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Volume 24, Number 4

September 2013, Pages 301-400

Peer Reviewed Journal

yy American Family Physician yy Cardiology yy Dentistry yy Dermatology yy ENT yy Gastroenterology yy Infectious Diseases yy Internal Medicine

ian c i s hyhysicians P ly P

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Oncology

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IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor

Volume 24, Number 4, September 2013 from the desk of group editor-in-chief

305 Retained Sponge does not Always Mean a Bad Apple (Mistake of an Incompetent Doctor community health

Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal Group Editor-in-Chief Dr Veena Aggarwal MD, 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 ENT Dr Jasveer Singh Dr Chanchal Pal Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Orthopedics Dr J Maheshwari

Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

This journal is indexed in IndMED (http://indmed.nic.in) and full-text of articles are included in medIND databases (http://mednic.in) hosted by National Informatics Centre, New Delhi.

310 Sixty Percent of People do not Discuss their Sexual Behavior and Performance with the Doctor when they go for Consultation

KK Aggarwal

American Family Physician

312 Subacute to Chronic Mild Traumatic Brain Injury

Timothy F. Mott, Michael L. Mcconnon, Brian P. Rieger

319 Practice Guidelines 322 Photo Quiz CARDIOLOGY

324 Study of Association Between Metabolic Syndrome and Acute Coronary Syndrome

Virendra Dhakhada, Madhu Panjwani, Ajay Dabhi

Dentistry

330 Endodontic Management of Cutaneously Draining Odontogenic Sinus using Shoe Lace Technique

Sumit Mohan

Dermatology

336 Nevus of Ota is a Rare Nevus and Q-switched Laser is the Best Available Option for Successful Treatment

OP Patidar, Rekha Patidar

ENT

339 Papillary Thyroid Carcinoma Presented as Cystic Neck Mass: A Rare Presentation

Santosh Kumar Pratinidhi, Sanjay Panda, Dillip Das

342 Interval Tonsillectomy: 27 Cases of Peritonsillar Abscesses Managed in Medical College Hospital

Sudhir M Naik, Sarika S Naik

Gastroenterology

347 Pseudomembranous Colitis: Do We Need A Screening?

Ashish Gautam, Prabhat Agrawal, Abhishek Raj, Ashwini K Nigam, Subhash Chandra, Manish K Bansal

Infectious Diseases

351 Serostatus Disclosure and Safer Sex in HIV-positive Man: Case Study

Sangita Patel, Shilpa N Patel, Rajendra K Baxi, Carol E Golin, Kedar Mehta, Mansi Mehta, Harsh Bakshi, Kalpita Shingrapure, Ekta Modi, Priyanka Coonor

353 HIV and Infant Feeding

VK Agrawal

357 How to Manage Hepatitis B Infection?

Deepak Amarapurkar, Nikhil Patel

Internal medicine

360 Clinical and Laboratory Evaluation of Patients with Fever with Thrombocytopenia

Shankar R Raikar, Panna K Kamdar, Ajay S Dabhi


Neurology 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

364 Communication Between Musculocutaneous and Median Nerve – Different Types and Their Incidence in North Indian Population

Priti Chaudhary, Gurdeep Kalsey, Ranjan Singla, Kamal Arora

obstetrics and gynecology Printed at New Age Communications Pvt. Ltd., New Delhi E-mail: edgecommunications@gmail.com

372 Fetal Femur Length in Assessment of Gestational Age in Third Trimester in Women of Northern India (Lucknow, UP) and a Comparative Study with Western and Other Asian Countries

© Copyright 2013 IJCP Publications Ltd. All rights reserved.

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.

DP Gupta, DK Saxena, Hem Prabha Gupta, Zaidi Zeeshan, RP Gupta

Oncology

376 Prognostic Impact of CD3 Tumor Infiltrating Lymphocytes in Triple-negative Breast Cancer

Editorial Policies

Ankita Singh Rathore, Madhu Mati Goel, Annu Makker, Sandeep Kumar, AN Srivastava

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Ophthalmology

381 Effect of Environment on Eyes: A Review Shubhrica

PHARMACOLOGY

385 Torsemide: A New Loop Diuretic

M Vadivelan, AS Dabhi

mediLAW

389 When can Hospitals be Liable for Medical Negligence Deaths? KK Aggarwal

emedinews inspiration

392 The Tiger’s Whisker

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.

eMedi quiz

393 Quiz Time lighter reading

396 Lighter Side of Medicine

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Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, Elect, IMA Chairman, Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Retained Sponge does not Always Mean a Bad Apple (Mistake of an Incompetent Doctor)

T

he most common retained foreign body during surgery is a woven cotton surgical sponge, which includes both laparotomy pads and smaller sponges. Sponges are easily retained because of their ubiquitous use, relatively small size and because, when soaked in blood, sponges conform to and can be difficult to distinguish from surrounding tissues. The problem of retained surgical sponge is known as gossypiboma, and also as ‘textiloma’, ‘gauzoma’ or ‘muslinoma’. The word gossypiboma may have been formed from the Latin ‘gossypium’ meaning ‘cotton’ and Swahili ‘boma’ meaning ‘place of concealment’ or the word ‘oma’ may have been added to gossypi to indicate a growth, as in the example textiloma. Surgical instruments, needles and other items can also be inadvertently left behind in surgical fields. Clamps and retractors are the most common types of retained instruments, but items such as electrodes, electrocautery scratch pads, drains and pieces of suction tubing have also been described. It is estimated that retained surgical foreign bodies occur one in every 5,500-18,760 inpatient operations but the incidence may be as high as one out of every 1,000-1,500 abdominal cavity operations, and even more common during emergency surgeries. In a retrospective review from a Level I trauma center, three cases of retained foreign bodies (all sponges) occurred in 2,075 trauma laparotomies over an 8-year period, for an incidence of approximately one in 700. Intuitively, laparoscopic, endoscopic and percutaneous procedures are less likely to lead to a retained sponge or instrument. The incidence of retained sponge depends, in part, upon the anatomic location of the procedure. Retained sponges in adults occur most commonly in the abdomen (56%), pelvis (18%) and thorax (11%). However, it has been described with spinal, extremity, intracranial, vascular, breast, pediatric and even facial plastic surgery procedures. As per a report from Mahran Group from Norfolk and Norwich University Hospital, UK published in August 2013 issue of Best Practice and Research Clinical Obstetrics and Gynaecology, one case of a retained item occurs at least once a year in a major hospital where 8,000-18,000 major cases are carried out each year. In another report published in November-December 2010 issue of Chirurgia (Bucur). Andronic and group reported the incidence of retained textile foreign body to be in the range of 1:833-1:32672. In their center, the incidence was 1:15047. Facts about gossypibomas ÂÂ Gossypibomas are surgical sponges that are UNINTENTIONALLY left inside a patient during a surgical

procedure. They are unavoidable and will continue to occur in third world countries but as per a Stanford University School of Medicine California study, multidisciplinary approaches and new technologies may help reduce this low frequency but clinically significant event.

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from the desk of group editor-in-chief ÂÂ However, given the complexity of surgical care, eliminating retained sponges may prove elusive. Unless no

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ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ ÂÂ

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precautions were taken they thus can attract a compensation under the law of torts but definitely not a criminal charge under Indian Penal Code (IPC) or suspension of a license. The medicolegal ramifications of retained surgical foreign body for the surgeon can be significant. The fact that an instrument or sponge has been left behind is considered proof that malpractice has occurred. Compensatory damage awards are commonly assigned to the surgeon as well as the hospital who is the employer of the operating room staff. The most common retained surgical foreign body is a surgical sponge, also known as gossypiboma. Retained surgical sponges and other surgical foreign bodies unintentionally left at surgical sites are rare medical errors that have the potential to cause significant harm to the patient. Retained items are among a group of completely preventable medical errors that are always considered wrong. The mean age of patient with this complication is 49 years (range 6-92 years). It is most commonly found in the abdomen (56%), pelvis (18%) and thorax (11%). Average discovery time equals 6.9 years (standard deviation [SD] 10.2 years) with a median (quartiles) of 2.2 years (0.3-8.4 years). The most common detection methods are computed tomography (CT) (61%), radiography (35%) and ultrasound (34%). Pain/irritation (42%), palpable mass (27%) and fever (12%) are the leading signs and symptoms, but 6% of cases are asymptomatic. Very long-standing retained surgical sponge is associated with a particular pattern of calcification termed the reticulate rind sign. Complications include adhesion (31%), abscess (24%), and fistula (20%). Risk factors are case specific (emergency) or related to the surgical environment (poor communication).

