of the cranial nerves, facial and glossopharyngeal are most commonly involved, while 5, 8, 10, 11 and 12 are also affected.1 Of the spinal ganglions, thoracic (T5-T10) and lumbar dermatomes are most commonly involved.2
suffered from chickenpox in her childhood. She was not on any immunosuppressant drugs. Her vitals were blood pressure (BP) - 130/80 mmHg, pulse rate - 78/min, temperature - 98.60F, respiratory rate - 16/min. On examination, she had multiple vesicles with crusting in the ear lobule, occiput, neck, shoulder and angle of the
CASE REPORT A 45-year-old female came to medical outpatient department (OPD) with the symptoms of right-sided throbbing headache, right ear pain, watering from right eye, difficulty in closing the right eye, deviation of angle of mouth towards left side, while eating and speaking since 4 days (Fig. 1). There was no history of fever, trauma, seizure or loss of consciousness. There was no history of hearing loss or vertigo. She has
*Assistant Professor †Former Professor ‡Professor and HOD Dept. of Internal Medicine Shri Sathya Sai Medical College and Research Institute, Chennai, Tamil Nadu Address for correspondence Dr Mohamed Iliyas 1234, Madurapuri, Thuraiyur - 621 010, Tamil Nadu E-mail: dr.mohd.iliyas@gmail.com
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Figure 1. Right-sided facial palsy of lower motor neuron type on admission (Day 5). There is loss of nasolabial fold, deviation of angle of mouth to the left side and minimal eye closure with overflow of tears. Skin lesions are present in the neck.
INTERNAL MEDICINE mandible on the right side. The distribution of the skin lesions corresponded to C2, C3, C4 and C5 dermatomes (Fig. 2). Neurological evaluation revealed weakness of the facial muscles supplied by the right facial nerve. The weakness was of lower motor neuron type involving both upper and lower half of face. Bellâ&#x20AC;&#x2122;s phenomenon was demonstrable. There was loss of taste sensation to all modalities of taste over the anterior two-thirds of the right half of tongue. Only facial nerve was involved. Other cranial nerves were normal on examination. There was no sensory loss in the C2, C3, C4 and C5 dermatomal distribution. There was no weakness of muscles supplied by C2, C3, C4 and C5 nerve roots. Ear, nose and throat examination was normal. There were no vesicles on the tympanic membrane. There was no hearing loss.
Figure 2. Multidermatomal zoster. Healed vesicles with crusting over the ear lobule, angle of mandible, neck and shoulder corresponding to C2, C3, C4 and C5 dermatomes.
Routine blood investigation showed a high random blood sugar level of 356 mg/dL. Glycosylated hemoglobin (HbA1c) was 9.1%. Human immunodeficiency virus (HIV) screening with enzyme-linked immunosorbent assay (ELISA) was negative. Other investigations were within normal limits. She was treated with tablet prednisone at a dose 1 mg/kg/day, tablet acyclovir 800 mg 5 times daily, tablet pregabalin 75 mg once in the night along with insulin injections titrated to the capillary blood glucose. Regular physiotherapy was given for her facial muscles along with artificial tears for the eyes and protective strapping of the eyelids. There was partial recovery of the taste sensation on Day 5 and facial muscles on Day 7 of steroids (Fig. 3). Steroids were tapered and stopped on Day 10 along with acyclovir. Diabetes was managed with tablet metformin 500 mg thrice-daily. She was discharged with regular follow-up in medicine and physiotherapy OPD. DISCUSSION
Figure 3. Day 10. Partial recovery of facial weakness with healed skin lesions. Moderate eye closure.
Herpes zoster is caused by varicella-zoster virus, a DNA virus affecting the nervous system with an incidence of 3 to 5 cases per 1,000 persons/year. It manifests by painful vesicular eruptions limited to a single dermatome on one side. Multidermatomal zoster involves more than one dermatome unilaterally. Disseminated cutaneous zoster signifies bilateral cutaneous lesions. Chickenpox is usually highly contagious with a high household secondary attack rate of >90%. Zoster on the other hand is not contagious except in those who have not suffered from chickenpox. Chickenpox is usually common in winter and spring seasons, while zoster has no such seasonal predilection.
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INTERNAL MEDICINE Its incidence is equal on both sides of the body and between both the sexes. Zoster is common among immunocompromised individuals and elderly, affecting 10% of lymphoma and 25% of Hodgkin’s disease patients. Our patient had noninsulin-dependent diabetes mellitus, which was diagnosed after hospitalization. Zoster may be associated by segmental sensory loss and delayed motor loss in 5% of patients. Other than the spinal and cranial sensory ganglia, both the anterior and posterior spinal roots can be involved as well as posterior grey matter of spinal cord and the leptomeninges adjacent to it. Pain is the most common symptom of zoster. Presence of pain without a rash signifies, “zoster sine herpete”. The diagnosis of herpes zoster is straight forward in immunocompetent individuals with pain and rash limited to a dermatome. In immunocompromised individuals, there can be atypical presentation and the diagnosis is supported by laboratory investigations. Lipschutz inclusion bodies are seen in epidermal cells. These are homogenous eosinophilic, ovoid structures that produces perinuclear halo by displacing the nucleolus and chromatin. Polymerase chain reaction assays can be done in fluids from the vesicles, cerebrospinal fluid (CSF) and bronchoalveolar lavage. They have a high sensitivity compared to viral culture and high specificity.3 Direct fluorescent antibody (DFA) can give results within 90 minutes. The sample is collected from the skin scraping of vesicles that have not yet crusted. Simultaneous detection of varicellazoster and herpes simplex viruses can be done by DFA. Treatment is with acyclovir, famciclovir or valacyclovir. Post-herpetic neuralgia is the most common complication following zoster. Other complications include aseptic meningitis, encephalitis, myelitis, peripheral motor neuropathy, Guillain-Barre syndrome and stroke due to granulomatous vasculitis. RHS is a rare cause of facial nerve palsy with an incidence of 5 per 1,00,000 persons/year but the second common cause of nontraumatic facial palsy.1 The strict definition of the RHS is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth. Otalgia is the 2nd most common symptom next to facial paralysis. Our patient did not have otalgia and presented with facial paralysis. Since vestibulocochlear nerve is involved frequently in RHS because of its close proximity to geniculate ganglion in the bony facial canal, patients may have tinnitus, hearing loss, vertigo, nystagmus, nausea and vomiting. Our patient did not have these features. The facial nerve palsy in RHS is due to inflammation
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of the facial nerve caused by viral neuronitis in the early stages but in later stages it is due to facial nerve edema. In RHS sine herpete, there is peripheral facial palsy without rashes in the ear or mouth. Diagnosis is aided in these cases either by the detection of varicellazoster virus DNA in the middle ear fluid, skin or blood mononuclear cells or the presence of fourfold rise in antibody to varicella-zoster virus. In RHS involvement of cervical nerves is not usual. Our patient had lesions over C2, C3, C4 and C5 dermatomes. Three theories are postulated to explain this: 1) Spread of varicella-zoster virus via CSF or blood; 2) presence of anastomoses between facial nerve and cervical nerves causing spread of the virus and 3) simultaneous activation of the virus in >1 ganglions.4 Herpes occipitocollaris is characterized by lesions on pharynx, palate, retroauricular region and neck, due to reactivation of varicella-zoster virus from ganglia of upper cervical roots, glossopharyngeal and vagus nerves. Our patient had lesions on neck but not on palate, pharynx or retroauricular region. The diagnosis of RHS is based on history and clinical examination alone. CSF analysis or gadoliniumenhanced contrast magnetic resonance imaging (MRI) of the brain has no diagnostic or prognostic value.5 When compared to Bell’s palsy, RHS if left untreated or if treatment is started after 7 days, has poor prognosis and the full recovery rate can be only 10-30%.6 Involvement of ≥1 cranial nerve, advanced age, higher stage of facial paralysis on 1st admission are well-defined prognostic factors for RHS.5 As compared to Bell’s palsy, patients with RHS have more severe paralysis initially and less likelihood of complete recovery.7 In a prospective study conducted on RHS patients, only 14% had developed vesicles after the development of facial paralysis.7 Thus, RHS may be indistinguishable from Bell’s palsy in the early stages. Based on the study conducted by Murakami et al, combination therapy with prednisolone and acyclovir showed better results than with prednisolone alone. Full neurological recovery rate was high (75%) in the combination therapy group and if treatment is started within the first 72 hours.8 Based on this we treated our patient with the combination therapy. Based on the House-Brackmann classification of facial function (Table 1), our patient had Grade V facial weakness on admission. With treatment, she recovered to Grade IV on Day 10. Our patient got medical attention after 96 hours and hence the partial recovery. She is on regular follow-up.
INTERNAL MEDICINE Table 1. House-Brackmann Classification of Facial Function Grade
Characteristics
I. Normal
Normal facial function in all areas
II. Mild dysfunction
Gross Slight weakness noticeable on close inspection May have slight synkinesis At rest, normal symmetry and tone Motion Forehead - Moderate to good function Eye - Complete closure with minimal effort Mouth - Slight asymmetry
III. Moderate dysfunction
Gross Obvious but not disfiguring difference between sides Noticeable (but not severe) synkinesis, contracture or hemifacial spasm At rest, normal symmetry and tone Motion Forehead - Moderate to good movement Eye - Complete closure with minimal effort Mouth - Slightly weak with maximum effort
IV. Moderately Gross severe Obvious weakness and/or disfiguring dysfunction asymmetry At rest, normal symmetry and tone Motion Forehead - None Eye - Incomplete closure Mouth - Asymmetrical with maximum effort V. Severe dysfunction
Gross Only barely perceptible motion At rest, asymmetry Motion Forehead - None Eye - Incomplete closure Mouth - Slight movement
VI. Total paralysis
No movement
CONCLUSION Early diagnosis and treatment of RHS is required for better recovery of the facial weakness, since it is associated with poor recovery if the diagnosis and treatment are delayed. Multidermatomal zoster should provoke the astute physician to look for any underlying immunocompromised state, like diabetes mellitus as diagnosed in our patient. REFERENCES 1. Adour KK. Otological complications of herpes zoster. Ann Neurol. 1994;35 Suppl:S62-4. 2. Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82(11):1341-9. 3. Harbecke R, Oxman MN, Arnold BA, Ip C, Johnson GR, Levin MJ, et al; Shingles Prevention Study Group. A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009;81(7):1310-22. 4. Kayayurt K, Yavasi O, Bilir O, Ersunan G, Giakoup B. A case of Ramsay Hunt syndrome with atypical presentation. Turk J Emerg Med. 2016;14(3):142-5. 5. Jonsson L, Tien R, Engström M, Thuomas KA. Gd-DPTA enhanced MRI in Bell’s palsy and herpes zoster oticus: an overview and implications for future studies. Acta Otolaryngol. 1995;115(5):577-84. 6. Ko JY, Sheen TS, Hsu MM. Herpes zoster oticus treated with acyclovir and prednisolone: clinical manifestations and analysis of prognostic factors. Clin Otolaryngol Allied Sci. 2000;25(2):139-42. 7. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(2):149-54. 8. Murakami S, Hato N, Horiuchi J, Honda N, Gyo K, Yanagihara N. Treatment of Ramsay Hunt syndrome with acyclovir-prednisone: significance of early diagnosis and treatment. Ann Neurol. 1997;41(3):353-7. ■■■■
Orthostatic Hypotension should be Assessed within 1 Minute of Standing, Says Study A study published online July 24, 2017 in JAMA Internal Medicine has suggested that orthostatic hypotension should be assessed within 1 minute of standing. In the study, assessment within 1 minute was associated with higher odds of dizziness and greater risk of falls, fracture, syncope, motor vehicle crash and mortality vs. evaluation after 1 minute.
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OBSTETRICS AND GYNECOLOGY
Transobturator Tape for Female Stress Incontinence: Our Experience M GOPI KISHORE*, AV SAINADH
ABSTRACT Aim: The aim of this study was to evaluate the effectiveness of transobturator tape (TOT), patient satisfaction and morbidity in the treatment of female stress urinary incontinence (SUI). Material and methods: A total number of 48 patients with SUI underwent TOT procedure from January 2013 to December 2016 by outside-in technique. Data related to operative time, postoperative complications and patient acceptance were assessed. Results: Mean age of the patients was 41.3 years and 46 (95.8%) were multiparous. The operative time was 26 ± 4 minutes and catheter was removed on 1 ± 2 days postoperatively. Hospital stay was 2 ± 3 days and return to normal activity was 4-7 days for 46 (95.8%) patients and 7-10 days for 2 (4.2%) patients. Of the 48 patients, 45 (93.75%) were continent postoperatively while 3 (6.25%) patients had occasional urine leak that did not influence daily activities. There was no major intra-/postoperative complication and the quality-of-life improved significantly. A total of 45 (93.75%) patients were completely cured and satisfied, whereas 3 (6.25%) patients improved and were partially satisfied with the surgical outcome. Conclusion: The TOT sling procedure is an effective treatment for SUI with high success rate, high satisfaction rate, low morbidity and short hospital stay.
Keywords: Transobturator tape sling, stress urinary incontinence, complications, tension free
S
tress urinary incontinence (SUI) is an involuntary urine loss due to increased intra-abdominal pressure during exertion, sneezing or coughing. In genuine stress incontinence, there will be hypermobility or lowering of the vesicourethral segment or a combination of two factors but the intrinsic sphincter itself is intact and normal. An estimated prevalence for urinary incontinence is nearly 25-30% in women aged 30-60 years, with approximately half of the cases attributed to SUI. Various factors that may increase the risk of developing incontinence include aging, obesity, smoking, straining, heavy manual labor and chronic obstructive pulmonary disease. The initial treatment for SUI is conservative therapies like lifestyle modifications, pelvic floor muscle training, bladder training and medical treatment. Surgery is indicated for those patients with
*Head Dept. of Urology ESIC Super Speciality Hospital, Sanath Nagar, Hyderabad, Telangana Address for correspondence Dr M Gopi Kishore Head, Dept. of Urology ESIC Super Speciality Hospital, Sanath Nagar, Hyderabad - 38,Telangana E-mail: gkmeda@yahoo.com
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no improvement in symptoms and quality-of-life (QOL) after initial treatment. Numerous surgical methods for stress incontinence have been described. The basic principle in treatment of SUI is proper suspension by creating functional kinking of the mid-urethra during increased intra-abdominal pressure. In the past decade, two minimally invasive sling procedures have been developed. In 1996, Ulmsten introduced the tension free vaginal tape (TVT) procedure and reported an initial 2-year cure rate of 84%.1 TVT is a safe and successful procedure but serious though rare complications like bladder perforation, vascular and bowel injuries have been reported with this technique.2 In order to reduce these complications, Delorme in 2001 reported a transobturator vaginal tape (TOT) approach, which consisted of placing a mesh through the obturator foramen behind the mid-urethra.3 This approach is more anatomically correct and a theoretical advantage is less obstruction and postoperative voiding dysfunction. These minimally invasive mid-urethral sling techniques have become the standard procedures for the surgical treatment of stress urinary incontinence. MATERIAL AND METHODS This study was a prospective study from January 2013 to December 2016, conducted on 48 patients
OBSTETRICS AND GYNECOLOGY diagnosed with genuine SUI, who were managed with transobturator sling in the Dept. of urology, ESIC Super Speciality Hospital, Hyderabad. All patients attending Urology OPD, who complained of involuntary passage of urine on coughing, laughing, straining, were subject to a thorough history taking, physical examination and local examination with Bonneyâ&#x20AC;&#x2122;s test. All baseline and special investigations like urodynamic study and cystopanendoscopy were conducted on the patients. Diagnosis of SUI was based on typical subjective symptoms (i.e., involuntary leakage on effort, exertion, coughing, sneezing or laughing) as recommended in 2002 by the International Continence Society4 and on objective clinical data from the cough stress test, Q-tip test or urodynamic studies. Excluded were women with recurrent urinary tract infections, urge urinary incontinence or mixed urinary incontinence, post-voiding residual (PVR) urine of >150 mL, bladder capacity of <100 mL, co-existing pelvic organ prolapse or any other gynecological problem, previously corrective surgery for stress incontinence, pregnancy and physical or mental impairment. All the patients diagnosed with SUI were explained about their disease, and the available modes of treatment including nonsurgical and surgical options. Patients were managed initially with conservative therapies like lifestyle modifications, pelvic floor muscle training, bladder training and medical treatment (imipramine, duloxetine, estrogens) for 6 months. After failure or not satisfied with conservative management, they were then recruited in this study. TOT procedure was performed in all these patients.