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Emergency surgical procedures (risk ratio [RR] 8.8, 95% CI 2.4-31.9)

zz

Unexpected change in the course of a surgical procedure (RR 4.1, 95% CI 1.4-12.4)

Increased body mass index (RR per 1-unit increment 1.1, 95% CI 1.0-1.2) ÂÂ Most gossypibomas occur when the sponge count is falsely pronounced correct at the end of surgery. ÂÂ Though rare it is therefore possible to have a surgical swab left in the first surgery, remains asymptomatic and gets detected and becomes symptomatic after the second surgery. ÂÂ One must remove all symptomatic retained surgical foreign bodies. There may be a role for observational management in asymptomatic patients, particularly if the retention time has been prolonged, given that operative removal of retained sponges can be difficult and is associated with significant morbidity and mortality. zz

Prevention ÂÂ To improve this patient safety indicator, anesthesiologists will need to work with operating room personnel. ÂÂ Multidisciplinary approaches are required. ÂÂ The first step is strict swab or sponge counting before and after surgery. ÂÂ Another is avoidance of change of staff during procedures. ÂÂ Improving communication between the members of the surgical team. ÂÂ New technologies may help reduce this low frequency but clinically significant event. ÂÂ However, given the complexity of surgical care, eliminating retained sponges may prove elusive. ÂÂ Various national authorities have issued regulations to prevent RTFB, based on counting compresses

306

zz

Intra-/postoperative radiography

zz

Marking compresses with two-dimensional matrix label

zz

Radiofrequency identification.

zz

Radioopaque sponges.

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013


from the desk of group editor-in-chief zz

Tracking devices that use electronic tagging increase the accuracy of sponge counts (bar coding) and reliably identify retained sponges (radiofrequency identification), but these technologies are costly, and thus, have not been widely adopted.

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Although human errors cannot be completely abolished, continuous medical training and strict adherence to regulations should reduce the incidence to a minimum but not zero.

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With the increasing use of minimally invasive procedures, the incidence will fall dramatically.

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Given the limitations of the surgical count, particularly under emergency circumstances, many prefer to obtain a radiograph of the operative field (open cavity surgery) prior to patient transport in high-risk patients. In patients with a low-risk for retained surgical foreign object, one can employ selective radiographic screening.

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If a lap pad count is reported to be incorrect, and the pad cannot be found by the surgeon, X-ray of the abdomen is mandatory. Care must be taken to be sure the entire abdomen, from below the symphysis to above the hemidiaphragms, is included in the film. However, most retained lap pads occur in cases in which the lap pad count, even multiple counts, is reported to be correct. Removal of a retained lap pad may be very difficult, due to extensive adhesions. Towels are infrequently placed within the abdomen, and in many hospitals they are not a counted item, creating potential for their being retained.

How to escape liability ÂÂ Both surgeons and anesthetists will be liable along with the nursing staff. ÂÂ For the nurse, the medical administrator may be vicariously liable if the surgeon and the anesthetists are

honorary consultants (fee for service contract).

ÂÂ To escape liability under an enquiry the hospital and operative surgeons need to show the following: ÂÂ That there is a system in place regarding prevention of gossypibomas. Under the system the surgical swabs

and instruments are counted before and after the surgery in every case. And the same is documented before and after the surgery in the case sheet.

ÂÂ That in establishments with large surgical volume and in emergent situations special precautions is taken to

avoid this.

ÂÂ That there are special training sessions held for the nurses and OT technical staff to prevent preventable errors

on OT (Fire, retained gauzes and instruments and wrong site surgery).

ÂÂ That they have an in house system of informed consent, where it is documented that retained sponge is a

known complication and can occur in spite of all possible corrective measures.

MEDICOLEGAL IMPLICATIONS ÂÂ Retained surgical materials are considered ‘always wrong,’ mandating acknowledgment, direct apology to the

patient and hospital payment for all costs incurred as a result.

ÂÂ In most jurisdictions, the legal doctrine applied to the problem of a retained surgical sponge is res ipsa

loquitor, ‘the thing speaks for itself’. The fact that a surgical foreign object has been retained is, in itself, proof that malpractice has occurred. It is also important to note that the statutes of limitations for retained foreign body in most jurisdictions are generally extended indefinitely, rather than fixed to a 2- or 3-year term as in other cases of medical malpractice. Thus, one may be able to sue 20 years later for a foreign body that was undiscovered.

ÂÂ In a review of closed case files in Massachusetts, 40 patients were found to have retained sponges over a

7-year period representing about half of the claims of retained foreign bodies during that period. Eleven were vaginal sponges retained after vaginal delivery, and these were presumably removed at the bedside, without requiring laparotomy. Total compensatory damage awards for the 40 actions were $2,072,318, with $1,762,163 (85%) made on behalf of the surgeon and $909,705 (15%) on behalf of the healthcare institution. Five cases (10%) went to trial. A median of $68,857 and a mean of $32,500 were spent on claims involving abdominal procedures. The time period between discovery of the sponge and the original procedure was significantly related to the case payment, with higher payments reflecting delayed discovery and

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from the desk of group editor-in-chief difficulties and complications associated with surgical removal. Two patients declined removal of the retained sponge because they were asymptomatic, but filed claims for damages anyway. ÂÂ In several cases, a verdict has been returned against the surgeon in spite of a correct sponge count.

The surgeon can be held responsible for his or her own failure to examine the field and look and/or feel for foreign bodies independent of the staff’s responsibility to perform accurate counts. The duties are parallel, and one responsibility does not relieve the other.

ÂÂ Payments for claims for retained sponges may be greater in jurisdictions where no cap on noneconomic

damages exists. Among three studies, the average payment for retained surgical foreign body was estimated at $95,000, a figure that included $14,701 for readmission and reoperation and the remainder in lost wages and pain/suffering. In a review of over 1000 cases reported to the National Practitioner Data Bank over a 7-year period, retained surgical foreign body resulted in a mean compensation of $77,175. The maximum payment was $2,350,000.

Indian judgments In all Indian judgments the negligence has been tried under the law of torts. Never events are situations where deficiency of service and or negligence is presumed and no trial of expert’s evidence is necessary. Following are examples rectified by various court judgments. ÂÂ Relatives found a pair of scissors while collecting the last remains Compensation of `. 1.20 lakhs. ÂÂ Mop left in abdomen, 2nd surgery, death (doctrine of res ipsa loquitur applicable). ÂÂ The issues arising in the complaints in such cases can be speedily disposed of by the procedure that is being

followed by the Consumer Disputes Redressal Agencies and there is no reason why complaints regarding deficiency in service in such cases should not be adjudicated by the Agencies under the Act.”

SUMMARY Despite the precautions, the retention of foreign bodies still occurs. Gossypiboma should always be considered in the differential diagnosis of indeterminate abdominal pain, infection or a mass in patients with a prior surgical history. Suggested Reading 1. Gawande AA, Studdert DM, Orav EJ, Brennan TA, Zinner MJ. Risk factors for retained instruments and sponges after surgery. N Engl J Med 2003;348(3):229-35. 2. Cima RR, Kollengode A, Garnatz J, Storsveen A, Weisbrod C, Deschamps C. Incidence and characteristics of potential and actual retained foreign object events in surgical patients. J Am Coll Surg 2008;207(1):80-7. 3. Hyslop JW, Maull KI. Natural history of the retained surgical sponge. South Med J 1982;75(6):657-60. 4. Teixeira PG, Inaba K, Salim A, Brown C, Rhee P, Browder T, et al. Retained foreign bodies after emergent trauma surgery: incidence after 2526 cavitary explorations. Am Surg 2007;73(10):1031-4. 5. Wan W, Le T, Riskin L, Macario A. Improving safety in the operating room: a systematic literature review of retained surgical sponges. Curr Opin Anaesthesiol 2009;22(2):207-14. 6. Naama O, Quamous O, Elasri CA, Boulahroud O, Belfkih H, Akhaddar A, et al. Textiloma: an uncommon complication of posterior lumbar surgery. J Neuroradiol 2010;37(2):131-4. 7. Mouhsine E, Halkic N, Garofalo R, Taylor S, Theumann N, Guillou L, et al. Soft-tissue textiloma: a potential diagnostic pitfall. Can J Surg 2005;48(6):495-6. 8. Kim AK, Lee EB, Bagley LJ, Loevner LA. Retained surgical sponges after craniotomies: imaging appearances and complications. AJNR Am J Neuroradiol 2009;30(6):1270-2. 9. Haegeman S, Maleux G, Heye S, Daenens K. Textiloma complicated by abscess-formation, three years after surgical repair of abdominal aortic aneurysm. JBR-BTR 2008;91(2):51-3. 10. El Khoury M, Mignon F, Tardivon A, Mesurolle B, Rochard F, Mathieu MC. Retained surgical sponge or gossypiboma of the breast. Eur J Radiol 2002;42(1):58-61. 11. Camp M, Chang DC, Zhang Y, Chrouser K, Colombani PM, Abdullah F. Risk factors and outcomes for foreign body left during a procedure: analysis of 413 incidents after 1 946 831 operations in children. Arch Surg 2010;145(11):1085-90.