Surgical Technique The American Medical Systems (AMS) Monarc TOT sling was inserted through outside-in route by using the technique recommended by Delorme in 2001. After spinal anesthesia, patient was placed in modified lithotomy position and Foleys catheter introduced to empty the bladder. After retracting the labial fold an incision of 1.5 cm was made 1 cm proximal to the external urethral meatus in the anterior vaginal wall. On both sides, anterior vaginal wall was elevated laterally up to ischiopubic rami taking care of urethra and bladder. Two small skin incisions were made on both sides where the lateral edge of the ischiopubic bone is projected, on the horizontal line that runs through the clitorus. TOT needle was introduced from skin incision and tip of the TOT needle was brought out from the incision
in the vaginal wall with finger acting as a guide. TOT tape was fixed to the tip of the needle. TOT needle was withdrawn through the same path taking along with it one end of the TOT tape through the incision in groin. Same procedure was repeated on the other side also. The sling was placed under the middle of the urethra, tension-free with little finger gap, the two ends of the sling were sectioned at the level of groin skin incision and the vaginal incision was closed. The Foley catheter was kept 24-48 hours postoperatively and the patients were usually discharged 2 days after surgery.
Assessment Postoperative assessment included pain associated with surgery, lower urinary tract symptoms, infection, voiding problem and time to return to normal activity, was done at 1-week, 1-month and 6 months follow-up visits. At 6-month follow-up visit, the patients were evaluated for surgical outcome by cough stress test in full bladder, long-term complications, urinary flow rate, PVR urine, patient satisfaction, QOL index. QOL index assessed by number of incontinence pads used per day or week (scale 1-5 - none, 1-3/day, >3/day, 1-3/week, >3/ week), influence of urinary leak on daily activity (family life, social life, sleep and vacation), frequency of avoiding activities due to fear of urine leak and nonavailability of toilets (scale 1-5 - never, seldom, sometimes, often, always).5 The surgical outcome was divided into 3 groups, including cured, improved and failed. Patients were considered cured if they were extremely satisfied, good QOL, no urine leak, negative cough stress test, no complications, good urine flow rate and <50 mL PVR urine. Patients were considered to have improved if they were satisfied, satisfactory QOL, had occasional urine leakage that did not influence daily activities or require any further treatment, no leakage on the cough stress test, mild complications, satisfactory urine flow rate and post-void 50-100 mL urine. Treatment was considered to have failed if patients were not satisfied, poor QOL, had urine leak, positive cough stress test, complications, poor urine flow and post-void urine >100 mL. RESULTS The total number of patients evaluated in our study was 48. The age of the patients were in the range of 35-48 years and mean age 41.3 years. Out of the total 48 patients, 46 (95.8%) were multiparous. All patients presented with involuntary loss of urine during straining, 41 (85.4%) patients had Grade 2 and duration of symptoms was more than 3 years
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OBSTETRICS AND GYNECOLOGY in 44 (91.6%) patients. Twelve (25%) patients had mild cystocele preoperatively, which resolved after surgery. Associated problems like diabetes mellitus/ hypertension were present in 9 (18%) patients. Bonney test was positive in all cases. Abdominal leak point pressure varied from 96 to 112 cm water. All patients had maximum urine flow rate (MFR) >20 mL/sec and PVR urine <50 mL. The operative time was 26 ± 4 minutes with minimal blood loss of 60 ± 20 mL, which was calculated by using pre-weighed swabs. No major intraoperative complications like urethral or bladder injury were observed. Catheter was removed on 1 ± 2 days postoperatively and hospital stay was 2 ± 3 days. Forty-six (95.8%) patients voided satisfactorily but 2 (4.2%) patients failed to void after catheter removal for which recatheterization done for 3 more days and they voided satisfactorily after catheter removal. Various postoperative complications associated with the procedure, which gradually subsided over few days, are summarized in Table 1. Of the 48 patients, 45 (93.75%) were continent postoperatively while 3 (6.25%) patients had occasional urine leak that did not influence daily activities or required any further treatment and no leakage on the cough stress test. Return to normal activity was 4-7 days for 46 (95.8%) patients and 7-10 days for 2 (4.2%) patients. The QOL index improved from a mean value of 12.6 to a postoperative value of 2.1. Urine flow rate was >20 mL/sec in 39 (81.25%) patients postoperatively Table 1. Postoperative Complications Complications Number Percentage (%) Postoperative pain Wound infection
4 1
8.3 2.08
UTI LUTS - Urgency, dysuria
2 3
4.16 6.25
Hematoma, hematuria Urinary retention
0 2
0 4.16
Mild-obstructive voiding
9
18.75
Vaginal erosion, dyspareunia
0
0
Table 2. Surgical Outcome Outcome
Number
Percentage (%)
Cured
45
93.75
Improved
3
6.25
Failed
0
0
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and 15-20 mL/sec in 9 (18.75%) patients that improved to >20 mL/sec after 3 months. PVR urine was <50 mL in 41 (85.4%) patients and 50-100 mL in 7 (14.6%) patients. A total of 45 (93.75%) patients were satisfied, whereas 3 (6.25%) patients partially satisfied with surgical outcome 6 months follow-up. Table 2 shows the surgical outcome of different patients at follow-up. DISCUSSION The main goal of the surgical treatment of SUI is to restore a perfect continence with minimal morbidity. Surgical procedures for stress incontinence generally aim to lift and support the urethrovesical junction but in the last decade, the emphasis has been on suburethral support at the mid-urethral level.6 Various procedures for suburethral support are transvaginal tape or TVT and transobturator tape or TOT. Delorme in 2001 described the TOT procedure, which involved the tension-free insertion of a polypropylene tape via a tunneler in a horizontal plane under the mid-urethra between the two obturator foramina in an ‘outside-in’ technique, which is an excellent alternative to the retropubic approach that reduces complications.3 There are two basic techniques for performing TOT: ‘outside-in’ as described by Delorme and ‘inside-out’ as described by de Leval.7 In our cases, trocars were placed from outside-in technique as described by Delorme. Subjective cure is usually regarded as the absence of incontinence during cough stress test. In this study, the mean duration of surgery was 26 ± 4 minutes with minimal blood loss of 60 ± 20 mL. Taweel et al reported mean surgery duration of 18 minutes and average intraoperative blood loss of 57 mL, whereas Moore et al reported mean duration of 23 minutes and blood loss of 36 mL in their study.8,9 The average hospital stay of 48 patients in this study was 2.1 days. Isabelle et al, reported the mean hospitalization as 2.2 days. Purnichescu et al from France reported mean duration of hospitalization as 1.25 days.10 In our series of 48 patients, there was no major intraoperative complication like urethral, bladder and neural or vascular injury. Achtari et al showed by cadaveric dissection that transobturator in-out (TVT-O) runs more closely to the obturator canal, making TVT-O more prone to possible injury of the obturator nerve and vessels.11 Houwert et al prospectively studied 191 women and did not find any obturator nerve or vessel injury.12 Pardo Schanz et al, in their 3-year experience with
OBSTETRICS AND GYNECOLOGY 200 patients had 3 intraoperative complications resulting in bladder injury.13 Two (4.2%) patients failed to void after catheter removal in 24 hours probably due to urethral irritation but voided satisfactorily after 3 days. In the early part of our series, 9 (18.75%) patients showed decreased urine flow rate and 7 (4.6%) patients had 50-100 mL PVR urine, which responded to conservative treatment. Sander et al observed that the presence of the tape would decrease the urinary flow and offer increase in resistance to urethra thereby causing retention.14 Ingber et al and Romero-Nava et al have reported that there may be an improvement in the outcomes with time.15,16 Celik et al have reported that voiding disturbance is known to be transient and resolves spontaneously as well.17 Kim et al reported a similar incidence of retention of urine and voiding dysfunction, which responded to conservative treatment.18 In our study, return to normal activity was 4-7 days for 46 (95.8%) patients and 7-10 days for 2 (4.2%) patients. Barry et al, observed faster return to activity in TOT surgery due to short mean operation time, less dissection and natural suburethral suspension when compared with the TVT.19 Various postoperative complications like postoperative pain occurred in 4 (8.3%), lower urinary tract symptoms in 3 (6.25%), wound infection in one (2.08%) and urinary tract infection in 2 (4.16%) patients that resolved after few days. Pardo Schanz et al,13 Taweel et al8 and Latthe et al20 showed similar low postoperative complications ranging from 3% to 8% following TOT surgery, which is comparable with our study. The QOL index in our study improved from a mean value of 12.6 to a postoperative value of 2.1, which is comparable with Paul et al study.5 TOT application was successful in 93.75% cases in this study and improved in 6.25% cases. Delorme in 2001 reported on 40 patients in whom TOT was applied for the first time, 39 patients had no incontinence postsurgery and 1 patient had improvement in symptoms.3 In 2007, Latthe et al quoting their experience in Britain in a series of 135 patients who were applied TOT, reported the subjective level of complete cure and improvement reported by patients were 89.6% and 8.8%, respectively.20 In our study, 93.45% satisfied and 6.25% partially satisfied with the surgical outcome in 6-month follow-up. We found similar satisfaction rates with other studies but subjective cure rate detected in our study was better in comparison with other studies.6,10-13 The results of the present study have confirmed the optimal results in stress incontinence previously reported in short-term studies.
CONCLUSION The TOT sling procedure is an effective treatment for SUI with high success rate, high satisfaction rate, low morbidity and short hospital stay. TOT surgery is welltolerated and accepted by the patients and provides a long-term cure for patients of SUI. Considering it safe, easy to perform, short operating time, quicker return to activities, minimal complications and high success rate, we recommend TOT as the primary choice for the treatment of SUI. REFERENCES 1. Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 1996;7(2):81-5; discussion 85-6. 2. Karram MM, Segal JL, Vassallo BJ, Kleeman SD. Complications and untoward effects of the tensionfree vaginal tape procedure. Obstet Gynecol. 2003;101(5 Pt 1):929-32. 3. Delorme E. Transobturator urethral suspension: miniinvasive procedure in the treatment of stress urinary incontinence in women. Prog Urol. 2001;11(6):1306-13. 4. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Am J Obstet Gynecol. 2002;187(1):116-26. 5. Paul F, Jose A, Giridhar A, Mampatta J, Shetty S, et al. Impact of transobturator tape procedure on quality of life in female stress urinary incontinence. IJARS. 2017;6(1): SO06-SO09. 6. Minaglia S, Ozel B, Hurtado E, Klutke CG, Klutke JJ. Effect of transobturator tape procedure on proximal urethral mobility. Urology. 2005;65(1):55-9. 7. de Leval J. Novel surgical technique for the treatment of female stress urinary incontinence: transobturator vaginal tape inside-out. Eur Urol. 2003;44(6):724-30. 8. Taweel WA, Rabah DM. Transobturator tape for female stress incontinence: follow-up after 24 months. Can Urol Assoc J. 2010;4(1):33-6. 9. Moore RD, Miklos JR. Argentina: Buenos Aires; 2006. Mar 29. Transobturator sling: combined analyses of 1 year follow up in 9 countries with 266 patients. XV Congress of the International Society for Gynecologic Endoscopy. April 1. 10. Purnichescu V, Cheret-Benoist A, EbouĂŠ C, Von Theobald P. Surgical treatment for female stress urinary incontinence by transobturator tape (outside in). Study of 70 cases. J Gynecol Obstet Biol Reprod (Paris). 2007;36(5):451-8. 11. Achtari C, McKenzie BJ, Hiscock R, Rosamilia A, Schierlitz L, Briggs CA, et al. Anatomical study of the
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OBSTETRICS AND GYNECOLOGY obturator foramen and dorsal nerve of the clitoris and their relationship to minimally invasive slings. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17(4): 330-4.
16. Romero-Nava LE, Gómez-Cardoso R. Stress urinary incontinence treatment with modified technique tension-free vaginal tape obturator. Ginecol Obstet Mex. 2015;83(9):537-44.
12. Houwert RM, Renes-Zijl C, Vos MC, Vervest HA. TVT-O versus Monarc after a 2-4-year follow-up: a prospective comparative study. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(11):1327-33.
17. Celik H, Harmanli O. Evaluation and management of voiding dysfunction after midurethral sling procedures. J Turk Ger Gynecol Assoc. 2012;13(2):123-7.
13. Pardo Schanz J, Ricci Arriola P, Tacla Fernández X, Betancourt Ortiz E. Trans obturator tape (TOT) for female stress incontinence. Experience with three years follow-up in 200 patients. Actas Urol Esp. 2007;31(10):1141-7. 14. Sander P, Møller LM, Rudnicki PM, Lose G. Does the tension-free vaginal tape procedure affect the voiding phase? Pressure-flow studies before and 1 year after surgery. BJU Int. 2002;89(7):694-8.
18. Kim S, Bae J, Cho M, Lee K, Lee H, Jun T. Effect of preoperative flow rate on postoperative retention and voiding difficulty after transobturator tape operation. Korean J Urol. 2014;55(3):190-5. 19. Barry C, Lim YN, Muller R, Hitchins S, Corstiaans A, Foote A, et al. A multi-centre, randomised clinical control trial comparing the retropubic (RP) approach versus the transobturator approach (TO) for tensionfree, suburethral sling treatment of urodynamic stress incontinence: the TORP study. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(2):171-8.
15. Ingber MS, Krlin RM, Vasavada SP, Firoozi F, Goldman HB. 20. Outcomes of Midurethral Slings in Women with Concomitant Preoperative Severe Lower Urinary Tract Voiding Symptoms. Ochsner J. 2015;15(3):223-7. ■■■■
Latthe PM, Patodi M, Constantine G. Transobturator tape procedure in stress urinary incontinence: UK experience of a district general hospital. J Obstet Gynaecol. 2007;27(2):177-80.
Risk of Appendiceal Endometriosis Among Women with Deep-infiltrating Endometriosis The goal of a new study published in the International Journal of Gynecology and Obstetrics was to determine whether deep-infiltrating endometriosis (DE) carries a higher risk of appendiceal endometriosis (AppE) than superficial endometriosis or no endometriosis. In this retrospective study, univariate, bivariate and regression analyses were performed on data obtained from an internal database for women who underwent coincidental appendectomy during benign gynecologic surgery from July 2009 to February 2014. The results revealed that endometriosis was diagnosed in 38.2% of these women, while 54.3% had DE. The overall prevalence of AppE was deduced to be 13.2% and the prevalence rates were 11.6% for superficial endometriosis and 39.0% for DE. Additionally, the frequency of AppE was higher among women with DE, abnormal appendix appearance and surgical indication. Furthermore, women with DE had a 5.9 times higher risk of AppE when compared to women without endometriosis, controlling for appendiceal appearance and surgical indication; and 2.7 times higher risk of AppE than those with superficial endometriosis. Hence, it was concluded that women with DE have increased risk of AppE. Thus, it was suggested that coincidental appendectomy should form part of complete endometriosis excision for these patients.
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OBSTETRICS AND GYNECOLOGY
Evaluation of Intrauterine Lesions in Infertile Women by Transvaginal Sonography and Hysteroscopy PRINCY MITTAL*, KHUSHPREET KAUR†, PARNEET KAUR†, ARVINDER KAUR‡, NAVKIRAN KAUR#
ABSTRACT Introduction: Infertility is more of a social problem rather than a medical problem. Hysteroscopy has gained general acceptance as a method for investigation of infertility. Transvaginal sonography (TVS) is an noninvasive modality, which provides imaging of uterus. The present study was aimed to evaluate the accuracy of TVS and hysteroscopy in detection of intrauterine lesions in infertile women. Material and methods: Fifty infertile couples coming to the Dept. of Obstetrics and Gynecology, Government Medical College, Patiala were enrolled for the study and they were evaluated by TVS and hysteroscopy with reference to hysteroscopy as the gold standard method. Results: Intrauterine lesions were found by TVS in 8 (16%) cases. Endometrial polyp was the most common abnormality detected (8%). However on hysteroscopy, intrauterine abnormalities were seen in 10 (20%) cases. Here also, endometrial polyp was the most commonly detected abnormality (10%). So, with reference to hysteroscopy as gold standard method, TVS had 83.30% sensitivity and 100% specificity for detecting intrauterine lesions, while it had 100% positive predictive value (PPV) and 95.20% negative predictive value (NPV). TVS, however, was beneficial in evaluating adnexal pathology. Conclusion: Examination of the uterine cavity is an integral part of any thorough evaluation of an infertile woman; both hysteroscopy and TVS are complementary to each other.
Keywords: Infertility, transvaginal sonography, hysteroscopy
I
nfertility is defined as failure to conceive after 1 year of unprotected intercourse.1 It affects approximately 10-15% of couples in the reproductive age group.2 Female factors account for 40% of cases. Mechanical factors account for almost 30% of all cases of infertility.3 One of these, is the intrauterine environment. Structural pathologies in uterine cavity are well-established factors associated with infertility. It has been established that the implantation of fertilized eggs during spontaneous cycles or of blastocysts during assisted reproductive treatment is affected by the morphology and thickness of the endometrium and by the shape of the uterine cavity.4
*Junior Resident †Professor ‡Associate Professor Dept. of Obstetrics and Gynecology #Professor and Head Dept. of Radiodiagnosis Government Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Parneet Kaur Professor Dept. of Obstetrics and Gynecology Government Medical College, Patiala, Punjab E-mail: parneetkd@yahoo.co.in
Intrauterine lesions have been linked generally to fertility reduction and more especially to implantation failure and miscarriage.5 Intrauterine pathologies responsible for infertility are:6 endometrial polyps, submucosal fibroids, adhesions, uterine malformations, distortion of uterine cavity by fibroid or septum, submucous leiomyomata, mullerian anomalies. Endometrial polyps have been shown to affect 9.4-39.4% of infertile women.7 Research has shown that 18.2% of subjects, in whom in vitro fertilization and embryo transfer (IVF-ET) repeatedly fails, have abnormalities of the uterine cavity.8 Distortion of the uterine cavity by a fibroid or a septum can lead to implantation failure and recurrent early miscarriage.6 Thus, examination of the uterine cavity is an integral part of any thorough evaluation of an infertile couple. There are several methods for assessing the uterine cavity. These are: transvaginal sonography (TVS), hysteroscopy, hysterosalpingography. TVS is simple, easy, fast, noninvasive, painless and cost-effective. Hysteroscopy has advantage of direct visualization of potential lesions, can be paired with biopsy if necessary, duration of stay in hospital is decreased and so is the time taken for treatment.9
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OBSTETRICS AND GYNECOLOGY Complications can be uterine perforation, infection, bleeding, burns and embolism. Thus, the present study was conducted to evaluate the diagnostic efficacy of TVS and hysteroscopy in infertility cases. MATERIAL AND METHODS The study was conducted in Dept. of Obstetrics and Gynecology and Dept. of Radiodiagnosis, Government Medical College and Rajindra Hospital, Patiala, Punjab. Fifty infertile subjects coming to the OPD of Obstetrics and Gynecology department during the year 2013-2014 were enrolled for the study. Inclusion criteria were infertile subjects presenting to OPD and willing to participate after written consent. Exclusion criteria were acute ongoing or recent pelvic infection, late menses without confirmation of absence of pregnancy. The data were collected from subjects fulfilling the inclusion and exclusion criteria. A detailed history was taken on a predesigned proforma and written consent was taken from all the subjects. The thorough workup of an infertile patient was done which was followed by TVS and hysteroscopy.
Transvaginal Sonography TVS was performed in the follicular phase of the menstrual cycle using a transvaginal 7.5 MHz probe of Philips Envision Color Doppler Machine. TVS was done under all aseptic conditions. Proper positioning of the patient was made. Condom and appropriate amount of jelly was put over the probe. Probe was inserted transvaginally and uterus, bilateral ovaries as well as adnexa were assessed. The endometrial cavity was inspected in two perpendicular planes, sagittal and transverse view. Thickness, echo pattern, irregularities and distortion of the endometrium were noted. Uterine cavity abnormalities such as polyps, uterine fibroids and uterine congenital anomalies like septum, adhesions and endometrial hyperplasia were investigated. Ovarian volume, follicular pattern and stromal echogenicity was assessed.
then openings of fallopian tubes, uterine cavity, internal cervical os, cervical canal were inspected and the findings were recorded. Depending upon the recovery of the patient, the patient was discharged on the same day or the next day. In the last, the results were analyzed to evaluate the accuracy of transvaginal sonography and hysteroscopy in infertile women. RESULTS Fifty subjects were assessed in this clinical study. Out of 50 cases of infertility, 31 (62%) were of primary infertility and 19 (38%) were of secondary infertility. The mean age of subjects was 27.9 Âą 3.53 years. Regarding duration of infertility, out of primary infertility cases, 5 (16.1%) presented within 2 years, 19 (61.3%) in 2-5 years and 7 (22.6%) after 5 years of marriage. Out of secondary infertility cases, 5 (26.3%) presented within 2-5 years and 14 (73.7%) after 5 years of marriage. On assessment of uterine cavity by TVS (Table 1), out of 50 subjects, 8 (16%) subjects had intrauterine lesions and 42 (84%) had normal uterine cavity. Intrauterine polyp was the commonest finding detected on TVS, it was found in 4 (8%) subjects. Among these, 1 was of primary infertility and 3 were of secondary infertility. Calcification was detected in 1 (2%), congenital abnormality in 1 (2%) and fibroid was present in 2 (4%) of the subjects. Hysteroscopic findings (Table 2) showed intrauterine polyp in 5 (10%) subjects, 2 were of primary infertility and 3 of secondary infertility. This was the most common finding on hysteroscopy. The other lesions seen were adhesions and calcification in 1 case each of secondary infertility. Calcification detected by TVS came out to be bony speck on hysteroscopy (history of D&C due to missed abortion 3 years back). Congenital abnormality in Table 1. Transvaginal Sonography Findings Primary Secondary Total infertility infertility
Percentage (%)
Polyps
1
3
4
8
Hysteroscopy
Adhesions
-
-
-
-
The procedure was performed under anesthesia. The patient was cleaned and draped. P/V examination was done to know the size and position of uterus. Cervix was dilated with metal dilators. Once the cervix was dilated, the hysteroscope was inserted through the cervix into the uterus. The normal saline was used as distention media. First the fundus was inspected and
Calcification
-
1
1
2
Congenital abnormality
1
-
1
2
Submucous fibroid
1
1
2
4
Total
3
5
8
16
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OBSTETRICS AND GYNECOLOGY Table 5. Co-incidental Findings Detected on TVS
Table 2. Hysteroscopic Findings Primary Secondary Total Percentage infertility infertility (%)
Findings
Primary infertility
Secondary infertility
Polyps
2
3
5
10
Right cystic adnexal mass
1
-
Adhesions
-
1
1
2
PCOD
1
-
Calcification
-
1
1
2
Congenital abnormality
1
-
1
2
Submucous fibroid
1
1
2
4
Total
4
6
10
20
Table 3. Findings on TVS and Hysteroscopy Findings
TVS
Hysteroscopy
4 (8%)
5 (10%)
Adhesions
-
1 (2%)
Congenital abnormality
1 (2%)
1 (2%)
Submucous fibroid
2 (2%)
2 (4%)
Calcification
1 (2%)
1 (2%)
Total
8 (16%)
10 (20%)
Polyps
Table 4. Intrauterine Abnormalities Detected by TVS and Hysteroscopy in Infertility Cases Findings
Primary infertility
Secondary infertility
Normal
27 (87.1%)
13 (68.4%)
Polyps
2 (6.5%)
3 (15.8%)
Adhesions
-
1 (5.3%)
Congenital abnormality
1 (3.2%)
-
Submucous fibroid
1 (3.2%)
1 (5.3%)
-
1 (5.3%)
31 (100%)
19 (100%)
Calcification Total
form of uterine septum was seen in 1 case of primary infertility. Submucous fibroids were detected in two subjects, 1 was of primary infertility and another was of secondary infertility. Comparison of finding on TVS and hysteroscopy (Table 3) showed that TVS had detected intrauterine findings in 8 (16%) subjects and hysteroscopy had detected abnormal findings in 10 (20%) subjects. Four (8%) polyps were detected by TVS, whereas hysteroscopy detected 5 (10%) polyps. Hysteroscopy detected intrauterine adhesions in
PCOD = Polycystic ovarian disease.
Table 6. Diagnostic Accuracy of TVS in Detecting Intrauterine Lesions Sensitivity
83.30%
Specificity
100%
PPV
100%
NPV
95.20%
PPV = Positive predictive value; NPV = Negative predictive value.
1 subject which was missed by TVS. Other intrauterine lesions were congenital abnormality in form of uterine septum and calcification detected by both TVS and hysteroscopy. Submucous fibroids were also detected by both TVS and hysteroscopy as shown above. Table 4 shows the relation of uterine cavity abnormalities with the type of infertility regarding primary and secondary infertility. Only 4 subjects (12.9%) of primary infertility had uterine cavity abnormalities. Two subjects (6.5%) had uterine polyps, 1 (3.2%) had congenital abnormality, 1 (3.2%) had submucus fibroid while 6 subjects (31.6%) had uterine cavity abnormality in secondary infertility cases. Three subjects (15.7%) had uterine polyp, 1 (5.3%) had adhesions, 1 (5.3%) had submucous fibroid, 1 (5.3%) had calcification. TVS had additional benefits as adnexa could also be evaluated as shown in Table 5. Table 6 demonstrates the diagnostic accuracy of TVS in detecting intrauterine lesions. Considering hysteroscopy as the gold standard modality, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TVS was 83.3%, 100%, 100%, 95.2%, respectively. DISCUSSION Infertility is a major problem affecting at least 10-15% of couples in reproductive age group. The present study included 31 (62%) cases of primary and 19 (38%) cases of secondary infertility. This was consistent with the studies of Khamesra and Gupta (2009),10 El-Huseiny and Soliman (2013)11 but our findings differs from study done by Sersam LW (2007)12 in whose study secondary infertility case were in majority. The mean
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OBSTETRICS AND GYNECOLOGY age in present study was 27 ± 3.53 years which was in concordance with the studies done by Sersam LW (2007)12 and El-Huseiny and Soliman (2013).11 In the present study, 8 (16%) cases had intrauterine abnormalities as detected by TVS which was in agreement with study done by Sersam LW (2007),12 whereas studies done by Loverro (2001)13 and Khamesra and Gupta (2009)10 showed higher incidence, which may be because of their larger sample size. Hysteroscopy could detect intrauterine abnormalities in 10 (20%) cases in present study which is in concordance with studies of Sersam LW (2007)12 and El-Huseiny and Soliman (2013),11 whereas studies done by Khamesra and Gupta (2009)10 showed higher incidence. Polyps, 4 (8%) was the most common intrauterine abnormality detected by TVS. This was in agreement with the studies done by Sersam LW (2007)12 and Khamesra and Gupta (2009).10 Polyps, 5 (10%) was the most commonly detected intrauterine abnormality by hysteroscopy. This was in agreement with the study done by Sersam LW (2007)12 but the study of Khamesra and Gupta (2009)10 showed lesser incidence. In the present study, endometrial polyps, 2 (6.5%) was commonly detected intrauterine abnormality in primary infertility. This was consistent with the study of Sersam LW (2007).12 In our present study, endometrial polyps, 3 (15.7%) was a commonly detected intrauterine abnormality in secondary infertility. This was in agreement with the study of Sersam LW (2007).12 Considering hysteroscopy as a gold standard, present study had 100% specificity which was in concordance with study of Bettocchi et al (2008),14 but other studies shows lower incidence of specificity. Sensitivity of the present study was 83.3% which was in concordance with study of Khamesra and Gupta (2009)10 and Loverro (2001),13 but other studies shows higher sensitivity. PPV of the present study, 100% was in concordance with the studies of Bettocchi et al (2008)14 and Loverro et al (2001)13 and the NPV (95.2%) was in concordance with Bettocchi et al (2008),14 but other studies shows lower incidence of PPV and NPV, except study of Shalev et al (2000),15 which showed 100% negative value. The present study demonstrated that TVS is effective in accurately diagnosing polyps, fibroids, septa and calcification, while hysteroscopy offers both diagnostic and therapeutic opportunities. On the other hand, TVS also plays an important role in the evaluation of infertile couples for the assessment of ovulatory disorders and early detection of adnexal
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pathology including ovarian cysts, polycystic ovaries. TVS was well-tolerated by the patients and had an acceptable rate in concordance with the classical gold standard “hysteroscopy”. CONCLUSION TVS is a noninvasive, painless and acceptable investigation for use in infertility. It is less expensive than diagnostic hysteroscopy. TVS should be used to assess whether hysteroscopic evaluation of endometrial cavity is indicated. In infertile subjects, hysteroscopy may be used as second step in cases in which TVS gives doubtful results. Thus, TVS may be used as initial diagnostic procedure to select subjects for hysteroscopy. However, hysteroscopy as a confirmatory procedure is suggested if false negative result is suspected. Hence, both modalities are complementary to each other. REFERENCES 1. Hajishafiha M, Zobairi T, Zanjani VR, GhasemiRad M, Yekta Z, Mladkova N. Diagnostic value of sonohysterography in the determination of fallopian tube patency as an initial step of routine infertility assessment. J Ultrasound Med. 2009;28(12):1671-7. 2. Speroff L, Fritz M. Clinical Gynecologic Endocrinologic and Infertility. 8th Edition, Lippincott Williams & Wilkins; 2011;27:1137. 3. Eisenstat SA, Ziporyn T. The Harvard Guide to Women’s health. New Haven (CT): Harvard University Press; 1998. pp. 326. 4. Gonen Y, Casper RF, Jacobson W, Blankier J. Endometrial thickness and growth during ovarian stimulation: a possible predictor of implantation in in vitro fertilization. Fertil Steril. 1989;52(3):446-50. 5. Pérez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L, Alvarez P, et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod. 2005;20(6):1632-5. 6. Lashen H. Female infertility. In: Luesley DM, Baker PN (Eds.). Obstetrics and Gynaecology: An Evidencebased Text for MRCOG. 1st Edition, London: Arnold; 2004. pp. 568. 7. Melki LA, Oliveira MA, Oliveira HC. Can transvaginal sonography avoid the diagnostic complementary hysteroscopy in the detection of the endometrial polyp? Braz J Video-Surg. 2008;1(2):71-5. 8. Syrop CH, Sahakian V. Transvaginal sonographic detection of endometrial polyps with fluid contrast augmentation. Obstet Gynecol. 1992;79(6):1041-3.
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OBSTETRICS AND GYNECOLOGY
Evaluation of Patwardhan Technique in Second Stage Cesarean Section RITA THAKUR*, RITU SHARMA, AJAY WAKHLOO, DINESH GUPTA
ABSTRACT Objectives: The study was conducted to compare the fetomaternal outcome associated with Patwardhan technique and conventional method to extract the deeply impacted head during lower segment cesarean sections. Material and methods: Prospective study was done on 100 cases with single fetus where cesarean section was done during second stage with head deeply impacted in pelvis. Patwardhan technique was adopted in 50 cases (study group) and compared with 50 cases (control group), where conventional method was used. Results: The study shows that only 10% of the patients in the study group, while 68% patients in the control group suffered complications. Postpartum hemorrhage was the major complication in both the groups and occurred in 6% of patients in study group and 36% in control group. The vertical and transverse extension of uterine incisions, bladder injuries and need for blood transfusions were more in the control group. Perinatal outcome was almost similar in both the groups. Conclusion: Patwardhan technique is a safe and appropriate method of delivery during second stage lower segment cesarean section in patients with deeply impacted head to reduce the maternal and fetal morbidity.