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from the desk of group editor-in-chief 12. Song SY, Hong JW, Yoo WM, Tark KC. Gossypiboma after mandibular contouring surgery. J Craniofac Surg 2009;20(5): 1607-10. 13. Mahran MA, Toeima E, Morris EP. The recurring problem of retained swabs and instruments. Best Pract Res Clin Obstet Gynaecol 2013;27(4):489-95. 14. Andronic D, Lupaşcu C, Târcoveanu E, Georgescu S. Gossypiboma--retained textile foreign body. Chirurgia (Bucur) 2010;105(6):767-77. 15. Kaiser CW, Friedman S, Spurling KP, Slowick T, Kaiser HA. The retained surgical sponge. Ann Surg 1996;224(1):79-84. 16. Jackson, JZ. A primer on the unhappy defense of the surgeon in a retained sponge case. Med Law Update 2003;3:10. 17. Stawicki SP, Evans DC, Cipolla J, Seamon MJ, Lukaszczyk JJ, Prosciak MP, et al. Retained surgical foreign bodies: a comprehensive review of risks and preventive strategies. Scand J Surg 2009;98(1):8-17. 18. Nihal Kaur v. Director, PGI, Chandigarh. 1996;3 CPJ 112 (Chandigarh (UT) CDRC). 19. Achutrao Haribhau Khodwa & ors. vs State of Maharashtra and Ors. (1996) 2 SCC 634. 20. 334/2005/SCI/ 144-145 of 2004: Jacob Mathew vs State of Punjab and Anr: 5th August 2005: R C Lahoti, CJI: Hon’ble Mr. Justice G P Mathur, Hon’ble Mr. Justice P K Balasubramanyan. 21. SC/4119 of 1999 and 3126 of 2000, 14.05.2009, Nizam Institute of Medical Sciences Vs. Prasanth S. Dhananka and Ors.: B.N. Agrawal, Harjit Singh Bedi and G. S. Singhvi, JJ. 22. Haralur SB, Shah FK. Maxillofacial prosthesis in a palliative care for terminally ill patient with squamous cell carcinoma. BMJ Case Rep 2013 Jun 21;2013. ■■■■

Me Lord I am not Guilty: Safety program protocol We regret that such incident has occurred but the fall was accidental. He fell despite side rails on the bed. Our hospital has a safety first program that aims to proactively identify patients at risk for fall.

The case is dismissed. As long as the hospital follows a safety program. Such accidents can still occur despite all preventive measures.

Proceed

My father fell down from the bed while in the hospital and ultimately died.

Lesson: In an order dated DMC/DC/F14/256/2006, the Council highlighted the laws of safety programs protocol being followed in a hospital. If the same could not have been documented, the accident could have accounted for as negligence.

Dr. K K Aggarwal, Padma Shri and Dr. B C Roy National Awardee; Chairman Legal Cell Indian Academy of Echocardiography; Editor eMedinewS and President Heart Care Foundation of India

Dr. KK Aggarwal

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309


community health

Sixty Percent of People do not Discuss their Sexual Behavior and Performance with the Doctor when they go for Consultation KK Aggarwal

Abstract On Doctor’s Day 2013 a survey was conducted to assess the perception of doctor-patient relationship among the people and the expectations of the patients from the doctors. Data was collected using a questionnaire came up with some interesting changing trends among the people with regard to doctor-patient relationship.

Keywords: Family physician, specialist, sexual history, etiquette based medicine, privacy, health insurance

A

survey of 452 people was conducted by Heart Care Foundation of India and eMedinewS on the occasion of Doctors Day 2013. The objective of the survey was to assess the perception of doctor-patient relationship among the people and the expectations of the patients from the doctors. The survey included patients, social workers, RWAs, morning walkers, college students and government employees from NCR Delhi and consisted of middle to high socioeconomic strata. Data was collected using a questionnaire, which the survey participants were asked to answer. The data came up with some interesting changing trends among the people with regard to doctor-patient relationship.

New trend to directly go to specialists The survey revealed that only 42% had a family physician. When suffering from an illness, 52% of the people would directly opt to visit a specialist and not a family physician, which is not a good trend. The traditional concept of a ‘family physician’ that looked after all the health needs of a family regardless of his/ her specialization, is now changing.

shy coming out with the history as most of the times patients are accompanied by the relations. The survey found that 60% of the patients have never opened out to their doctors and 80% of the doctors have never asked then about the sexual history. This brings them to seek help from sex quacks and advise from friends and neighborhood. The survey found that people are sexually active even at elderly age. The proportion of man reporting no sex is 20% at age 51-60 and 87.5% at age above 75. In women, reporting no sex is 100% after the age of 70. About 16.17% of men reported that they are facing erectile dysfunction and 17.64% are having premature ejaculation during sexual act. The survey enlisted that the public wanted the following to be asked to them in isolation in person or through a document about the following: ÂÂ Are you sexually active ÂÂ Are you satisfied with your sexual life ÂÂ Are you sexually attracted to men, women or both ÂÂ Do you have multiple partners

Sexual preferences, choices and behaviors

People want experienced doctors

Eighty percent of the people want their doctors to ask about the sexual history in confidence. They feel

Sixty-five percent prefer senior doctors with white hair to treat them as they can provide better patient care than their younger fashionable counterparts with less clinical experience. Hundred percent of the people said that if their doctor cannot practice ‘compassion based medicine’ at least practice ‘etiquette-based medicine’.

Padma Shri & Dr BC Roy National Awardee President Heart Care Foundation of India E-mail: emedinews@gmail.com

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community health Sixty percent of the people put their faith in the capabilities of their doctor and not on their dress code. Fifty-seven percent however check the credentials and qualifications of a doctor before visiting them for consultation. This is a new trend in the society. When asked about the criteria of a good doctor 90% people said that for them availability and behavior of a doctor is more important than competency. “What is the use of a competent doctor if he is not available and is arrogant”: Was the common question asked by them? When questioned about the etiquette based medicine, 84% people said that they would like their doctor to call them with their name; would like the doctor to introduce about his credentials and competency; would like to explain and reason out the plan and duration of treatment. Patients want privacy Forty percent of the people did not want doctors to be their friends on Facebook. New International guidelines also warn doctors not to be connected with their patients on facebook. Eighty percent of the people wanted that their personal health information should not be leaked to any one without asking them including the spouse and their name should not be shouted outside the operation theatre or the intensive care unit (ICU). Patients do not like smoking doctors Eighty-one percent people reported being disturbed when they saw their doctors smoking in public and would not like to be treated by a doctor who smoked in front of them. Patients want doctors to write legibly Sixty-seven percent people felt that their doctors should have legible handwriting and favored an electronic prescription instead. Patients want affordable, quality and safe medical care Seventy-eight percent people felt that medical profession is becoming commercialized today and should be made more affordable for a common man. Seventy-two percent people said that doctors should be transparent in their fee. Fifty-nine percent people felt that doctors’ charging less fee is not their concern. But, 41% were of the opinion that doctors should charge less as their profession is a noble one.