Keywords: Patwardhan technique, deeply impacted head, cesarean section
C
esarean deliveries done in the second stage of labor account for one-fourth of all primary cesarean sections.1 Cesarean section at full dilatation is technically difficult because the head is deep in the pelvis with totally drained liquor and is associated with increased incidence of maternal and fetal morbidity. There is risk of trauma to the lower uterine segment and adjacent structures.2 Extension of the uterine incision laterally tearing the uterine blood vessels or vertically downwards into the bladder and even vagina, can cause torrential hemorrhage, which is difficult to control. Our hospital is a tertiary care teaching hospital with a vast referral area. Many patients are referred from periphery in advanced stage of obstructed labor.
of maternal morbidity in the form of uterine incision extension, postpartum hemorrhage (PPH) and fever.3,4 Patwardhan technique is a unique technique which is used for delivering babies in the second stage cesarean section.5,6 We have used Patwardhan technique for delivery of the baby during second stage lower segment cesarean section and compared it with conventional method of delivery. MATERIAL AND METHODS
Extraction of the deeply impacted fetal head may be done by ‘Push method’ i.e., pushing through vagina or by ‘Pull method’ i.e., reverse breech technique. Both these methods are associated with an increased rate
This was a prospective study of 100 woman with single fetus with vertex presentation admitted to the labor room in our hospital from January 2016 to April 2017, where cesarean section was done during second stage with the head deeply impacted in the pelvis. The study group consisted of 50 cases of impacted fetal head that were delivered by ‘Patwardhan technique’ and the control group consisted of 50 cases delivered by ‘Push and Pull’ method.
*Lecturer Dept. of Obstetrics and Gynecology Govt. Medical College, Jammu, J&K Address for correspondence Dr Rita Thakur H. No. 53, Vishwabharati Colony, Lower Muthi, Jammu, J&K
Inclusion criteria in our study: Single fetus with vertex presentation with deeply impacted fetal head due to (a) deep transverse arrest, (b) obstructed labor, (c) mid-pelvis and outlet obstruction. We didn’t include any case of occipito-posterior in our study. Both the groups were compared in terms of maternal outcomes as uterine incision extension, postpartum hemorrhages,
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OBSTETRICS AND GYNECOLOGY blood transfusions and neonatal outcomes in terms of their weight, birth asphyxia and stillbirths. In Patwardhan technique, the incision is made over lower uterine segment at the level of the anterior shoulder of the baby as the head is deeply impacted in the pelvis. Anterior shoulder is now delivered along with the anterior arm by hooking a finger in the elbow. Posterior shoulder is rotated forward and is similarly delivered. Next, the surgeon holds the trunk of the baby gently with both thumbs parallel to spine and with fundal pressure given by assistant, the buttocks are delivered followed by legs. Now the head is gently lifted out of the pelvis by traction on the legs. RESULTS Total of 100 women with single fetus with vertex presentation who underwent second stage cesarean section from January 2016 to April 2017 were included in the study. Fifty patients belonged to the study group delivered by Patwardhan technique and 50 patients belonged to control group who were delivered by conventional method. Obstetric features like maternal age, gestational age, parity and hemoglobin were compared between the two groups. As shown in Figure 1, the majority of the patients in the study were in the age group of 20-25 years (74% in the study group and 70% in the control group). Similarly, the majority of the patients were primigravida in both groups (80% in the study group and 76% in the control group); 74% patients in the study group and 78% in the control group were between 37-40 weeks of gestation as shown in Table 1.
Period of gestation
Study group (n = 50)
Control group (n = 50)
4 (8%)
5 (10%)
37-40 weeks
37 (74%)
39 (78%)
>40 weeks
9 (18%)
6 (12%)
<37 weeks
Table 2. Intraoperative Features Lower segment Normal Distended Impending rupture Total
Study group (n = 50)
Control group (n = 50)
2 (4%)
2 (4%)
44 (88%)
40 (80%)
4 (8%)
8 (16%)
50
50
Table 3. Intraoperative Complications Control group (n = 50)
45 (90%)
16 (32%)
Extension of lower segment incision
1 (2%)
11 (22%)
80
Transverse vertical
0
2 (4%)
70
Excessive bleeding
Study group
90
Percentage (%)
Table 1. Period of Gestation
Study group (n = 50)
Tables 2 and 3 show the status of the lower uterine segment and intraoperative complication, respectively Control group
60
Intraoperative complications None
50
Traumatic
1 (2%)
14 (28%)
40
Atonic
2 (4%)
4 (8%)
Bladder injury
None
2 (4%)
Blood transfusion needed
3 (6%)
17 (34%)
Dislocation of shoulder joint
1 (2%)
None
Hysterectomy
None
1 (2%)
30 20 10 0
20-25 years
More than 25 years Age
Primigravida
Multigravida
Parity
Figure 1. Demographic data.
270
of both the groups. The lower uterine segment features were comparable in both the groups. In majority of the patients, the lower uterine segment was distended (88% in the study group and 80% in the control group). The study shows that only 10% of the patients in the study group while 68% patient in the control group suffered complications. In both the groups, PPH was a major surgical complication (6% in the study group and 36% in the control group). No vertical and 2% lateral extensions of the lower uterine segment incision were seen in the study group, while in the control group 4% had vertical extensions and 22% had lateral extensions. Two (4%) patients in the control group had bladder
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OBSTETRICS AND GYNECOLOGY Table 4. Fetal Outcome Fetal features
Study group (n = 50)
Control group (n = 50)
3 (6%)
3 (6%)
2.5-3.5
42 (84%)
44 (88%)
>3.5
5 (10%)
3 (6%)
Nil
28 (56%)
25 (50%)
Mild-to-moderate
Fetal weight (kg) <2.5
Asphyxia 20 (40%)
22 (44%)
Severe
1 (2%)
1 (2%)
Stillbirth
1 (2%)
2 (4%)
injury, while no case of bladder injury was seen in the study group. It was seen that 34% patients in the control group needed blood transfusion, while only 6% needed blood transfusion in the study group. Hysterectomy was required in 1 patient in the control group, while no patient needed hysterectomy in the study group. One case of shoulder dislocation was seen in the study group, which was due to manual rotation of posterior shoulder anteriorly in case of deep transverse arrest. Table 4 shows that the weights of the babies in the two groups were almost similar. Majority of the fetuses were between 2.5-3.5 kg in both the groups (84% in the study group and 88% in the control group). This means that if any of the two groups had more complications, they were unrelated to the birth weight of the child. Fetal asphyxia was comparable in both the groups. No fetal asphyxia occurred in 56% of babies in the study group and 50% in the control group, whereas mild-tomoderate asphyxia was seen in 40% and 44% in both the groups, respectively. Severe fetal asphyxia was seen in 2% in both groups and stillbirth was also comparable (2% and 4% in study group and control group). DISCUSSION The burden of maternal and fetal complications during cesarean section in deeply impacted (wedged) head is high. Many of these complications are preventable. The study was performed to compare the fetomaternal outcome and complications of Patwardhan technique and conventional methods, for delivery of deeply impacted head during cesarean section. Obstetric features like maternal age, parity, gestational age and hemoglobin were comparable in both the groups. Lower uterine segment was found stretched and distended in 88% of patients in the study group
and 80% in the control group. This is comparable with the study conducted by Bairwa et al in which lower uterine segment was stretched in 84% in study group and 80% in control group.7 Features of impending rupture of uterus were found in 8% and 16% of study and control group, respectively. This is again comparable with study conducted by Bairwa et al in which impending rapture was found in 12% and 18% of study and control group patients, respectively.7 In this study, 90% patients of the study group and 32% of the control group had no intraoperative complications. This is in comparison with study conducted by Patwardhan et al, Khosla et al, Bairwa et al, Desai et al and Mukhopadhyay et al.5-9 Vertical extension of lower uterine segment incision was not seen in study group, while 4% patients had it in control group. It is comparable to study conducted by Khosla et al in which there was no vertical extension in the study group but it was 4.5% in the control group.6 Lateral extension was found in 2% patients in the study group and 22% patients in the control group. These findings were nearly comparable to study conducted by Khosla et al in which lateral extension was found in 24.1% in the control group and none in the study group.6 In the study group, only 2% patients had traumatic PPH, while 4% had atonic PPH. In contrast, in control group 28% of patients had traumatic PPH and 8% had atonic PPH. These findings correlated with improved maternal prognosis after using Patwardhan technique. In the study conducted by Mukhopadhyay et al,9 only 2% patients experienced traumatic PPH in the study group as compared to 42% in the control group. In the present study, most of the babies delivered weighed between 2.5-3.5 kg (84% in the study group and 88% in the control group). These findings are comparable to the study conducted by Khosla et al6 and Desai et al.8 Fetal asphyxia was not seen in 56% babies in the study group and 50% in the control group, whereas mild-to-moderate asphyxia was seen in 40% and 44% in the study group and control group, respectively. The difference is comparable to the study conducted by Bairwa et al.7 Severe asphyxia was found in 2% patients in both the groups. Birth asphyxia and stillbirth rates were almost similar in two groups indicating that, the technique of delivery was not responsible for these. But Desai et al reported that the incidence of birth asphyxia was significantly more in the control group.8 In the present study, 6% patients in the study group and 34% in the control group needed blood transfusions. The results are comparable to study conducted by
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OBSTETRICS AND GYNECOLOGY Mukhopadhyay et al in which 8% patients in the study group and 34% in the control group required blood transfusions.9 The increased requirement of blood transfusions in the control group clearly shows that maternal outcome is improved with the Patwardhan technique. CONCLUSION Patwardhan technique needs expertise but has minimum complications and can be learnt easily by practice. It is safe and an appropriate method of delivery during lower segment cesarean section in patients with deeply impacted head to reduce the maternal and fetal morbidity. This technique needs to be more widely utilized and publicized. REFERENCES 1. Evaluation of cesarean delivery, the American College of Obstetricians and Gynecologist: Women’s Health Care Physicians.
3. Sung JF, Daniels KI, Brodzinsky L, El-Sayed YY, Caughey AB, Lyell DJ. Cesarean delivery outcomes after a prolonged second stage of labor. Am J Obstet Gynecol. 2007;197(3):306.e1-5. 4. Alexander JM, Leveno KJ, Rouse DJ, Landon MB, Gilbert S, Spong CY, et al; National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Comparison of maternal and infant outcomes from primary cesarean delivery during the second compared with first stage of labor. Obstet Gynecol. 2007;109(4):917-21. 5. Patwardhan BD, Motashaw ND. Caesarean section. J Obstet Gynecol India. 1957;8:1-15. 6. Khosla AH, Dahiya K, Sangwan K. Cesarean section in a wedged head. Indian J Med Sci. 2003;57(5):187-91. 7. Bairwa R, Garg GS, Agarwal M, Chittora SP. Delivery of baby in obstructed labour by Patwardhan technique - an observational study. Int J Med Sci Educ. 2016;3(2):132-40. 8. Desai P, Shah N. Preventing complications by “Shoulder First” method of delivery in cases of obstructed labour. J Obstet Gynecol India. 2001;51:91-4.
9. 2. Revah A, Ezra Y, Farine D, Ritchie K. Failed trial of vacuum or forceps - maternal and fetal outcome. Am J Obstet Gynecol. 1997;176(1 Pt 1):200-4. ■■■■
Mukhopadhyay P, Naskar T, Dalui R, Hazra S, Bhattacharya D. Evaluation of Patwardhan’s technique: A four year study in rural teaching hospital. J Obstet Gynecol India. 2005;55(3):244-6.
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Ozturk E, Ugur MG, Balat O, Kutlar I, Dikensoy E, Cebesoy B. An analysis of hysteroscopy experience over a sevenyear period. Clin Exp Obstet Gynecol. 2010;37(2):150-1.
10. Khamesra A, Gupta S. Transvaginal sonography of the uterine cavity with hysteroscopic correlation in the assessment of infertile women. Int J Gynecol Obstet. 2009:396-8. 11. El-Huseiny AM, Soliman BS. Hysteroscopic findings in infertile women: a retrospective study. Mid East Fertil Soc J. 2013;18(3):154-8. 12. Sersam LW. The value of transvaginal sonography performed before diagnostic hysteroscopy for the evaluation of uterine cavity in infertile women. Iraqi Postgrad Med J. 2007;6(4):276-85.
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13. Loverro G, Nappi L, Vicino M, Carriero C, Vimercati A, Selvaggi L. Uterine cavity assessment in infertile women: comparison of transvaginal sonography and hysteroscopy. Eur J Obstet Gynecol Reprod Biol. 2001;100(1): 67-71. 14. Bettocchi S, Nappi L, Sardo ADS, Greco E, Guida M, Sorrentino F, et al. Effectiveness of hysteroscopy versus transvaginal ultrasound in diagnosing intra-uterine lesions in infertile women. Euro Obstet Gynaecol. 2008;3(1):12-4. 15. Shalev J, Meizner I, Bar-Hava I, Dicker D, Mashiach R, Ben-Rafael Z. Predictive value of transvaginal sonography performed before routine diagnostic hysteroscopy for evaluation of infertility. Fertil Steril. 2000;73(2): 412-7.
EXPERTâ&#x20AC;&#x2122;S VIEW
How to Manage Hypertension in a Patient with Acute Heart Attack? KK AGGARWAL
I
n patients with acute myocardial infarction (AMI), the prevalence of antecedent hypertension varies from 31% to 59%.1,2 However, it is not clear whether previously known hypertensive patients have an increased rate of adverse outcomes after AMI including stroke, heart failure and cardiovascular death.3 Conversely, in non-ST elevation AMI (NSTEMI), hypertension is an independent factor for major shortand long-term cardiac adverse outcome.4
In a patient presenting with AMI and severe hypertension, the reduction of blood pressure (BP) should not be abrupt, and a gradual reduction over a period of 24-48 hours is recommended, so that further myocardial or brain ischemia is avoided.5 The appropriate treatment should include the initiation of intravenous nitrates, with intravenous labetalol, sodium nitroprusside and/or nicardipine as alternatives, especially in very severe hypertension or hypertensive emergencies. Sublingual nifedipine, which has usually been considered as a first-line drug, should be avoided, in view of the negligible oral absorption and unpredictable hypotensive effects.5 In the majority of patients presenting as an emergency with AMI and hypertension without signs of other acute target organ damage, hypertension does not necessarily represent an acute major threat. Treatment should be aimed at relieving symptoms, protecting the ischemic but potentially viable myocardial tissue and reducing mortality. BP should be reduced to <160/110 mmHg before administration of thrombolysis, although if available, primary angioplasty is an option for reperfusion in patients with high BP and/or the perceived risk of stroke if thrombolysis is unacceptable.5 Oral or intravenous b-adrenoceptor blockers lower the BP within hours. They also have important antiischemic effects, so that they should be considered as
Group Editor-in-Chief, IJCP Group President, Heart Care Foundation of India
first-line therapy in patients with myocardial infarction, in the absence of contraindications.5 These drugs exert a protective effect on the ischemic myocardial tissue by reducing oxygen demand by 15-30%. Moreover, the b-blockers have antiarrhythmic properties and cause favorable shunting of blood away from nonischemic to ischemic regions. In the presence of chronic ischemia, b-blockers can also increase the ejection fraction, particularly during exercise and improve left ventricular (LV) function.5 Angiotensinconverting enzyme (ACE) inhibitors are recommended for use in all patients after myocardial infarction (MI). Two major trials, the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) study, showed the cardioprotective effect of ACE inhibitor in hypertensive coronary heart disease (CHD) patients.6-9 In the EUROPA study, 12,218 patients were randomized to treatment with an ACE inhibitor (perindopril) or placebo. Individuals in the perindopril group had significantly less MI, cardiovascular system (CVS) death or cardiac arrest.6 The HOPE study involved 9,297 patients with CVS risk factors, who were randomized to ramipril or placebo. Approximately half of the study population had hypertension. Ramipril therapy was associated with small (3/2â&#x20AC;&#x2030; mmHg) reduction in BP but significant reduction in CVS death, stroke and MI.7,8 These cardioprotective effects were initially thought to be independent of BP control, until a subgroup analysis of the HOPE trial revealed a significant reduction in 24-hour ambulatory BP with ramipril that was not found in the main trial that measured only office BP.9 ACE inhibitors are indicated for all hypertensive patients with AMI who have no contraindications, especially if there is associated depressed LV systolic function (left ventricular ejection fraction [LVEF] <40%).10,11 From the trials available in patients presenting with AMI with hypertension, calcium
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EXPERT’S VIEW channel blockers like verapamil and probably diltiazem can be used as third-line drugs, after b-blockers, ACE inhibitor and nitrates, for treating hypertension during an AMI, if LV function is preserved. REFERENCES 1. Willich SN, Müller-Nordhorn J, Kulig M, Binting S, Gohlke H, Hahmann H, et al; PIN Study Group. Cardiac risk factors, medication, and recurrent clinical events after acute coronary disease; a prospective cohort study. Eur Heart J. 2001;22(4):307-13. 2. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-52. 3. Thune JJ, Signorovitch J, Kober L, Velazquez EJ, McMurray JJ, Califf RM, et al. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-risk myocardial infarction. Hypertension. 2008;51(1):48-54. 4. Dumaine R, Gibson CM, Murphy SA, Southard M, Ly HQ, McCabe CH, et al; Thrombolysis in Myocardial Infarction (TIMI) Study Group. Association of a history of systemic hypertension with mortality, thrombotic, and bleeding complications following non-ST-segment elevation acute coronary syndrome. J Clin Hypertens (Greenwich). 2006;8(5):315-22.
6. Fox KM; EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782-8. 7. The Heart Outcomes Prevention Evaluation Study Investigators. Yusuf S, Sleight P, Pogue J, Bosch J, Davis K, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-53. 8. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:1376. 9. Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy. Hypertension. 2001;38(6):E28-32. 10. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation. 1998;97(22):2202-12.
11. Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor 5. Lip GY, Lydakis C, Beevers DG. Management of patients Myocardial Infarction Collaborative Group. Lancet. with myocardial infarction and hypertension. Eur Heart J. 2000;21(14):1125-34. 2000;355(9215):1575-81. ■■■■
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MEDILAW
Onus to Prove Medical Negligence or Deficiency Lies on the Complainant
The complainant has alleged that because of the wrong treatment and gross negligence on the part of respondent/ doctors the baby was severely retarded both mentally and physically.
There is no material produced by the complainant to show any lapse or deficiency in service on the part of the respondents in either not diagnosing or prescribing medical treatment.
Proceed
I had explained the complainant through diagrams and medical literature showing the possibility of the child being mentally retarded whereas the complainant did not follow the medical advice and rather started consulting some other persons.
Lesson: In its order in the First Appeal No. 490 of 2007 NCDRC stated that the appellant has not been able to prove through any credible evidence that there was medical negligence or deficiency on the part of the respondents or any action or omission on their part which resulted in or aggravated the congenital condition of the infant. On the other hand, there is credible evidence that right through the prenatal period and after the birth due medical attention and proper treatment was given by both respondents who are well-qualified specialists in their fields. We agree with these findings and therefore, uphold the order of the State Commission. The first appeal is dismissed.
COURSE OF EVENTS ÂÂ
This first appeal has been filed by the complainant before the State Commission and appellant herein, being aggrieved by the order of the State Consumer Disputes Redressal Commission, Delhi (hereinafter referred to as the ‘State Commission’) which has rejected his complaint of medical negligence against Respondents No. 1 and 2, respectively.
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In his complaint to State Commission, appellant had contended that his wife delivered a male child at Shubham Hospital, New Delhi and the delivery was handled by Respondent No. 1 who was a Gynecologist and thereafter by Respondent No. 2, a Pediatrician.
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The appellant had alleged that because of the wrong treatment and gross negligence on the part of respondent/doctors the baby was severely retarded both mentally and physically.
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The appellant had specifically stated that his wife who was suffering from fever in her 32-34 weeks of pregnancy had visited Respondent No. 1 who failed to conduct a basic test known as TORCH test, which would have clearly indicated the nature of the prenatal viral infection and whether it had infected the fetus. Instead the patient was given only paracetamol to check the fever.
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The baby was born after 36 weeks of gestation i.e., 4 weeks before the full gestation period with symptoms of the present disease but he was not given the required medical treatment at birth as a result of which, as per the certificate issued by the All India Institute of Medical Sciences (AIIMS) in 1996, he has cerebral palsy with spastic tendencies, mental retardation and 90% permanent physical impairment.
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The certificate from AIIMS specifically stated that the perinatal viral infection was the cause of this condition. If due medical treatment had been
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MEDILAW given at birth instead of just tonics and vaccines by Respondent No. 2, appellant contended that the extent of disability would not have been so extensive. ÂÂ
Appellant, therefore, approached the State Commission on ground of medical negligence and requested that respondents be directed to pay him ` 15 lakhs as compensation for mental agony and to enable him to provide the necessary treatment for his child.
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Respondents filed a written rejoinder denying that there was any medical negligence in the care and treatment of the appellant’s wife and infant.
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The appellant’s wife approached Respondent No. 1 for prenatal treatment for the first time in December, 1991 and she was accordingly advised necessary tests including ultrasound and no abnormalities were detected.
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In her 32-34 weeks of pregnancy the appellant’s wife had fever and was prescribed crocin to control the fever and no other drug.
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Growth retardation of the baby was noted at 34-35 weeks and the appellant’s wife was advised bed rest.
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The appellant’s wife was brought to the hospital in the 36th week in advanced labor and delivery took place within 1 hour with the umbilical cord wound thrice around the baby’s neck and he had passed meconium because of which there was difficulty in spontaneous initiation of breathing at birth but the baby was successfully resuscitated within 2 minutes with normal Apgar count. Since, the baby was small for date, he was kept in a thermoneutral environment under an oxygen hood and prescribed prophylactic antibiotics and also medication for the mild jaundice which is common in newborns.
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The baby was discharged on 24.06.1992 in a suitable condition.
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On 03.07.1992, the baby was brought to the hospital with complaints of vomiting, lethargy and disinterest in suckling and Respondent No. 2 after examining him advised hospitalization, which was not accepted by the appellant who thus acted against medical advice.
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On 01.08.1992 during another visit, spastic tendencies were visible and Respondent No. 2 explained the medical condition as also the prognosis to the parents and advised them to bring the baby for follow-up visit within 7 days but the baby was brought only after 21 days in poor medical
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condition. Amoxicillin for 10 days was prescribed but the parents discontinued the antibiotics after 3 days. Thereafter, the parents never brought the child to the respondent and probably got him treated elsewhere. There was thus no medical negligence in the treatment of either the mother or the baby and it was the appellant and his wife who repeatedly failed to follow medical advice. ÂÂ
It was also contended that the first appeal was time barred as it was filed beyond the statutory period of 2-year from the date on which the cause of action had arisen.
ORDER OF THE STATE COMMISSION ÂÂ
The State Commission after hearing both parties and on the basis of evidence filed before it concluded that no case of medical negligence was made out. The relevant part of the order of the State Commission is reproduced:
Here is a case where the child was born at 36 weeks gestation on 16-06-1992. The last when the complainant contacted the OP was till 15, September, 1992. The child subsequently has been diagnosed as suffering from cerebral palsy in 1996, which is indication of mental retardation. The complainant was advised hospitalization of the child but he declined. Medical treatment prescribed was not followed. There is no cure for cerebral palsy. TORCH test is prescribed only if the mother is suffering from such fever in the first 12 weeks of pregnancy and not 34 weeks of pregnancy. Giving PCM (Paracetamol) to a mother who is in 34 weeks of pregnancy is absolutely safe and by no means can cause any kind of infection or abnormality to the child. The mental retardation of the child cannot be projected in the ultrasound examination. Merely because the child was born underweight is known as SFD (Small for Date). The OP contended that the doctor had explained the complainant through diagrams and medical literature showing the possibility of the child being mentally retarded, whereas the complainant did not follow the medical advice and rather started consulting some other persons. There is no material produced by the complainant to show any lapse or deficiency in service on the part of the OPs in either not diagnosing or prescribing medical treatment as is apparent from the aforesaid contentions. …..……….. The child was born with umbilical cord surrounding its neck. Though we have all the sympathy for the complainant but the aforesaid facts do not make out a case of medical negligence or any deficiency in service on the part of the
MEDILAW OP Hospital or doctors and they cannot be held liable for any lapse or negligence during or after delivery of the child. The complaint is dismissed being devoid of substance.
this could be done, the appellant’s wife herself delivered 1 month prematurely with only 1 hour of labor pains. ÂÂ
On birth, the infant was in respiratory distress because the umbilical cord was bound thrice round his neck and he had passed and swallowed meconium in the womb. He was immediately resuscitated, stabilized and put in intensive care and prescribed antibiotics and treated with other medication for mild jaundice and discharged thereafter in a stable and satisfactory condition.
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It was the appellant and his wife who failed to heed correct medical advice during subsequent follow-up visits by not agreeing to hospitalization of the baby and also not giving antibiotics for the prescribed period.
Hence, the present first appeal. ALLEGATIONS OF COMPLAINANT Appellant who was present in-person and Counsel for Respondents made oral submissions. ÂÂ
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Appellant reiterated that if proper tests including the TORCH test had been conducted, the type of viral infection from which both the mother and the fetus had been obviously infected would have been detected and the mother could have been given proper medication instead of only crocin and the baby could have been given the medical attention required in such cases at birth instead of only antibiotics and tonics. The certificate from AIIMS clearly indicated that the condition of the child, who unfortunately is no more, was because of the perinatal viral infection. If proper medication had indeed been given immediately in all possibility the retardation would have been checked at birth instead of increasing over the years. Appellant apprehended that there was every possibility that the mother was given certain medications which were contraindicated though on a specific query from us, he could not state what other medicines were given.
OBSERVATIONS OF NCDRC We have heard the appellant and the Counsel for respondent and have carefully gone through the evidence on record. ÂÂ
We note from the record that as observed by the State Commission due care was taken in the prenatal care of the appellant’s wife by Respondent No. 1 and necessary tests were conducted.
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Appellant’s contention that there was negligence in not conducting the TORCH test when the appellant’s wife contracted fever between 32-34 weeks of pregnancy is not borne out by the medical literature on the subject according to which a TORCH test is prescribed within first 12 weeks of pregnancy in case the mother is suffering from fever because this is the period when fetal malformation can occur due to certain infections (Reference: American Pregnancy Association and MCRCK, manual on high risk pregnancy risk factors).
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Admittedly, the appellant’s wife suffered from fever only a few weeks before the delivery and she was given paracetamol, which is not contraindicated.
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While it is a fact that the child was born with cerebral palsy and related problems, as per the medical literature, this could not have been detected in the womb or caused because of any medication or wrong treatment when the appellant’s wife had fever just prior to her delivery.
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Since the fetus was small for date, due care was taken and a few days after the birth when covert symptoms of cerebral palsy disease became apparent, appellant and his wife were immediately advised about the problem and also given a prognosis.
REJOINDER OF RESPONDENTS ÂÂ
Counsel for respondents on the other hand stated that both respondents are well-qualified doctors with specializations in Gynecology and Pediatrics, respectively.
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Respondent No. 1 took due care during the pregnancy and right in the beginning various tests including ultrasound were conducted which could have revealed some growth problem but not spastic tendency or cerebral palsy because spastic tendencies cannot be diagnosed in a fetus.
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The fever which occurred in the 32-34 weeks of the pregnancy in the mother cannot cause fetal malformation, which can occur if the mother contracts an infection in the first trimester i.e., 12 weeks of the pregnancy. Since an ultrasound had confirmed that the fetus was small for date, as per medical practice, respondent planned to induce labor but before
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MEDILAW OPINION OF NCDRC Appellant has not been able to prove through any credible evidence that there was medical negligence or deficiency on the part of the respondents or any action or omission on their part which resulted in or aggravated the congenital condition of the infant. On the other hand there is credible evidence that right through the prenatal period and after the birth due medical attention and proper treatment was given by both Respondents who are well-qualified specialists in their fields. Further, the certificate from AIIMS on which the appellant has relied was given some years later and only a question mark was put regarding the cause of the cerebral palsy being the
prenatal viral fever from which the appellant’s wife suffered and it was not a definite opinion on the same. ORDER OF NCDRC The State Commission has carefully considered all these aspects and has given a well-reasoned order concluding that the appellant has not been able to prove that this was a case of medical negligence or that there was any deficiency in service on the part of the respondents. We agree with these findings and therefore, uphold the order of the State Commission. The first appeal is dismissed with no order as to costs.
Reference
1. Case no. 490 of 2007; Order date 13.09.2012. ■■■■
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CONFERENCE PROCEEDINGS
54th Annual Conference of Indian Academy of Pediatrics (PEDICON 2017) BE ACADEMICALLY STRONG, HONEST AND HARD WORKING Dr Bakul Jayant Parekh, Hony Secy Central IAP What are your views on PEDICON 2017? PEDICON 2017 is one of the largest annual conferences in our history, which I observed. Every year, we have 7,000-7,500 delegates but I have heard that this time more than 10,000 delegates have registered. All of them have been accommodated so very nicely; the arrangements of PEDICON 2017 are very well made and well-structured. And I must congratulate the Organizing Secretary Dr Karunakara, along with the Organizing Chairperson, Dr Govindaraj and his team for putting in lots of efforts since last 1 year, for spending their valuable time, burning their midnight oil and putting their blood and sweat in the arrangements. Do you have any message for the upcoming pediatricians? The message I would like to give to the upcoming pediatricians is - Be academically strong, be sincere, honest and hard working in your practice; be available all the time when your patients need you. Try to counsel the patients much more than what we do usually and also, don’t compare yourself with other sectors like IT, business, etc., where a person starts earning early and has lots of huge packages available. But mind you, you have selected your profession, which is a noble profession which is service-oriented; your profession makes you stand next to God, people respect you and you are going to earn enough to live a luxurious life. So, don’t compare yourself with other professionals.
the Organizing Chairman will be Dr Vasant Khalatkar. I have known both of them for many years and they are the best organizers I have seen. What is your message for the pediatricians who are attending PEDICON 2017? Be very sincere in attending all your academic lectures and try to grab some “Take Home Messages”, which will be helpful in your day-to-day practice. Try to send messages in the Central IAP if you have any complaints or suggestions. These would be constructive suggestions for us in Central IAP to improve further and give you the best. TRANSDISCIPLINARY, INTERSECTORAL AND MULTICENTRIC RESEARCH STUDIES Dr Narendra K Arora, New Delhi Integrative Approach to Address Complex Challenges ÂÂ
Specifically tailored (disciplined-based) research questions provide essential knowledge, methods and tools but they are inadequate to address complex challenges.
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In the real world, challenges are not ‘disciplined’ and multiple factors across domains influence outcomes.
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Research questions should therefore be more challenge oriented and there is a need for integration of disciplinary knowledge across sectors.
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The 17 SDGs represent a global emphasis on integrative approach.
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Transdisciplinary approach means working with the same problem by transcending disciplinary boundaries, cross fertilizing assumptions, resolving conflicting viewpoints. The outcomes add to the body of knowledge and provide practical solutions leading to improved theories and models, newly invented methods and novel synergies of systems.
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INCLEN has carried out various studies in India with support from the Govt. of India and other stakeholders.
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The study “Social Determinants of Polio Eradication Program in High Risk Districts of India An
What can we expect in the next PEDICON? The next PEDICON is going to be in the “Orange City” of Nagpur, and my friends in Nagpur are so very keen to be the best host in the country and I am sure that those who are going to attend that conference are likely to enjoy the academic feast as well as the gastronomic feast. The Nagpur PEDICON is going to be headed by the patron Dr Uday Bodhankar, my very close friend. The Organizing Secretary will be Dr Jayant Upadhyay and
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CONFERENCE PROCEEDINGS INCLEN Study (2002)” made recommendations for social implementation, which included an effective primary health service to restore the community’s trust and confidence, explain “Why Polio Eradication Campaign”, involve Clergy from all religions, include all resistant/reluctant groups within communities and devise a predefined and proactive media and strategic communication approach to clarify doubts and misconceptions. ÂÂ
Between 2002 and 2005, the IndiaCLEN study assessed the injection practices in India to find out what options are available for India to improve rationale and safe use of injections.
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Acting on the findings of this study that almost 2/3rd injections were administered in an unsafe manner and 1/3rd carried the risk of transmitting blood born injections–the Health Minister made a statement in Parliament on July 21st 2004 regarding Injection Safety “The Government of India has decided to introduce Auto Disable (AD) syringes for administering injections under Universal Immunization Program (UIP).” And, the autodisabled syringes were introduced in the National Immunization Program in the year 2006.
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INCLEN Principles of Partnership: Nothing confidential (partners communicate among themselves), Network not “Networking” and Avoid changing/dropping partners. INCLEN partners all those who are willing to work together, previous experience not mandatory.