Patients want doctors to spend more time with them Forty-nine percent people reported being satisfied with less 15 minutes of a doctor’s time; 26% wanted their doctor to spend more than 15 minutes with them and the rest wanted time till they were satisfied. Fifty-four percent people said that their doctors never advised them about adult vaccination. This needs immediate attention. Fifty-five percent said that their blood pressure had never been checked in both arms. Fortynine percent people said that they would prefer to take a dietary advice from their doctor and not from a dietitian. Patient wants second opinion from the same doctor Sixty percent people wanted to get a second opinion from their regular doctor if they are not satisfied. Seventy-two percent people do not want doctors to treat them just on clinical grounds but prefer getting investigated first. When advised investigations, 57% would ask their doctor to suggest a lab, while the rest said that they would choose their own lab. Patient etiquette Forty-six percent people said that they preferred to call their doctor directly to fix an appointment and not the secretary. When calling for an appointment, 53% would choose to call on a mobile number and not the landline, whether the call is to the doctor or the secretary. Ignorance is still high ÂÂ Forty-seven percent persons did not have any

health insurance.

ÂÂ Forty-nine percent did not know that when they are

hiring a room in a private hospital, the insurance covers only 1% of the sum amount insured for the bed.

ÂÂ Fifty-two percent of the people do not know that

error of judgment or difference of opinion is not an act of negligence on the part of the doctor.

ÂÂ Forty-eight percent people were unaware of the

fact that a doctor is supposed to possess only an average degree of skill and knowledge and not the maximum degree of skill and knowledge when treating a patient.

ÂÂ Thirty percent of the people were unaware that

creating violence in the hospital premises is an offence.

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American Family Physician

Subacute to Chronic Mild Traumatic Brain Injury TIMOTHY F MOTT, MICHAEL L McCONNON, BRIAN P RIEGER

Abstract Although a universally accepted definition is lacking, mild traumatic brain injury and concussion are classified by transient loss of consciousness, amnesia, altered mental status, a Glasgow Coma Score of 13 to 15, and focal neurologic deficits following an acute closed head injury. Most patients recover quickly, with a predictable clinical course of recovery within the first one to two weeks following traumatic brain injury. Persistent physical, cognitive, or behavioral postconcussive symptoms may be noted in 5 to 20 percent of persons who have mild traumatic brain injury. Physical symptoms include headaches, dizziness, and nausea, and changes in coordination, balance, appetite, sleep, vision, and hearing. Cognitive and behavioral symptoms include fatigue, anxiety, depression, and irritability, and problems with memory, concentration and decision making. Women, older adults, less educated persons, and those with a previous mental health diagnosis are more likely to have persistent symptoms. The diagnostic workup for subacute to chronic mild traumatic brain injury focuses on the history and physical examination, with continuing observation for the development of red flags such as the progression of physical, cognitive, and behavioral symptoms, seizure, progressive vomiting, and altered mental status. Early patient and family education should include information on diagnosis and prognosis, symptoms, and further injury prevention. Symptom-specific treatment, gradual return to activity, and multidisciplinary coordination of care lead to the best outcomes. Psychiatric and medical comorbidities, psychosocial issues, and legal or compensatory incentives should be explored in patients resistant to treatment.

Keywords: Mild traumatic brain injury, concussion, postconcussive symptoms, cognitive and behavioral symptoms, multidisciplinary coordination

W

ith the wars in Iraq and Afghanistan, and with increased attention to athletes who experience concussions, there is a heightened awareness of traumatic brain injury. Improved guidelines on how to evaluate and manage concussion and mild traumatic brain injury (MTBI) in the acute setting have been developed, but confusion remains about accurate diagnosis and treatment in the subacute and chronic setting.1,2 Varying definitions of concussion and MTBI, combined with the relative lack of evidence on long-term care and outcomes, contribute to this uncertainty (Table 1).3-8 As a means of convention, the term MTBI will be used for MTBI and concussion in this review. Epidemiology Approximately 1.7 million persons experience traumatic brain injury annually, with 75 percent of cases being MTBI.7,9 Children four years and younger, young persons 15 to 19 years of age, and older adults

Source: Adapted from Am Fam Physician. 2012;86(11):1045-1051.

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are most susceptible to MTBI, with falls being the most common etiology among patients older than 75 years. Men are more likely at every age to experience acute traumatic brain injury than women, although women are more likely to have subacute to chronic sequelae. Most patients with MTBI improve over the first few hours to days, but 5 to 20 percent may continue to have postconcussive symptoms for an extended period following the initial injury10,11 (Tables 28 and 38). Women, older adults, less educated persons, and those with a previous mental health diagnosis are prone to persistent symptoms. In the United States, direct and indirect costs of MTBI in 2000 were estimated to be $12 billion.12 Traumatic brain injury is described as the signature injury of military personnel serving in Operation Enduring Freedom and Operation Iraqi Freedom, with as many as 15 percent of combatants experiencing this type of injury.13,14 The precise incidence is debatable, largely because of disparity in definitions and overlap with other conditions.8 Use of the term postconcussive syndrome should be discouraged because many of the symptoms are subjective and difficult to predict consistently. They also occur in persons who do not have a traumatic brain injury, but who may have mental health


Other symptoms/findings

Symptoms must not be related to penetrating head injury, intoxicants or other medications, or other diagnoses

Transient‡

30 minutes or less‡

Initial score of 13 to 15, 30 minutes after injury or later on presentation to care Not requiring surgery

Transient‡

30 minutes or less

Definition specifically — for concussion in sports; concussion may also occur with impulsive force transmitted to the head

May occur in a small — subset of patients — —

May or may not occur

None visible on imaging

Transient

Around the time of injury

Transient

Centers for Disease Control and Prevention7

Specifically uses terms concussion and mild traumatic brain injury interchangeably

30 minutes or less

None visible on imaging

Best score in first 24 hours of 13 to 15

Posttraumatic amnesia for less than one day

U.S. Department of Veterans Affairs/ Department of Defense 8 Transient up to 24 hours

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

include one of the following: loss of consciousness, amnesia, altered mental status, focal neurologic deficit, or seizure.

Information from references 3 through 8.

‡Must

is a complex pathophysiologic process that affects the brain and is induced by traumatic biomechanical forces. It typically involves transient neurologic impairment that resolves spontaneously as well as a stepwise course of clinical and cognitive symptom resolution, with 80 to 90 percent of concussions resolving in seven to 10 days.

†Concussion

*Unless otherwise stated, all definitions include having one or more of these symptoms or diagnostic findings following a nonpenetrating injury to the head. Symptoms left blank imply not being specifically addressed by the respective guideline.

Definition specifically for concussion in sports; symptoms may be divided into early and late categories, and may vary from case to case

Grades 1-2, none; grade 3, seconds to minutes

Postconcussive syndrome Seizure

Intracranial lesion

30 minutes or less

Initial score of 13 to 15

Glasgow Coma Score

Loss of consciousness

Any

Less than 24 hours‡

Grade 1, posttraumatic amnesia < 15 minutes; grade 2, posttraumatic amnesia > 15 minutes —

Posttraumatic amnesia less than 24 hours; any retrograde amnesia

Transient

Transient‡

Grade 1, < 15 minutes; grade 2, > 15 minutes

Any

Zurich Consensus Statement 6†

World Health Organization5

American Academy of Neurology4

American Congress of Rehabilitation Medicine3

Guideline

Focal neurologic deficit

Altered mental status or alteration of consciousness (e.g., feeling dazed, disoriented, confused) Amnesia

Symptom/diagnostic finding*

Table 1. Definitions of Mild Traumatic Brain Injury

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American Family Physician Table 2. Concussion and Mild Traumatic Brain Injury: Treatment of Common Persistent Behavioral and Cognitive Symptoms Symptom

Pharmacologic treatment*

Referral after poor response to treatment

Anxiety

Anxiolytic drugs (short-term), SSRIs

Mental health referral, social support

Cognitive problems (e.g., trouble with concentration, memory, and decision making)

Consider pharmacologic treatment after ruling out sleep disorders’ SSRIs

Consider referral to mental health services, cognitive rehabilitation, or traumatic brain injury subspecialist

Emotional problems (e.g., depression, irritability, poor frustration tolerance)

Antiepileptic drugs, SSRIs

Mental health referral, social support

Fatigue (e.g., loss of energy, easily tired) Consider pharmacologic treatment after ruling out sleep disorders

Mental health referral

Note: Nonpharmacologic treatment for all symptoms includes reassurance, regular aerobic exercise, activity restriction, sleep hygiene education, and referral for sleep studies. SSRI = selective serotonin reuptake inhibitor. *Additional information on pharmacologic treatment is available in appendix E of the U.S. Department of Veterans Affairs/Department of Defense clinical practice guideline for management of concussion/mild traumatic brain injury.