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Another study funded by INCLEN was regarding Public Health Approach to Screening and Diagnosis of Neuro-Developmental Disorders (NDDs) in 2-9 years old children in India (2005-2014). The expected outcome was the development of a national program to address the issues on NDDs. The overall prevalence of any NDD - 12.0% (Census 2011). The prevalence data from the study were conveyed to the Govt. of India and based on which, a nationwide program “Rashtriya Bal Swasthya Karyakram” (RBSK) was launched on 6th February, 2013 by the Govt.
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For the first time, guidelines for certification of Autism were launched by the Govt. on 26th April 2016, which said “INCLEN Diagnostic tool shall be used for identification of Autism cases in the Country”.
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Another study, which evaluated determinants of undernutrition in children and assessment
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of management at different level of healthcare (2010-2012) observed that determinants of nutrition are multifactorial. Social factors also contribute to undernutrition and not just poverty and food insecurity. A mother with less time to provide optimal care to her child was an important factor influencing undernutrition. It is an intersectoral problem, which needs coordinated action. ÂÂ
Towards a transdisciplinary approach: Living with tensions: Transdisciplinary research requires the management of diversity and “tangled agendas”. There is no right methodology, except being aware of tensions. Formation of team: Teams need to be big enough to be diverse but small enough to build relationships. Outputs: Negotiation is required at an early stage to ensure outputs satisfy all team members, as well as funders. Negotiation of the research approach: Develop methods of engaging all partners. Facilitators and stakeholder workshops can be key to ensuring good communication, managing expectations and ensuring equality among all participants. Knowledge creation: To avoid the pitfalls of a multidisciplinary or multistranded approach, transdisciplinary projects ensure integration of all aspects of the research. Allow time and space so that there is room to fail and the opportunity to learn from mistakes.
Constant engagement with partners – Do not get frustrated!!! “Always bear in mind that your own resolution to succeed is more important than any one thing.” –Abraham Lincoln CLIMATE CHANGE IMPACT ON RESPIRATORY ALLERGY Dr H Paramesh, Bengaluru ÂÂ
Climate change is a global phenomenon with rise in temperature, sea level and hydrologic extremes. By the end of the 21st century, the temperature is expected to increase 1.1-16.4°C.
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It is a public health hazard. Climate change exaggerates all the risks of environmental pollution.
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Extreme weather-related health effects include heat stress, CV failure, injuries. Others include air pollution (asthma, cardiovascular disease), allergies (respiratory allergies), vector-borne disease (malaria, dengue, chikungunya), waterborne disease (cholera, leptospirosis), psychosocial impacts on displaced populations (anxiety, PTSD, depression) and health impacts from conflicts (forced migration).
CONFERENCE PROCEEDINGS ÂÂ
Rapid urbanization, change in demography, air pollution from traffic are the major cause for increased prevalence of asthma (H Paramesh. Ind J Ped. 2002, 2006; H Paramesh. Int J Environ Health. 2008).
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Salbutamol nebulizer without oxygen can lead to VQ mismatch and worsen hypoxia.
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Aggressive treatment with IV Mg, SC adrenaline and aminophylline may be warranted in lifethreatening asthma.
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There is a window period where high flow nasal cannula and noninvasive ventilation can be tried in early phase.
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Avoid intubation, if possible. Use permissive hypercapnea and lung protective ventilator settings if ventilating.
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Traffic and power generation causing outdoor air pollution is the cause for exacerbation of preexisting asthma and contributes to new onset asthma as well (Guarneri, Balmes. Lancet. 2014).
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Climate change will be the defining issue for health system in the 21st century.
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Adaptation to climate change is essential in primary prevention of health issues.
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Climate change will widen the health equity gap within and between countries.
Do not assume that everything is alright; be vigilant.
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Every intervention should be followed by a rapid re-assessment and continuous monitoring.
LACTATION MANAGEMENT REVISITED: JAIPUR EXPERIENCE
DELIVERING PALLIATIVE CARE: CARE BEYOND CURE
Prof Dr S Sitaraman, Jaipur
Dr Veronique Dinand, New Delhi
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Nearly one-third mothers have lactation problems immediately after delivery.
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Milk secretion at the end of week is more than 500 mL; it would ensure successful lactation till 6 months.
Palliative care should be offered to all children with chronic illnesses from the time of diagnosis until cure or death.
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Comfort care should be provided from the beginning, alongside care with curative intent.
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Aim is to improve the quality-of-life of patients and their families facing serious life-limiting illness: Children suffering from HIV, chronic renal failure, cardiac failure, respiratory diseases, neurological and musculoskeletal disorders, cancer and hematological disorders, genetic conditions.
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Holistic approach: Prevention and relief of suffering from pain and other physical symptoms as well as psychological, social and spiritual distress.
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Multidisciplinary team including pediatrician, nurse, psychologist/counselor, social worker, physiotherapist/occupational therapist.
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Palliative care can be integrated into RBSK for early detection and intervention, through capacity building of healthcare workers.
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Education in palliative care: A distance learning 6 months Certificate Course in Pediatric Palliative Care will soon be offered to Pediatricians.
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Breastfeeding and skin-to-skin contact within the 1st hour is required for initiation of feed.
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Lactation counselors are the cadre of workers, who can ensure 100% breastfeeding in all set ups.
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These highly motivated (just graduates) counselors, who have been trained with appropriate counseling skills can bring about a dramatic change in rates of breastfeeding.
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We do not require milk banks everywhere; we require just lactation management centers with motivated lactation counselors.
ACUTE SEVERE ASTHMA - GUIDELINES Dr Ebor Jacob, Vellore ÂÂ
Recognize asthma correctly since “all that wheezes is not asthma”.
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Degree of wheezing does not always correlate with severity of the disease.
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Assess severity on arrival.
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Normal oxygen saturation does not rule out severity.
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Short-acting beta-agonists (SABA) + ipratropium with O2 flow and steroids form the first-line therapy.
ROLE OF PARENTS IN HOLISTIC DEVELOPMENT OF ADOLESCENCE Dr MN Venkiteswaran, President, IAP, Kerala State ÂÂ
Holistic development focuses on addressing all of the needs of a child’s life: Emotional, physical, relational, intellectual, creative and spiritual.
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CONFERENCE PROCEEDINGS ÂÂ
The family ensures and provides physical, economic, cultural and moral support to a child.
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Parental involvement is a key ingredient in fostering adolescents’ success.
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Understanding your child is one of the most important things that you should learn as a parent.
5As of pediatric obesity management: Ask, Assess, Advise, Agree and Assist
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Focus on healthy eating principles rather than diet charts and weight loss; include physical activity in daily routine and structured play; reduce sedentary time.
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Family-centered behavioral modification pertaining to food habits, food faddism; healthy lifestyle education in school.
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Pharmacotherapy and bariatric surgery is generally not recommended.
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Many outside influences distract our adolescents and complicate our efforts.
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Young people who feel their parents’ love are less likely to get into trouble.
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Teens look for care, acceptance, respect and trust.
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Good parents would like to be friends with their kids, but they choose to be a parent first. Provide unconditional love and help them to feel safe.
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Through supporting, monitoring and encouraging, we can develop a civilized generation.
imposed by obese state and not hypothyroidism. Such mild elevation of TSH should not be treated with thyroxine.
VIOLENCE AGAINST THE GIRL CHILD: WHAT DO WE KNOW ABOUT THE EFFECTS ON HEALTH AND WELL-BEING?
OBESITY AND METABOLIC SYNDROME Dr Vaman Khadilkar, Pune ÂÂ
Obesity in children and adolescents is on the rise. Prevalence of childhood obesity in urban India is 5-9% and that of overweight is 15-25%.
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Obesity is a lifestyle disease; primary hormonal problems causing obesity in adolescents are rare.
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Children with primary hormonal obesity are short and fat. Secondary hormonal problems such as insulin resistance and PCOS are more common.
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Metabolic syndrome and T2DM are now seen at a younger and younger age!
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Investigations for obesity include overnight fasting lipid profile, liver enzymes and abdominal USG for NAFLD. Fasting glucose and insulin ratio in adolescents with suspected metabolic syndrome and/or T2DM, OGTT, A1c (not yet accepted by WHO as a single diagnostic test of diabetes in children though ADA favors it as a screening test).
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Mild elevations of TSH and T3 are common in obese children and adolescents and are an effect of leptin drive and peripheral thyroid resistance
Dr Shanti Raman, Sydney ÂÂ
Violence against children is both a human-rights violation and a public-health problem, and incurs huge costs for both individuals and society.
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The burden and long-lasting consequences of violence against children are considerable, both to the children themselves and to society at large; this burden is significantly heightened for girls and women in India.
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Specific consequences of violence against the girl child include: missing girls due to infanticide/ feticide; selective bias in access to health, education, employment, opportunity; child marriage; malnutrition, stunting and gender-based violence.
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Pediatricians should be actively engaged in advocacy to prevent violence against children and violence against the girl child in particular.
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The first step is education. All pediatricians should be able to medically assess and intervene in child maltreatment.
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Positive discrimination towards the girl child is another step in preventing violence against them.
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CONFERENCE PROCEEDINGS
7th World Congress of Diabetes (DiabetesIndia 2017) “J-shaped anchor lock domain”, which provides potent and long duration of action.
OPTIMIZING OPPORTUNITIES WITH PREMIX INSULIN CO-FORMULATION Dr Shashank Joshi, Mumbai ÂÂ
Insulin offers maximum efficacy in terms of glycemic control and early insulin therapy can help reduce long-term complications.
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IDegAsp is a novel insulin co-formulation with distinct basal and prandial glucose lowering effects. IDegAsp administered OD has been found to be superior to insulin glargine in improving glycemic control and postprandial glucose excursions, without compromising FPG control or safety.
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It may delay progression of type 2 diabetes by the virtue of its β-cell preserving properties.
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It is effective in tackling short-term glucose fluctuation and related oxidative stress.
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It improves endothelial dysfunction and arteriosclerosis. It is safe in cardiac and renal comorbid patients.
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It is an appropriate add-on to metformin early in therapy to delay exhaustion of pancreatic islet function.
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Body weight and insulin dose are both significantly lower with IDegAsp BID when compared to basalbolus therapy IDeg or IAsp.
TECHNOLOGIES IN DIABETES MANAGEMENT: FUTURE PERSPECTIVE
ÂÂ
The rates of confirmed and nocturnal confirmed hypoglycemia are numerically lower with IDegAsp BID compared with IDeg OD + IAsp.
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Technologies and advances in diabetes have improved the management of diabetes to a great extent. Ambulatory glucose monitoring (AGP) has made monitoring of diabetes almost painless. AGP gives 14 days data of glucose level in a person with diabetes and also a 24-hour curve, which is very useful in identifying hypoglycemic episodes. AGP will help in educating the patient regarding monitoring body glucose level as well as fine tuning the insulin dose.
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Electronic medical record (EMR) combined with E-consult, point of care meters for blood glucose estimation, HbA1c, have made distant management of diabetes cost-effective and convenient to both the clinician as well as the patient.
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iPort - An insulin injecting port has made insulin administration a painless procedure.
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Insulin pump with a sensor, which has a crosstalk with the pump, has made artificial pancreas a reality.
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Mobile based apps for diabetes are available for distant consultation, monitoring blood glucose, ECG, heart rate, oxygen level in blood, monitoring diet, exercise, calories spent as well as an educational tool to know more about diabetes.
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Near infrared technology has made noninvasive glucose monitoring of blood a reality through a
Dr KM Prasannakumar, Bengaluru
BETA-CELL DEATH: FACT OR FICTION? Dr Krishna G Seshadri, Chennai ÂÂ
It all starts with fat cell expansion, after which fat cells are no longer able to hold extra fat, which eventually leads to increased intrahepatic and pancreatic lipids.
ÂÂ
Pancreatic b-cell mass does not change in diabetes; cells are present but insulin content comes down. Moreover, b cells are not lost but they are dedifferentiated into a cells. Therefore, in diabetes, predominance of a cells occurs.
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The whole process of differentiation of pancreatic cells into endocrine cells like a, b, δ, etc. is controlled by FOXO1 protein/gene. FOXO1 migrates inside the nucleus and in drastic conditions, suspends the amount of insulin production or converts pancreatic b cells into a cells.
DPP-4 INHIBITORS IN MANAGEMENT OF TYPE 2 DIABETES: FOCUS ON TENELIGLIPTIN Dr Anand Moses, Chennai ÂÂ
Teneligliptin, a third-generation gliptin, offers unique pharmacodynamic advantage with unique
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CONFERENCE PROCEEDINGS watch-like wearable instrument which measures heart rate, glucose, SPO2 frequently.
ÂÂ
It is known that hypoadiponectinemia (reduced level of adiponectin) increases the diabetes pandemic. It is observed that glimepiride corrects the condition of hypoadiponectinemia and reduces the TNF-a activity and hence helps to manage diabetes mellitus.
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No concrete evidence supports that glimepiride is associated with severe hypoglycemia. It is important to note that in diabetes patients, the pancreatic b cells are not destroyed by apoptosis; rather they are de-differentiated into glucagon producing a cells.
NEXT GENERATION OF Β-CELL REPLACEMENT IN DIABETES Dr Rajeev Chawla, New Delhi ÂÂ
T2DM is thought to arise from a combination of impaired β-cell function and reduced β-cell mass. Reductions in β-cell mass can begin early in T2DM, even before the IGT stage. Multiple mechanisms are responsible for β-cell failure.
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Obese individuals with IFG have 40% less β-cell mass and volume than nondiabetic individual. Obese individuals with T2DM have >60% less β-cell mass and volume than nondiabetic individuals.
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Individuals transitioning from prediabetes to T2DM have: β-cell dys-/hypofunction; lipotoxicity; ER/oxidative stress; inflammation; impaired incretin effect.
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Induction of inflammatory cytokines and metabolic stress play a role in β-cell apoptosis. Aggregates of cytotoxic islet amyloid polypeptide (IAPP) have a role in β-cell dysfunction.
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Preservation of β-cell function in T2DM: Therapies aim to decrease β-cell workload or induce β-cell rest; early short-term insulin therapy can improve underlying β-cell pathology. Oral antidiabetic agents demonstrate positive effects on β-cell function in patients with T2DM. Imeglimin is the first in the class of drugs called the “glimins” and, more specifically, is a tetrahydrotriazine compound. Imeglimin improved β-cell function after 1 week of treatment. Therapies to restore β-cell mass are in development and include stem-cell replacement and regeneration techniques.
CHALLENGING THE MYTHS ABOUT SUS: WHAT’S THE EVIDENCE? Dr Awadesh Kumar Singh, Kolkata ÂÂ
Sulfonylureas (SUs) have got robust glucose reduction capability.
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SUs are effective, cheap and time-tested medication for diabetes management. They show no significant CV events.
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Glimepiride increases insulin sensitivity and thus demonstrates extra pancreatic activity.
Indian Journal of Clinical Practice, Vol. 28, No. 3, August 2017
NONALCOHOLIC FATTY LIVER: RELATIONSHIP TO DIABETES AND MANAGEMENT Dr Anoop Misra, New Delhi ÂÂ
NAFLD is a chronic condition characterized by hepatic fat accumulation (in the absence of ethanol abuse and other identifiable causes), associated with insulin resistance, hyperglycemia, and CVD, identified by imaging/histology.
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NAFL is the presence of fatty liver without hepatocellular injury. NASH is the presence of hepatic steatosis and inflammation with hepatocyte injury with/without fibrosis.
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NAFLD is prevalent in Asian Indians, and may be more severe than in other areas. These adverse features are contributed by excess body fat, SC and IA fat, excess FFAs and insulin resistance.
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NAFLD is central to development of diabetes. Presence of moderately large fatty liver predicts diabetes.
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Lifestyle management including diet and exercise should be more aggressive; would help in prevention of diabetes.
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Medical therapy and bariatric surgery need to be judiciously applied.
EVOLUTION OF INSULIN: APPLYING FUNDAMENTALS OF INSULIN PHYSIOLOGY TO BUILD A BETTER INSULIN Prof Samar Banerjee, Kolkata ÂÂ
Banting and Best extracted insulin from dog pancreas and proved that it can control symptoms of diabetes in dogs in 1921. Since then, many improvements have been done.
ÂÂ
The existing newer insulin formulations have helped us to reach closer to physiology.