Table 3. Concussion and Mild Traumatic Brain Injury: Treatment of Persistent Physical Symptoms Symptom

Pharmacologic treatment*

Nonpharmacologic treatment

Referral considerations if poor response to treatment†

Change in appetite

Consider mental health referral

Dizziness

Antibiotics, decongestants for middle ear infections and fluid

ENT referral; neurology referral after ENT interventions

Headache

Non-narcotic analgesics, nonsteroidal anti-inflammatory drugs; triptans (for migraine)

Sleep hygiene education, physical therapy, relaxation

Neurology referral, pain clinic

Hearing problems (e.g., sensitivity to noise)

Environmental modifications

Audiology or ENT referral; speech and language pathology referral for patients with sensitivity to noise

Loss of balance, poor coordination

Physical therapy

Neurology referral

Nausea

Antiemetics

Sleep hygiene education

Gastroenterology referral

Sleep disturbances

Sleep medications

Sleep hygiene education

Mental health, neurology, or physical medicine and rehabilitation referral

Vision problems (e.g., blurring, photophobia)

Sleep hygiene education, light desensitization, sunglasses

Optometry or ophthalmology referral‡

ENT = Ear, nose, and throat. *Additional information on pharmacologic treatment is available in appendix E of the U.S. Department of Veterans Affairs/Department of Defense clinical practice guideline for management of concussion/mild traumatic brain injury. †Because all subspecialists are not equally proficient or current in the treatment of mild traumatic brain injury, it may be beneficial to determine the best local or regional referral options, including concussion and traumatic brain injury specialty clinics. ‡Depending

on local resources, patients with impaired vision may be referred to a neuro-ophthalmologist. Impaired vision may result from problems with oculomotility or from disorders of the retina and visual pathways.

disorders, chronic pain syndromes, and other disease processes.8,15 Postconcussive symptoms are equally prevalent in patients with MTBI and non–head injury trauma.16 The overlap of MTBI symptoms with those

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of other disease processes in patients who may have extenuating circumstances can complicate a workup. For example, patients seeking compensation or who are involved in litigation may exaggerate symptoms,


American Family Physician whereas athletes seeking expedited return to play may minimize symptoms.5,17 Clinical Presentation The most common physical symptom in the days to weeks following the initial injury is headache.8 Other symptoms include nausea, blurred vision, fatigue, and sleep disturbances. Typically, most patients will notice improvement in these symptoms within 24 hours of the injury; some studies of patients with MTBI show that within seven days of the injury, the symptom score was equal to that of control groups of patients who did not have MTBI.18 Cognitive symptoms occurring in patients following MTBI include attention difficulties, memory problems, and executive dysfunction (a decreased ability to organize activities and thoughts, and to plan and reason effectively). These symptoms are typically mild and difficult to detect on routine testing. Patients with these symptoms often describe a slowing of their thought processes. These symptoms typically improve in the first two to four weeks following the injury; however, a small percentage of patients may have prolonged symptoms.8,15 Behavioral symptoms that may occur following MTBI include irritability, mood and sleep disturbances, and fatigue. Persons with preexisting depression, anxiety, posttraumatic stress disorder, or substance abuse disorders are at much higher risk of MTBI symptoms.8,15 Other factors that promote post-injury behavioral symptoms include lower functional and socioeconomic status8,19 (Table 4).8 Diagnostic Evaluation The diagnostic evaluation of acute MTBI has been discussed previously in American Family Physician and more recently by other organizations.6,8,20,21 Guidelines issued by the U.S. Department of Veterans Affairs and the U.S. Department of Defense outline the management of subacute to chronic MTBI (Figure 1).8 Because patients can present with a range of symptoms, the diagnostic workup of subacute to chronic MTBI focuses on the specific nature of each patient’s symptoms and physical examination findings. The physical examination should include a neurologic examination focusing on the patient’s mental status, the cranial nerves, deep tendon reflexes, strength, gross cutaneous sensation, and postural stability.8 Physicians should also assess visual acuity, visual fields, and eye movements, and conduct a focused musculoskeletal

A Concussion or mild traumatic brain injury diagnosed; persistent symptoms beyond four to six weeks; initial treatment ineffective Reassess symptom severity and functional status; complete psychosocial evaluation* Are symptoms and functional status improved?

Yes

Assess for possible alternative causes for persistent symptoms; consider behavioral component (e.g., sleep or mood disorder) Yes Any behavioral health disorder diagnoses established (e.g., depression, traumatic stress, anxiety, substance abuse disorder)? No

Initiate or continue symptomatic treatment; reassure patient and family and provide educational materials

Manage comorbid conditions

Consider referral to mental health services for evaluation and treatment

Any persistent symptoms (e.g., physical, cognitive, emotional)?

No

Yes

Refer for further evaluation and treatment† Consider referral to occupational or vocational therapy and community integration programs; continue case management Encourage and reinforce; monitor for comorbid conditions Follow up and reassess in three to four months Go to A Figure 1. Management of concussion and mild traumatic brain injury. *Evaluation should include the patient’s support system, a mental health history, a review of any comorbid conditions (e.g., chronic pain, mood disorders, stress disorder, personality disorder), the possibility of a substance use disorder, any secondary gain issues (e.g., compensation, litigation), and whether the patient is unemployed or has had a change in job status. †Patients

should be referred to a family physician or multidisciplinary concussion management center. These should include at least one physician and may include the following: neuropsychologists; counselors; case managers; and speech, occupational, and physical therapists.

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American Family Physician Table 4. Risk Factors for Persistent Symptoms and Poorer Overall Outcomes with Mild Traumatic Brain Injury Before injury

At time of injury

After injury

Age (older)

Acute symptom presentation (e.g., headaches, dizziness, or nausea in the emergency department)

Chronic pain conditions

Less education or lower levels intelligence Low socioeconomic status Mental health disorders (e.g., depression, anxiety, traumatic stress, substance use)

Context of injury (e.g., stress, combat-related, traumatic) Lack of support system

Neurologic conditions

Compensation Lack of support system Less education Litigation (e.g., malingering, delayed resolution) Psychiatric disorders

Sex (female)

Table 5. Red Flags in Patients with Head Injury Altered consciousness

Pupillary asymmetry

Behaves unusually or seems confused and irritable

Repeated vomiting Seizures

Cannot recognize persons that the Slurred speech patient should be able to Unsteady on feet recognize, or is disoriented to place Double vision

Weakness or numbness in arms or legs

Progressively declining neurologic examination

Worsening headache

examination of the head, neck, and jaw.8 Any abnormal findings should be documented and compared with baseline examination findings if possible. Any new red flag findings, or symptoms that have progressed since a previous normal workup, should prompt additional assessment or consultation with an appropriate subspecialist (Table 5).8 There are no specific laboratory tests designed to diagnose persistent MTBI. Basic laboratory testing includes a complete blood count and thyroidstimulating hormone and electrolyte levels. Many imaging modalities are not applicable to the workup of subacute to chronic MTBI, although computed tomography and magnetic resonance imaging of the brain may be used in the setting of advancing or new red flag symptoms (Table 5).8 If cognitive symptoms persist or become disabling, formal neuropsychologic testing should be considered for further clarification.8,15 Neuropsychologic testing helps reveal factors that could contribute to persistent distress and symptom reporting, including personality style, emotional distress, symptom exaggeration, and cognitive impairment. Testing assesses the patientâ&#x20AC;&#x2122;s