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Currently available insulin preparations are administered subcutaneously. Subcutaneous
CONFERENCE PROCEEDINGS insulin administration does not produce plasma profiles that mimic normal physiology. Attainment of ‘near-normoglycemia’ is the aim of managing diabetes mellitus. ÂÂ
New formulations which may be available in the near future will help improve patient adherence and outcomes.
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Smart insulin acts only when blood glucose goes high and stops working when blood glucose is normal.
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Ultrafast short-acting and basal insulins of higher concentration and small volume are also promising.
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Once a week basal insulin and noninjectable insulins, like inhalational insulin with technosphere technology and oral insulins are also under trial.
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Final target is to have insulin not producing hypoglycemia, weight gain, exogenous insulin resistance, to be administered by noninjectable route.
ESTABLISHING DIABETIC FOOT CLINIC Dr Hardik Chandarana, Ahmedabad Diabetic foot disease is one of the major causes of morbidity and mortality in people with diabetes. It contributes to the majority of diabetes-related hospitalizations and, therefore, accounts for much of the cost of diabetes to health budgets. Diabetes foot disease is the most common cause of nontraumatic lower-limb amputation globally. However, most foot problems are preventable through early detection of the problem and prompt treatment by a skilled multidisciplinary healthcare team. People working in foot care should be encouraged to develop a special interest group in this very important area to share knowledge and best practices. SULFONYLUREAS: CV SAFETY Dr Dheeraj Kapoor, Gurugram The American Diabetes Association (ADA) guidelines recommend initial metformin therapy for most newly diagnosed T2DM and add a second oral drug or a GLP-1 receptor agonist, if A1c targets are not achieved over 3 months. The association between sulfonylurea (SU) treatment and the risk of incident CVD is much debated. The approved package labels for all SUs bear a warning for increased CV risk. As T2DM already increases CV risk, it would be prudent for clinicians to avoid the use of drugs that may add to risk of precipitating an event.
The University Group Diabetes Program (UGDP) was the first study to suggest a positive association between the use of a first-generation SU and risk of CVD. SU receptors are also present in the myocardial tissue and similar action in cardiac tissue may lead to inhibition of myocardial preconditioning. In UKPDS, patients given a combination of metformin and SU had an increased risk of diabetes-related and all-cause mortality. SUinduced hypoglycemia may also contribute to increased CVD risk. It increases myocardial oxygen consumption by producing a sympathoadrenal activation. A reported meta-analysis that compared with other oral diabetes medications, SU use was associated with a significantly increased risk of CV-related deaths and hospitalizations. Synthesis of available evidence has shown that SU use may be associated with increased CV events, despite the moderate-to-high heterogeneity among included studies. These results warrant consideration in clinical practice, when other treatment options may be available. However, since SU are both effective and cheap, they remain one of the most commonly prescribed add-on therapies. INTENSIVE INSULIN THERAPY AT THE DIAGNOSIS OF DIABETES: FACT OR FICTION? Dr Hemant Mankad, Ahmedabad Long-term glycemic control reduces the risk of CVD if early and sustained glycemic control could be started before atherosclerosis is established. Rationale for early insulin use - b-cell dysfunction begins before onset of hyperglycemia. Therefore, insulin given at time of diagnosis is not too early. In line with guidelines, basal insulin can be timely introduced aiming at target HbA1c. The TULIP trial has shown the effectiveness of timely implementation of an insulin glargine-based management. ORIGIN trial showed a reduction in macrovascular events based on an early insulin replacement therapy strategy. In Asia, Weng et al have shown that an early intervention with insulin therapy not only improves glycemic control, but also has a positive effect on β-cell function. LIPODYSTROPHY Dr Sudha Vidyasagar, Manipal ÂÂ
Lipodystrophies are classified as inherited and acquired. They are further divided into general and partial. They occur due to disorders of fat metabolism and distribution; patients have low leptin levels.
Indian Journal of Clinical Practice, Vol. 28, No. 3, August 2017
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CONFERENCE PROCEEDINGS ÂÂ
Metabolic abnormalities such as insulin resistance, diabetes and increased TG are common. Metabolic syndrome, obesity are close differentials.
ÂÂ
HIV and HAART are important causes of acquired lipodystrophy.
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Insulin injections can cause local atrophy of hypertrophy of fat. This can lead to erratic absorption and poor control of diabetes. For other lipodystrohies, leptin is the treatment of choice.
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Recognition of the link to diabetes may fuel further research into underlying mechanisms and therapeutic targets.
DIABETES AND CANCER: THE LINK
by few committed individuals/Prof MMS Ahuja: Implementation of systematic patient health education and self-care training programs at clinic/ hospital; enrichment of medical education (UG/ PG level), CME of physicians at all levels; limited public philanthropy, free insulin and medical care via few grass root organizations (supported also by industry); increasing number of physicians and other health professionals - manpower and skills development; significant drop in cost of insulin; implementation of certified insulin pump therapy programs and CGM programs; Government focus for diabetes care. ÂÂ
Insulin love and care: Beside physiological substitution of insulin, psychosocial care is probably the most important part of the management of diabetes in children and adolescents.
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Spiritual poverty: In a reverse situation, a subset of affluent - affordable (“rich”) group of children, also face numerous challenges and difficulties with their type 1 diabetes. These challenges are predominantly psychosocial, and these youngsters also need consistent, life-long and genuine love and care, from all concerned - family, society and the diabetes care team.
Dr Sandeep Tak, Jodhpur Having diabetes, obesity or signs of insulin resistance may lead to an increased risk of certain cancers. The connection is strongest among certain types of cancers, including liver, pancreatic, kidney and colorectal. In diabetics, cancer behaves more aggressively leading to more deaths than nondiabetics and there is increased risk of recurrence. There is also concern about use of various antidiabetic drugs, insulin, and cancer development: There was concern about insulin use, particularly glargine and cancer but, it was put to rest in ORIGIN trial. On the positive side, several studies and meta-analysis suggest that metformin reduces the risk and progression of malignancy as well as improves survival in treated subjects. Treating physician must decide if remote yet plausible cancer risks weigh more heavily than suboptimal glycemic control and a higher likelihood of diabetes related complications in patients. Counseling on lifestyle changes and screening for cancer should be a part of regular preventive care in people with diabetes and/or obesity. CHILDHOOD AND YOUTH-ONSET DIABETES IN INDIA: PROFILE, CHALLENGES, PROGRESS AND FUTURE? Dr SS Srikanta, Bengaluru ÂÂ
Since the last 50 years, major progressive steps in diagnosis, medical care and longevity of children in India have been recorded because of: Global medical and technological advances. Dedicated, creative and socially relevant translational medicine and healthcare delivery programs, led
EARLY INTERVENTIONS FOR MAXIMIZING BENEFITS Dr Sanjay Kalra, Karnal DiabetesIndia endorses the philosophy and aims of the ‘The Berlin Declaration’, a global movement for local policy change to drive early action in type 2 diabetes. Early action is required in four areas, viz; prevention, early detection, early control and early access to the right interventions for halting the type 2 diabetes epidemic. Government leadership, support from diabetes care professionals, public involvement and multi-sectorial public-private partnerships are required to ensure early action in type 2 diabetes. The Indian government has taken proactive steps and formed effective policies for diabetes care. A 10% per annum rise in the number of people who are tested for glycemic control and complications, and who achieve their goals, is suggested by DiabetesIndia. Adequate early diabetes prevention, detection and control cannot be achieved without the help of trained and qualified manpower. Early access can be facilitated by training at least 10% healthcare professionals, at primary, secondary and tertiary levels, every year.
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AROUND THE GLOBE
News and Views 85 Million People Treated for Trachoma Through Expanded Access to Medicine New data released by the World Health Organization (WHO) show a remarkable 63% increase in the number of people treated with an antibiotic for trachoma during the period 2014-2016, considerably improving prospects for the global elimination of the disease. The surge is mainly due to an expanded access to donated azithromycin. Alongside the 63% increase in antibiotic treatments, the period 2014-2016 saw a steep rise in the number of people with advanced trachoma receiving operations to prevent further loss of sight - from 1,39,441 in 2014 to 2,60,759 in 2016, representing an 87% increase. WHO maintains updated information on its Global Health Observatory which is used by national trachoma programs to target delivery of the WHO-recommended SAFE Strategy … (WHO, July 13, 2017).
US FDA Approves Guselkumab for Plaque Psoriasis The US Food and Drug Administration (FDA) has approved guselkumab for adults with moderate-tosevere plaque psoriasis who are candidates for systemic therapy or phototherapy to be given as a 100-mg subcutaneous injection every 8 weeks, following two starter doses at Week 0 and Week 4. Guselkumab is the first and only approved biologic agent that selectively blocks interleukin-23.
Alendronate Reduces Fracture Risk in Older Patients on Steroids
traditional CVD risk factors. The study was presented July 8, 2017 at the Society of Cardiovascular Computed Tomography (SCCT) 2017 Annual Scientific Meeting in Washington, DC.
Children’s Visual Engagement is Heritable and Altered in Autism How children visually engage with others in social situations is a heritable behavior that is altered in children with autism, according to a study published July 12, 2017 in the journal Nature. Identical twins had synchronized visual patterns, compared to nonidentical twins and nonsibling pairs. Identical twins tended to shift their eyes at the same times and in the same direction. They also were more likely to look at the subject’s eyes or mouth at the same moments.
Smartphones Impair Cognitive Capacity Results from two experiments published online April 3, 2017 in the Journal of the Association for Consumer Research indicate that even when people avoid the temptation to check their phones the mere presence of these devices reduces available cognitive capacity. This effect is highest in those who have the maximum dependence on smartphones.
Perineural Invasion Increases Risk of Local Recurrence in Cutaneous Squamous Cell Carcinoma
According to a retrospective cohort study of older patients on prednisolone published in the July 11, 2017 issue of the Journal of the American Medical Association, additional treatment with alendronate significantly reduces the risk of hip fracture.
Patients with cutaneous squamous cell carcinoma (CSCC) and perineural invasion (PNI), identified clinically or radiologically, are at a higher risk of local recurrence (37%) and disease-specific death (27%). The study reported online July 5, 2017 in JAMA Dermatology suggests increased long-term surveillance for patients with clinical perineural invasion.
CAC Score Along with Risk Factors Increase Allcause Mortality Risk
Private Hospitals should Display their Cesarean Delivery Rates, Says Health Ministry
Results of a large registry study of asymptomatic patients who had a physician-requested coronary artery calcium (CAC) CT scan show increased risk of all-cause mortality, especially cardiovascular disease (CVD) mortality, with a high CAC score. Patients who had CAC >400 had a 1.8-fold to 3.2-fold increased risk of all-cause death and a 3.1 to 5.1-fold increased risk of CVD death. The risk increased with the number of five
In response to the letter of Minister of Women and Child Development expressing concern about the high cesarean rates in the country, the Union Minister of Health and Family Welfare, Shri JP Nadda has directed all the private hospitals empanelled under CGHS to prominently display the data of deliveries through C-section vis-à-vis normal deliveries in the hospital, at the reception area.
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AROUND THE GLOBE A report titled “Deciphering the Determination and Impacts of Rising Rate of C-sections and offering Potential Solutions” has been disseminated to all State Governments and UT Administrations to effectively get them to provide C-sections only to those women who actually require it. Federation of Obstetric and Gynecological Societies of India (FOGSI) has also been sounded off about the harmful effects of unwarranted C-sections … (Press Information Bureau, Ministry of Women and Child Development, July 14, 2017)
Pericarditis may be a Sign of Occult Cancer, Says Study New data reported online June 29, 2017 in the journal Circulation suggest that pericarditis may be a marker of occult cancer - lung, kidney and bladder cancer, lymphoma, leukemia and unspecified metastatic cancer and predicts increased mortality following a cancer diagnosis.
Closed Incision Negative Pressure Therapy may Reduce Post-colorectal SSIs According to findings presented June 11 at the 2017 American Society of Colon and Rectal Surgeons Annual Scientific Meeting in Seattle, Washington, closed incision negative pressure therapy (CINPT) for wounds may help prevent postoperative surgical site infection (SSI) after colorectal surgery, especially in high risk conditions such as dirty wound, obesity, diabetes, immunosuppression.
Boxers may have Signs of Long-term Brain Injury in Blood Boxers and mixed martial arts fighters may have markers of long-term brain injury in their blood, according to a study presented July 13, 2017 at the American Academy of Neurology’s Sports Concussion Conference, which concluded in Jacksonville, Florida. The active professional fighters had higher levels of neurofilament light chain and tau. Neurofilament light has been suggested as a more sensitive marker for acute brain trauma.
Biopsy Not a Requisite to Confirm Diagnosis of Celiac Disease in Children Tissue transglutaminase levels 10 times the upper limit of normal, a positive result from the endomysium antibody testing (EMA) tests in a second blood sample, and the presence of at least one symptom can reliably diagnose celiac disease in children without the need for a biopsy, A study reported online June 15, 2017 in the journal Gastroenterology.
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FDA Approves Blinatumomab for Acute Lymphoblastic Leukemia In an upgrade from the accelerated approval status, the US Food and Drug Administration (FDA) has granted full approval to blinatumomab (Blincyto, Amgen) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in both adults and children.
Avoid Eating Fried Potatoes to Reduces Mortality Risk Participants in a study, reported in the July 2017 issue of the American Journal of Clinical Nutrition, who consumed fried potatoes 2-3 times in a week and 3 or more times in a week were at an increased risk of mortality. While, no association with an increased mortality risk was noted with consumption of unfried potatoes.
Eye Microbiome Trains Immune Cells to Fend Off Pathogens The ocular surface has been thought to be sterile for years. However, a new research conducted in mice and published June 27, 2017 in the journal Immunity has demonstrated the existence of a resident ocular microbiome that trains the developing immune system to fend off pathogens.
Greater Emphasis on Preventing and Treating Heart Disease in Women Needed Women and physicians do not put enough emphasis on cardiovascular disease in women, and a social stigma regarding body weight may be a primary barrier to these important discussions, according to research published June 22, 2017 in the Journal of the American College of Cardiology.
Measles Continues to Spread and Take Lives in Europe Ongoing measles outbreaks in the WHO European Region have caused 35 deaths in the past 12 months. The most recent fatality was a 6-year-old boy in Italy, where over 3,300 measles cases and 2 deaths have occurred since June 2016. Several other countries have also reported outbreaks; according to national public health authorities, these have caused 31 deaths in Romania, 1 death in Germany and another in Portugal. “Every death or disability caused by this vaccine-preventable disease is an unacceptable tragedy,” says Dr Zsuzsanna Jakab, WHO Regional Director for Europe. “We are very concerned that although a safe, effective and affordable vaccine is available, measles remains a leading cause
AROUND THE GLOBE of death among children worldwide, and unfortunately Europe is not spared. Working closely with health authorities in all European affected countries is our priority to control the outbreaks and maintain high vaccination coverage for all sections of the population.” (WHO Europe, July 11, 2017).
Fecal Immunochemical Testing is the First Tier Screening Test for Colorectal Cancer In its latest recommendations, the US Multi-Society Task Force (MSTF) on Colorectal Cancer (CRC) Screening has confirmed that people at average risk should be screened beginning at age 50, and recommends colonoscopy and fecal immunochemical testing (FIT) as the “first tier” screening tests for this group. “Colorectal Cancer Screening: Recommendations for physicians and patients from the US MultiSociety Task Force on Colorectal Cancer” was published online June 6, 2017 simultaneously in the American Journal of Gastroenterology, Gastroenterology, and GIE: Gastrointestinal Endoscopy.
Laser Speckle Contrast Imaging can Tract Gastric Microcirculation During Surgery Gastric microcirculation can be followed in real-time by laser speckle contrast imaging during esophagectomy. According to a study reported June 29, 2017 online in the Journal of the American College of Surgeons, changes in flow in the stomach are related more to surgery than to thoracic epidural anesthesia or the vasopressor support.
New Data Provide More Evidence of Renoprotective Effect of Empagliflozin New data from the EMPA-REG-OUTCOME study further support short-term and long-term benefits of empagliflozin on urinary albumin excretion, irrespective of patients’ albuminuria status at baseline, in patients with type 2 diabetes and established cardiovascular disease. These findings were published online June 27, 2017 in the Lancet Diabetes and Endocrinology.