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memory, attention capacity, and visual and spatial coordination, as well as his or her ability to reason, solve problems, understand and express language, and plan and organize thoughts. Test results may augment a differential diagnosis, guide further referrals to subspecialists and rehabilitation, and distinguish true pathology from malingering (particularly in cases involving litigation or compensation).8 Testing can also be used to detect pathology in scenarios in which patients may be motivated to minimize symptoms, such as when desiring to return to work or athletics. Natural History Most persons who experience uncomplicated MTBI will recover within one to two weeks following injury.8,17,18 Neuropsychologic group test scores are generally no different between patients with MTBI and the control group by three months after injury.5,22 Female sex, older age, lack of social support, less education, and comorbid mental health disorders have been linked to poor outcomes following the injury.8,17,18,22 Treatment Limited evidence exists for the management of MTBI; as such, the focus of treatment is on early education, managing specific symptoms, and preventing complications8,23-26 (Tables 28 and 38). Following acute MTBI, early education pertaining to diagnosis, prognosis, and symptoms creates realistic expectations, reduces anxiety, and helps normalize symptoms.8,24,25 Such reassurance has been shown to reduce symptom reporting in adults and children at three and six months after the injury.24 Effective interventions can include a single educational session and handout.24 Initially, patients should be counseled about physical and cognitive rest, followed by a gradual return to


American Family Physician normal activities.8 Patients should be monitored during recovery and encouraged to avoid overexertion while increasing work, school, and other activities as tolerated, because symptoms occasionally worsen or reappear.8 In most cases, this is the only intervention needed, and complete recovery will be achieved in days or weeks. Beyond early education and support, treatment of persistent symptoms of MTBI is undertaken without the benefit of research-based guidelines or therapies.25-27 In persons with chronic or severe MTBI sequelae, it becomes increasingly important to identify and address comorbidities or secondary problems that mimic the symptoms of MTBI or that complicate recovery, such as depression, chronic pain, or situational stress.15,28-30 Targeted treatment of persistent symptoms is recommended on a case-by-case basis.8 Behavioral treatments and pharmacologic management of sleep dysfunction, headache, fatigue, emotional disturbance, and cognitive difficulties may be undertaken with efforts to help the patient cope with stress and resume a more active life8,11 (Tables 28 and 38). Ultimately, a biopsychosocial approach is needed to understand and care for patients who have persistent symptoms. Referral to a specialized multidisciplinary clinic may be warranted in some instances.8 The term neurorehabilitation has emerged to represent a comprehensive multidisciplinary treatment approach that focuses on empowering each patient with his or her unique skills and attitudes to help overcome the injury, addressed in relation to each patient’s neurologic injury sequelae. Such multidisciplinary neurorehabilitative teams often include physicians; neuropsychologists; counselors; case managers; and speech, occupational, and physical therapists. Mental health treatment for persistent behavioral symptoms after MTBI (e.g., anxiety, depression or other mood disorders, sleep disorders, personality changes) should focus on the severity of individualized symptoms and comorbidities.8 Limited evidence suggests that cognitive behavioral therapy (CBT) is effective in the setting of acute stress disorder following MTBI.31 CBT, alone or combined with a comprehensive neurorehabilitation program, is well suited for the treatment of MTBI.31 It helps patients focus on developing effective coping behaviors, reducing stressors, and preventing relapse, and how to proactively address feelings of loss associated with decreased cognitive and physical functioning.31 CBT can also be structured to address impairments in memory, attention, and problem solving.31

Quality Improvement and Prevention The optimal treatment for MTBI is prevention of the initial injury. The Centers for Disease Control and Prevention has an online resource that provides information for physicians, including educational materials for patients, schools, and workplaces on how to reduce head injuries and facilitate improved health outcomes at http://www.cdc.gov/concussion/HeadsUp/ physicians_ tool_kit.html. REFERENCES 1. Pertab JL, James KM, Bigler ED. Limitations of mild traumatic brain injury meta-analyses. Brain Inj. 2009;23(6):498-508. 2. Ruff RM, Iverson GL, Barth JT, Bush SS, Broshek DK; NAN Policy and Planning Committee. Recommendations for diagnosing a mild traumatic brain injury: a National Academy of Neuropsychlogy education paper. Arch Clin Neuropsychol. 2009;24(1):3-10. 3. Mild Traumatic Brain Injury Committee of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine. Definition of mild traumatic brain injury. J Head Trauma Rehabil. 1993;8(3):86-87. 4. Practice parameter: the management of concussion in sports (summary statement). Report of the Quality Standards Subcommittee. Neurology. 1997;48(3):581-585. 5. Holm L, Cassidy JD, Carroll LJ, Borg J; Neurotrauma Task Force on Mild Traumatic Brain Injury of the WHO Collaborating Centre. Summary of the WHO Collaborating Centre for Neurotrauma Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2005;37(3):137-141. 6. McCrory P, Meeuwisse W, Johnston K, et al. Consensus statement on concussion in sport – the Third International Conference on Concussion in Sport, held in Zurich, November 2008. Phys Sportsmed. 2009;37(2):141-159. 7. National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Atlanta, Ga.: Centers for Disease Control and Prevention; September 2003. http://www.cdc.gov/ncipc/pub-res/ mtbi/mtbireport.pdf. Accessed August 21, 2011. 8. U.S. Department of Veterans Affairs. VA/DoD clinical practice guideline for management of concussion/mild traumatic brain injury. Washington, DC: U.S. Department of Defense; April 2009. http://www.healthquality. va.gov/mtbi/ concussion_mtbi_full_1_0.pdf. Accessed August 21, 2011. 9. Coronado VG, Faul M, Xu L, Wald MM. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths, 2002–2006. Atlanta, Ga.: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010. http://www.cdc.gov/traumaticbraininjury/pdf/blue_ book.pdf. Accessed August 21, 2011.

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American Family Physician Control and Prevention. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. Ann Emerg Med. 2008;52(6):714-748.

10. Jotwani V, Harmon KG. Postconcussion syndrome in athletes. Curr Sports Med Rep. 2010;9(1):21-26. 11. Quinlan JD, Guaron MR, Deschere BR, Stephens MB. Care of the returning veteran. Am Fam Physician. 2010;82(1):43-49. 12. Finkelstein EA, Corso PS, Miller TR. The Incidence and Economic Burden of Injuries in the United States. New York, NY: Oxford University Press; 2006. 13. Jones E, Fear NT, Wessely S. Shell shock and mild traumatic brain injury: a historical review. Am J Psychiatry. 2007;164(11):1641-1645. 14. Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. soldiers returning from Iraq. N Engl J Med. 2008;358(5):453-463. 15. Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat. 2005;1(4):311-327. 16. Meares S, Shores EA, Taylor AJ, et al. Mild traumatic brain injury does not predict acute postconcussion syndrome. J Neurol Neurosurg Psychiatry. 2008;79(3):300-306. 17. Carroll LJ, Cassidy JD, Peloso PM, et al.; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehab Med. 2004;(43 suppl):84-105. 18. McCrea M, Iverson GL, McAllister TW, et al. An integrated review of recovery after mild traumatic brain injury (MTBI): implications for clinical management. Clin Neuropsychol. 2009;23(8):1368-1390. 19. Belanger HG, Kretzmer T, Vanderploeg RD, French LM. Symptom complaints following combat-related traumatic brain injury: relationship to traumatic brain injury severity and posttraumatic stress disorder. J Int Neuropsychol Soc. 2010;16(1):194-199. 20. Whiteside JW. Management of head and neck injuries by the sideline physician. Am Fam Physician. 2006;74(8):1357-1362. 21. Jagoda AS, Bazarian JJ, Bruns JJ Jr., et al.; American College of Emergency Physicians; Centers for Disease

22. McCrea M, Pitskin N, Barth J, et al. Official position of the military TBI task force on the role of neuropsychology and rehabilitation psychology in the evaluation, management, and research of military veterans with traumatic brain injury. Clin Neuropsychol. 2008;22(1):10-26. 23. Snell DL, Surgenor LJ, Hay-Smith EJ, Siegert RJ. A systematic review of psychological treatments for mild traumatic brain injury: an update on the evidence. J Clin Exp Neuropsychol. 2009;31(1):20-38. 24. Ponsford J. Rehabilitation interventions after mild head injury. Curr Opin Neurol. 2005;18(6):692-697. 25. Comper P, Bisschop SM, Carnide N, Tricco A. A systematic review of treatments for mild traumatic brain injury. Brain Inj. 2005;19(11):863-880. 26. Borg J, Holm L, Peloso PM, et al.; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Nonsurgical intervention and cost for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004;(43 suppl):76-83. 27. Ruff R. Two decades of advances in understanding of mild traumatic brain injury. J Head Trauma Rehabil. 2005;20(1):5-18. 28. Silver JM, McAllister TW, Arciniegas DB. Depression and cognitive complaints following mild traumatic brain injury. Am J Psychiatry. 2009;166(6):653-661. 29. Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury: a systematic review. JAMA. 2008;300(6):711-719. 30. Gironda RJ, Clark ME, Ruff RL, et al. Traumatic brain injury, polytrauma, and pain: challenges and treatment strategies for the polytrauma rehabilitation. Rehabil Psychol. 2009;54(3):247-258. 31. Soo C, Tate R. Psychological treatment for anxiety in people with traumatic brain injury. Cochrane Database Syst Rev. 2007;(3):CD005239.