Prostatectomy Offers No Added Advantage vs Observation in Prostate Cancer Patients Prostatectomy was not associated with significantly lower all-cause or prostate-cancer mortality than observation, according to analysis of two decades of follow-up data among men with localized prostate cancer. While surgery was associated with a higher frequency of adverse events vs. observation, it had a lower frequency of treatment for disease progression, mostly for asymptomatic, local or biochemical
progression. The study was reported July 13, 2017 in the New England Journal of Medicine.
WHO Estimates Cost of Reaching Global Health Targets by 2030 The Sustainable Development Goal (SDG) Health Price Tag, published in The Lancet Global Health, estimates the costs and benefits of progressively expanding health services in order to reach 16 SDG health targets in 67 low- and middle-income countries that account for 75% of the world’s population. The analysis shows that investments to expand services towards universal health coverage and the other SDG health targets could prevent 97 million premature deaths globally between now and 2030, and add as much as 8.4 years of life expectancy in some countries. While most countries can afford the investments needed, the poorest nations will need assistance to reach the targets. The SDG Health Price Tag models two scenarios: an “ambitious” scenario in which investments are sufficient for countries to attain the health targets in the SDGs by 2030, and a “progress” scenario in which countries get two-thirds or more of the way to the targets… (WHO, July 17, 2017)
FDA Approves New Treatment to Reduce the Risk of Breast Cancer Recurrence The US Food and Drug Administration has approved Nerlynx (neratinib) for the extended adjuvant treatment of early-stage, HER2-positive breast cancer. It is indicated for adult patients who have been previously treated with a regimen that includes the drug trastuzumab.
Long Working Hours are a Risk Factor for Newonset Atrial Fibrillation Results of a study reported July 13, 2017 in the European Heart Journal show that individuals who worked long hours (≥55 per week) were more likely to develop atrial fibrillation than those working standard hours (35-40 h/week).
Inflammatory Dietary Pattern Linked to Impaired Cognition A cross-sectional study presented July 17, 2017 at the Alzheimer’s Association International Conference (AAIC) 2017 in London, UK has found an association between inflammatory dietary pattern and cognitive function. Those who consumed less omega-3, less calcium, vitamin E, vitamin D and vitamin B5 and B2 had more inflammatory biomarkers.
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AROUND THE GLOBE Post-pregnancy HT Risk is High in Women with Hypertensive Pregnancy Disorders Compared to normotensive pregnant women, women with history of hypertensive disorders during pregnancy had a 12-fold to up to 25-fold higher risk of developing hypertension in the 10 years following their first pregnancy, says a study reported in the BMJ, published July 12, 2017.
Study Suggests Eye Exam for all Infants Potentially Exposed to Maternal Zika Infection New data published online July 17, 2017 in JAMA Pediatrics suggest that all infants who have been potentially exposed to maternal Zika virus at any time during pregnancy should be examined for eye abnormalities, whether CNS abnormalities are present or not, as these may be only initial finding in congenital Zika virus infection.
Not All Plant-based Diets are Created Equal, Says Study Plant-based diets are recommended to reduce the risk of heart disease. But, some plant-based diets are associated with a higher risk of heart disease, according to a study published July 17, 2017 in the Journal of the American College of Cardiology. Healthy plant foods (rich in whole grains, fruits, vegetables) were associated with lower risk, whereas less healthy plant foods (sweetened beverages, refined grains, potatoes and sweets) and animal foods were associated with higher risk.
World Medical Association Issues Urgent Plea to Venezuelan Government The World Medical Association has urged the Venezuelan Government to take immediate action to resolve the country’s serious health crisis, which it says has led to increased morbidity, mortality and malnutrition among infants. Venezuelan doctors have warned that a lack of medical supplies and basic food, plus the abandonment of prevention and treatment programs for vector control, have resulted in an increase in controllable diseases. Now the WMA has stepped up its support for the Venezuelan Medical Federation by calling on the Venezuelan Government to change Government policy and invest in health to prevent the situation from worsening and inflicting permanent damage on the country. WMA President, Dr Ketan Desai, has written to the President of Venuezuala Nicolás Maduro emphasizing the immediacy of the situation. “Urgent action is desperately needed because of the scarcity of trained
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medical personnel. Dedicated physicians are working under appalling conditions, with low salaries and in insecure hospitals. Many are sadly leaving the country. This cannot be allowed to continue. Without a healthy population, Venezuela will find it difficult to develop and grow. The country’s health service and its suffering population deserve better from the Government”… (World Medical Association, July 18, 2017).
First Pediatric Successful Double Hand Transplant The report of the world’s first successful double hand and forearm transplant in an 8-year-old boy has been reported July 18, 2017 in The Lancet Child & Adolescent Health. The child had developed staphylococcal sepsis with systemic ischemic injury when he was 2 years old and he then underwent quadrimembral amputation and developed kidney failure, for which he received a livingrelated kidney transplant from his mother at age 4. The authors write “As of 18 months after transplantation surgery he is able to write and feed, toilet and dress himself more independently and efficiently than he could do before transplantation”.
USPSTF Recommends Against Screening for Ovarian Cancer in Asymptomatic Women The US Preventive Services Task Force (USPSTF) Draft Recommendation Statement has recommended against screening for ovarian cancer in asymptomatic women. The draft recommendation statement and draft evidence review are available for review and public comment from July 18, 2017 through August 14, 2017 at the USPSTF website.
A New Therapeutic Option for Hepatitis C The US Food and Drug Administration has approved Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis. Vosevi is a fixed-dose, combination tablet of three drugs - sofosbuvir, velpatasvir and voxilaprevir. It is the first treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A.
Childhood Asthma may Lead to Thickening of Left Ventricle in Adulthood Young adults with a history of asthma are at a greater risk of thickening of the left ventricle (LV), which can cause shortness of breath, chest pain, fainting and eventually lead to heart failure, according to research published online June 26, 2017 in JACC: Heart Failure.
AROUND THE GLOBE During the 10 years of follow-up, participants with a history of asthma had a higher adjusted mean LV mass and LV mass index vs. those without asthma.
Early-onset of Natural Menopause is a Risk Factor for Type 2 Diabetes Women with premature, early and normal menopause were at a higher risk of developing type 2 diabetes compared to those with late menopause, according to a study of postmenopausal women free of type 2 diabetes at baseline reported in the journal Diabetologia, online July 18, 2017.
Study Shows No Beneficial Effect of Artificial Sweeteners on Weight Management There is no clear evidence from randomized controlled trials (RCTs) to support the intended benefits of nonnutritive sweeteners for weight management, according to a systematic review and meta-analysis of RCTs and prospective cohort studies published in CMAJ, online July 17, 2017. While observational data in the study show association of increased body mass index (BMI) and cardiometabolic risk with routine use of nonnutritive sweeteners.
Postoperative Stereotactic Radiosurgery for Brain Metastases Reduces Local Recurrences A single-center, phase III trial evaluating postoperative stereotactic radiosurgery vs. observation for completely resected brain metastases found that the local recurrence rate was twice as high with observation alone (48%) vs. stereotactic radiosurgery (24%). At 1 year, more patients (72%) in the stereotactic radiosurgery group were free from local recurrence compared to 43% in the observation group. The study was published online July 4, 2017 in The Lancet Oncology.
ICMR Invites Comments/Suggestions on Draft National Guidelines for Stem Cell Research, 2017 The Indian Council of Medical Research (ICMR) has invited comments and suggestions on draft National Guidelines for Stem Cell Research, 2017. The draft document had been placed in public domain for comments or suggestions from all and could be
downloaded from ICMR website. The last date for sending in comments was 31st July, 2017.
One in 10 Infants Worldwide did not Receive any Vaccinations in 2016 Worldwide, 12.9 million infants, nearly 1 in 10, did not receive any vaccinations in 2016, according to the most recent WHO and UNICEF immunization estimates. This means, critically, that these infants missed the first dose of diphtheria-tetanus-pertussis (DTP)-containing vaccine, putting them at serious risk of these potentially fatal diseases. Additionally, an estimated 6.6 million infants who did receive their first dose of DTP-containing vaccine did not complete the full, three dose DTP immunization series (DTP3) in 2016. Since 2010, the percentage of children who received their full course of routine immunizations has stalled at 86% (116.5 million infants), with no significant changes in any countries or regions during the past year. This falls short of the global immunization coverage target of 90%... (UNICEF/ WHO, July 17, 2017).
Study Reports Poor Stethoscope Hygiene A study published in the July 2017 issue of the American Journal of Infection Control has reported a zero percent rate for stethoscope hygiene. It also found that standard provider education, reminder flyers, and provision of cleaning supplies at the start of clinical rotations for house staff, medical students and attending physicians are insufficient to improve stethoscope hygiene rates. Hand hygiene rates did not change significantly with rates between 58% and 63% while stethoscope hygiene remained at zero.
Bleeding Complications Post-TAVR Indicate Poor Prognosis Among patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), accesssite and non–access-site bleeding were independently associated with an increased risk for mortality, with the greatest risk related to non–access-site bleeding during long-term follow-up, says a study reported in the July 24 issue of JACC: Cardiovascular Interventions.
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INSPIRATIONAL STORY
Story of Appreciation
O
ne young academically excellent person went to apply for a managerial position in a big company. He passed the first interview; the director did the last interview, made the last decision. The director discovered from the CV that the youth’s academic achievements were excellent all the way, from the secondary school until the postgraduate research, never had a year when he did not score good grades. The director asked, “Did you obtain any scholarships in school?” the youth answered “None.” The director asked, “Was it your father who paid for your school fees?” The youth answered, “My father passed away when I was one year old, it was my mother who paid for my school fees.” The director asked, “Where did your mother work?” The youth answered, “My mother worked as clothes cleaner.” The director requested the youth to show his hands. The youth showed a pair of hands that were smooth and perfect. The director asked, “Have you ever helped your mother wash the clothes before?” The youth answered, “Never, my mother always wanted me to study and read more books. Furthermore, my mother can wash clothes faster than me.” The director said, “I have a request. When you go back today, go and clean your mother’s hands, and then see me tomorrow morning.” The youth felt that his chance of landing the job was high. When he went back, he happily requested his mother to let him clean her hands. His mother felt strange, happy but with mixed feelings, she showed her hands to the kid. The youth cleaned his mother’s hands slowly. His tear fell as he did that. It was the first time he noticed that his mother’s hands were so wrinkled, and there were so many bruises in her hands. Some bruises were so painful that his mother shivered when they were cleaned with water. This was the first time the youth realized that it was this pair of hands that washed the clothes everyday to enable him to pay the school fee. The bruises in the mother’s hands were the price that the mother had to pay for his graduation, academic excellence and his future. After finishing the cleaning of his mother hands, the youth quietly washed all the remaining clothes for his mother. That night, mother and son talked for a very long time. Next morning, the youth went to the director’s office. The Director noticed the tears in the youth’s eyes, asked: “Can you tell me what have
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you done and learned yesterday in your house?” The youth answered, “I cleaned my mother’s hand, and also finished cleaning all the remaining clothes.” The Director asked, “Please tell me your feelings.” The youth said, Number 1, I know now what appreciation is. Without my mother, there would not be the successful me today. Number 2, by working together and helping my mother, only I now realize how difficult and tough it is to get something done. Number 3, I have come to appreciate the importance and value of family relationship. The director said, “This is what I am looking for to be my manager.” I want to recruit a person who can appreciate the help of others, a person who knows the sufferings of others to get things done, and a person who would not put money as his only goal in life. You are hired. Later on, this young person worked very hard, and received the respect of his subordinates. Every employee worked diligently and as a team. The company’s performance improved tremendously.
Lessons to be Learnt A child, who has been protected and habitually given whatever he wanted, would develop “entitlement mentality” and would always put himself first. He would be ignorant of his parent’s efforts. When he starts work, he assumes that every person must listen to him, and when he becomes a manager, he would never know the sufferings of his employees and would always blame others. For this kind of people, who may be good academically, may be successful for a while, but eventually would not feel sense of achievement. He will grumble and be full of hatred and fight for more. If we are this kind of protective parents, are we really showing love or are we destroying the kid instead? You can let your kid live in a big house, eat a good meal, learn piano, watch a big screen TV. But when you are cutting grass, please let them experience it. After a meal, let them wash their plates and bowls together with their brothers and sisters. It is not because you do not have money to hire a maid, but it is because you want to love them in a right way. You want them to understand, no matter how rich their parents are, one day their hair will grow gray, same as the mother of that young person. The most important thing is your kid learns how to appreciate the effort and experience the difficulty and learns the ability to work with others to get things done.
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LIGHTER READING
HUMOR
Lighter Side of Medicine ‘X’ MARKS THE SPOT Paul and Jim decided to rent a boat on a lake for their favorite sport. After fishing for 4 hours at various places around the lake with no luck at all they decided to try one more spot before calling it quits. Suddenly things started to happen, and they caught their limit inside of 20 minutes. Paul said, “Hey, we should mark this spot, so next time we will know where to come.” Jim says, “Good idea,” and he took out a can of spray paint and made a large X on the floor of the boat to mark the spot. With that Paul says, “Why did you do that? Now anyone who rents this boat will know where to fish!” NOW APPEAR CLEARER A patient on her second visit to the optometrist’s clinic: “I see specs before my eyes”. The optometrist asks, “Didn’t the new spectacles help?” The patient replies, “Sure, the specs now appear clearer.” TOMATOES
During this period all the signs and symptoms of insanity are absent. The person is responsible for all his acts performed during the period of lucid interval. GETTING RID OF THE PROBLEM A farmhand is driving around the farm, checking the fences. After a few minutes he radios his boss and says, “Boss, I’ve got a problem. I hit a pig on the road and he’s stuck in the bull-bars of my truck. He’s still wriggling. What should I do?” “In the back of your truck there’s a shotgun. Shoot the pig in the head and when it stops wriggling you can pull it out and throw it in a bush.” The farm worker says okay and signs off. About 10 minutes later he radios back. “Boss I did what you said, I shot the pig and dragged it out and threw it in a bush.” ”So what’s the problem now?” his Boss snapped. ”The blue light on his motorcycle is still flashing!”
Dr. Good and Dr. Bad SITUATION: A type 2 diabetic patient on insulin therapy, with comorbid
CAD and associated microvascular disorders wanted to know his odds of developing herpes zoster (HZ). One of his colleagues with diabetes had recently developed HZ.
A small boy was looking at the red ripe tomatoes growing in the farmer’s garden. “I’ll give you my two pennies for that tomato,” said the boy pointing to a beautiful, large, ripe fruit hanging on the vine. “No,” said the farmer, “I get a dime for a tomato like that one.”
THERE’S NO RELATION IN THESE CONDITIONS
YES, YOU ARE AT INCREASED RISK FOR HZ
The small boy pointed to a smaller green one, “Will you take two pennies for that one?”
WHAT IS LUCID INTERVAL? Lucid interval is the period during which the mentally unsound person behaves very much like a normal person.
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© IJCP Academy
“Yes,” replied the farmer, “I’ll give you that one for two cents.” “OK,” said the lad, sealing the deal by putting the coins in the farmer’s hand, “I’ll pick it up in about a week.” LESSON:
In a retrospective, study, there was a significantly higher risk of HZ in DM patients with accompanying CAD and microvascular disorders in comparison with DM patients with other comorbidities but no microvascular disorders. Moreover, patients who took thiazolidinedione, alpha-glucosidase inhibitors and insulin had a higher HZ risk than those taking metformin or sulfonylureas alone. PLoS One. 2016;11(1):e0146750.
Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter –
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The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.
Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures). –
The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.
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Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors. Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,
name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references. Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives. Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. –
Confidence intervals for the measurements should be provided wherever appropriate.
Results –
These should be concise and include only the tables and figures necessary to enhance the understanding of the text.
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Discussion –
This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.
References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.
Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. – The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. – Color illustrations will be accepted if they make a contribution to the understanding of the article. –
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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.
Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________
Books
5. Special requests _____________________________
Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.
6. Suggestions for reviewers (name and postal address)
Articles in Books
2.____________ 2.________________
Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.
3.____________ 3.________________
4.____________ 4.________________
Tables –
These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.
Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. –
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The legend must include enough information to permit interpretation of the figure without reference to the text.
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Indian 1.____________Foreign 1.________________
7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________
Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence
Dr KK Aggarwal
Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com
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