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American Family Physician

Practice Guidelines AACE Releases Guidelines for Menopausal Hormone Therapy

Table 1. U.S. Food and Drug Administration Contraindications to Menopausal Hormone Therapy

Menopause is diagnosed in women who have not had menses for one year. After menopause, up to 85 percent of women have symptoms such as hot flashes, sweating, insomnia, and vaginal dryness and discomfort. Although most symptoms resolve spontaneously after about five years, symptoms continue in a substantial number of women. Menopausal hormone therapy is the most effective treatment for these symptoms. The goal of this therapy is to improve quality of life, but possible risks must be weighed against the benefits of therapy. Chronic disorders are associated with aging and menopause. The role of menopausal hormone therapy in the prevention of these conditions is controversial.

Active liver disease

The American Association of Clinical Endocrinologists (AACE) convened a task force to review available evidence on therapies for menopausal symptoms. The task forceâ&#x20AC;&#x2122;s guidelines include recommendations for prescribing menopausal hormone therapies, and for weighing the risks and benefits in individual patients.

Untreated hypertension

Indications and Contraindications for Menopausal Hormone Therapy Menopausal hormone therapy is prescribed in the perimenopausal period or during early menopause based on an individual patientâ&#x20AC;&#x2122;s benefit-versus-risk profile. The U.S. Food and Drug Administration (FDA) has approved menopausal hormone therapy for moderate to severe vasomotor symptoms and moderate to severe vulvar and vaginal atrophy. Women who have had a hysterectomy should receive estrogen alone, and women with an intact uterus should receive estrogen plus a progestational agent to lower the risk of hyperplasia and endometrial cancer. Table 1 lists FDA contraindications for menopausal hormone therapy. Therapeutic trials of prescription nonhormonal alternatives may be considered for the treatment of menopausal symptoms with no contraindications. However, over-the-counter supplements should be used with caution because

Source: Adapted from Am Fam Physician. 2012;86(9):864-868.

Active or recent arterial thromboembolic disease (angina, myocardial infarction) Current, past, or suspected breast cancer Known hypersensitivity to the active substance of the therapy or to any of the excipients Known or suspected estrogen-sensitive malignant conditions Porphyria cutanea tarda (absolute contraindication) Previous idiopathic or current venous thromboembolism (deep venous thrombosis, pulmonary embolism) Undiagnosed genital bleeding Untreated endometrial hyperplasia

they are not regulated by the FDA and may interact with other drugs. Table 2 lists alternatives to estrogen therapy for treating menopausal symptoms.

Treatments Estrogens The lowest dosage of estrogen therapy that provides bone protection or relief from symptoms should be used. A reduction in dosage should be considered as the patient ages. Common regimens include conjugated equine estrogen or synthesized conjugated estrogen (0.3 to 0.625 mg), micronized 17β-estradiol administered orally (0.5 to 1 mg) or intramuscularly, transdermal estradiol (25 to 100 mcg), ethinyl estradiol (0.01 to 0.02 mg), topical estradiol preparations, and vaginal estrogenic preparations (vaginal estradiol ring, conjugated equine estrogen cream, estradiol cream). There are few differences among the treatment methods, although the oral and transdermal routes are most commonly used. The choice of estrogen should be based on patient preference and prior experience. However, the transdermal route is recommended for certain clinical situations, such as in women with hypertension, hypertriglyceridemia, and an increased risk of cholelithiasis, and possibly to reduce the risk of

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American Family Physician Table 2. Alternatives to Estrogen for Treating Menopausal Vasomotor Symptoms Centrally acting alpha-adrenergic blocking agents Oral clonidine, 0.1 mg daily Transdermal clonidine, weekly patch equivalent to 0.1 mg daily Gabapentin, 900 mg daily in divided doses Lifestyle modifications Relaxation techniques Use of fans, air-conditioning, and light clothing for hot flashes Phytoestrogens* Black cohosh, 40 mg orally daily Soy Progestational agents Intramuscular medroxyprogesterone, 500 mg every two weeks Oral medroxyprogesterone, 20 mg daily or 100 mg twice daily Oral megestrol, 20 mg twice daily Transdermal progesterone, 20 or 32 mg daily Selective serotonin reuptake inhibitors

include medroxyprogesterone (2.5 mg daily or 5 mg for 10 to 12 days per month), micronized progesterone (100 mg daily or 200 mg for 10 to 12 days per month), norethindrone (0.35 mg daily or 5 mg for 10 to 12 days per month), drospirenone (3 mg daily), and levonorgestrel (0.075 mg daily). Combination medications with estradiol and a progestational agent are available. Switching among different types of progestational agents may decrease possible adverse effects. Bioidentical Hormone Therapy Compounded bioidentical hormone therapies are claimed to be identical in structure to human hormones. However, in many cases, this has not been biochemically substantiated, and the compounded therapies are not regulated by the FDA. Although some FDA-approved bioidentical hormone preparations may be considered for menopausal symptoms, there is little evidence that they are safer or more effective than traditional menopausal hormone therapy.

Analysis of Benefits vs. Risks

Oral fluoxetine, 20 mg daily

Cancer

Oral paroxetine, 12.5 to 25 mg daily

Unopposed estrogen therapy has been associated with the development of endometrial cancer, and therefore a progestational agent should be added to prevent hyperplasia and endometrial cancer. Although data are conflicting, physicians should discuss with patients the possible relationship between menopausal hormone therapy and breast cancer. Evidence suggests that this potential relationship is stronger with estrogen/ progestational agent combinations than with estrogen alone. Using micronized progesterone rather than medroxyprogesterone and avoiding combined continuous therapy may be associated with a lower risk. Although study results regarding the effect of menopausal hormone therapy on the risk of ovarian cancer have been inconsistent, women should be advised that there is a possible increase in ovarian epithelial tumors after more than 10 years of therapy. Studies have demonstrated a decrease in the incidence of colon cancer and related mortality in women taking menopausal hormone therapy.

Oral venlafaxine, 75 mg daily Veralipride (not available in the United States) Vitamin E, 400 IU orally twice daily Note: Estrogen is the only therapy approved by the U.S. Food and Drug Administration for the treatment of menopausal symptoms. *Because phytoestrogens may have estrogenic effects, women with a personal or family history of hormone-dependent cancers, thromboembolic events, or cardiovascular events should not use soy-based therapies.

thromboembolic disease. Transvaginal estrogen may be considered to provide topical effects with less systemic absorption. Progestational Agents If a progestational agent is used in conjunction with estrogen, it should be taken a minimum of 10 to 14 days per month. Although amenorrhea may be achieved with daily use of a low-dose progestational agent, it is not recommended because recent studies have shown adverse breast outcomes with continuous therapy. Long-cycle use of progestational agents (14 days every three months) may be considered to reduce breast exposure, although the evidence is lacking. Common choices of progestational agents

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Venous Thromboembolic Disease Estrogen therapy has been associated with an increased risk of venous thromboembolic disease within one to two years of initiation. Women at increased risk of disease should not take estrogen-containing therapy, although recent research suggests that transdermal


American Family Physician estrogen may be safe. Aggressive smoking cessation is recommended for smokers who are considering menopausal hormone therapy because smoking increases the risk of venous thromboembolic disease in those who are taking estrogen. Stroke Some evidence shows that women on menopausal hormone therapy have more strokes, especially older women. Osteoporosis Menopausal hormone therapy should be used to prevent and treat osteoporosis when appropriate, after considering the risks versus benefits in the individual patient. Although nonhormonal therapies are available, randomized controlled trials have substantiated the

benefits of estrogen in preserving bone mass and, less consistently, in preventing fractures. Dementia Menopausal hormone therapy has not been shown to affect the risk of dementia and is not recommended to prevent or treat the condition. Cardiovascular Disease Menopausal hormone therapy should not be used in the primary or secondary prevention of cardiovascular disease. Lipid profiles, smoking history, and diabetes mellitus history should be considered before initiating therapy to determine individual cardiovascular risk. Smoking cessation is strongly advised for smokers who are considering menopausal hormone therapy because smoking increases the risk of cardiovascular disease in those who are taking estrogen.

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American Family Physician

Photo Quiz

Erythematous Papules on the Face A 19-year-old woman presented with a red rash on her face. The nonpainful bumps had been present for several years and had been unsuccessfully treated with topical retinoids and laser therapy. The patient had a history of seizure disorder and mental retardation. The examination revealed multiple erythematous papules coalescing into plaques around the buccal area of the patientâ&#x20AC;&#x2122;s face (see accompanying figure). She had mild erythema on her cheeks, forehead, and nasolabial folds. Her face was not warm to palpation, and she did not have open or closed comedones. A 3-mm punch biopsy of the erythematous area showed proliferation of fibrous tissue and perifollicular concentric fibrosis.

Question Based on the patientâ&#x20AC;&#x2122;s history, physical examination, and histologic features, which one of the following is the most likely diagnosis? A. Acne rosacea.

C. Systemic lupus erythematosus.

B. Neurofibromatosis.

D. Tuberous sclerosis complex. See the following page for discussion.

Source: Adapted from Am Fam Physician. 2012;86(11):1065-1067.

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American Family Physician Summary Table Condition Acne rosacea

Characteristics Chronic acneiform disorder of the facial pilosebaceous units; initial flushing and telangiectasias develop into papules, pustules, more persistent erythema, and fibrosis with edema; may affect the cheeks, nose, forehead, and chin; commonly triggered by heat, spicy foods, and alcohol

Neurofibromatosis

Autosomal dominant condition that is divided into two distinct disorders and affecting several systems; hyperpigmented macules or cafĂŠ-au-lait spots, with later development of diffuse pedunculated neurofibromas and central nervous system tumors Multisystem, autoimmune disorder characterized by erythematous, papular lesions in a buccal pattern; laboratory tests are typically positive for antinuclear antibodies, anemia, and elevated erythrocyte sedimentation rate; more common in young women Genetic condition characterized by nonmalignant growths in multiple organ systems; new-onset seizures are common in patients younger than 10 years, and seizures with facial angiofibromas are common in older patients

Systemic lupus erythematosus Tuberous sclerosis complex

Discussion The answer is D: tuberous sclerosis complex. Tuberous sclerosis complex is a genetic condition characterized by nonmalignant growths in multiple organ systems. Most patients with the condition will develop a hypopigmented macule or ash leaf spot on their skin, which can be 1 to 12 cm in size by one year of age. About 80 percent of patients will develop facial angiofibromas. By two years of age, 50 percent of patients will have a leathery skin-colored plaque (shagreen patch).1 The angiofibromas are composed of a dermal proliferation of fibroblasts arranged around hair follicles and blood vessels. Tuberous sclerosis complex occurs in approximately one or two in 10,000 live births.2,3 All of the clinical features of the disease may not be evident in the first two years of life. Newonset seizures are the most common presenting symptom in patients younger than 10 years, whereas seizures with facial angiofibromas are most common in older patients.4 The diagnostic criteria for tuberous sclerosis complex include several major and minor clinical features.5 This patient had three major criteria: facial angiofibromas, hypomelanotic macules, and a shagreen patch. Genetic testing may be used to confirm the diagnosis. No treatment is required for the angiofibromas because they are not precancerous. However, if treatment is desired for cosmetic reasons, dermabrasion and laser therapy may be effective. Treatment of the disease itself should involve a multidisciplinary team of family physicians, ophthalmologists, neurologists, and dermatologists. Neurologic complications from brain tumors and seizures are the most common cause of death from tuberous sclerosis complex, followed by renal disease.6 Despite treatment, 30 percent of patients with severe cases will die before five years of age, and up to 75 percent will die before reaching adulthood.7 Acne rosacea is a chronic acneiform disorder of the facial pilosebaceous units that is common in middle-aged adults. Rosacea usually starts with mild symptoms of flushing and telangiectasias that later develop into more persistent erythema, leading to papules, pustules, and eventually fibrosis with edema. The lesions can

affect the cheeks, nose, forehead, and chin.7 Common triggers include heat, spicy foods, and alcohol. Neurofibromatosis is a neurocutaneous autosomal dominant condition that is divided into two distinct disorders (neurofibromatosis 1 and 2) and affects several systems. In both conditions, patients develop hyperpigmented macules or cafĂŠ-au-lait spots during the first few years of life, and later develop diffuse pedunculated neurofibromas and central nervous system tumors. Bilateral acoustic neuromas are features of neurofibromatosis 2, whereas pigmented hamartomas of the iris (Lisch nodules) and pheochromocytomas are features of neurofibromatosis.1 Diagnosis is based on clinical criteria and a family history of the condition.7 Systemic lupus erythematosus is a multisystem, autoimmune disorder characterized by erythematous, papular lesions in a buccal pattern. It often affects young women, who are usually diagnosed in their 30s or 40s. The clinical course varies significantly. Laboratory tests may be positive for antinuclear antibodies (e.g., anti-dsDNA antibodies), anemia, and an elevated erythrocyte sedimentation rate. REFERENCES 1. Bolognia J, Jorizzo JL, Rapini RP, et al. Dermatology. 2nd ed. St. Louis, Mo.: Mosby/Elsevier; 2008. 2. Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:125-127. 3. Levy M, Feingold J. Estimating prevalence in single-gene kidney diseases progressing to renal failure. Kidney Int. 2000;58(3):925-943. 4. Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics. 2011;127(1):e117-e125. 5. Tuberous Sclerosis Alliance. Revised diagnostic criteria for tuberous sclerosis complex. http://www.tsalliance.org pages. aspx?content=54. Accessed August 14, 2012. 6. Shepherd CW, Gomez MR, Lie JT, Crowson CS. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991;66(8):792-796. 7. Wolff K, Johnson RA, Fitzpatrick TB. Fitzpatrickâ&#x20AC;&#x2122;s Color Atlas and Synopsis of Clinical Dermatology. 6th ed. New York, NY: McGraw-Hill Medical; 2009.

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cardiology

Study of Association Between Metabolic Syndrome and Acute Coronary Syndrome Virendra Dhakhada*, Madhu Panjwani**, Ajay Dabhi**

Abstract Aims: To ascertain the prevalence of metabolic syndrome (MetS) in patients with acute coronary syndrome (ACS) to study the impact of MetS on hospital outcomes and to find out association of each components of MetS with ACS. Study design: Hospital-based prospective cross-sectional study. Method: The study was conducted in 100 patients of ACS (ST-elevation MI [STEMI], non-STEMI, unstable angina) admitted in Sir Takhtsinhji Hospital, Bhavnagar. Patients having MetS were identified according to International Diabetes Federation (IDF) criteria. After detailed clinical evaluation and relevant investigations, correlation between MetS and ACS was explored. Results: Prevalence of MetS was 59% in ACS patients. Prevalence was higher in males (59.7%) compared to females (57.14%). Maximum numbers of patients with MetS were in age of 51-60 years. Among all parameters of MetS, positive predictive value was highest for high blood pressure (BP) followed by triglyceride (TG) level, fasting blood sugar (FBS), respectively. Conclusion: Prevalence of MetS was found more often after the age of 40 years more often commonly in males. High BP was found as a most prevalent parameter in the criteria for MetS.

Keywords: Metabolic syndrome, acute coronary syndrome

S

ince, the introduction of the concept of metabolic syndrome (MetS), a relatively enormous amount of new information has evolved relevant to the role of insulin resistance in human disease. Abnormalities related to insulin resistance have broadened considerably and the adverse clinical outcomes extend beyond type 2 diabetes and cardiovascular disease (CVD). The MetS is a cluster of metabolic abnormalities that includes insulin resistance, dyslipidemia, hypertension, a proinflammatory state and excess weight, particularly abdominal adiposity. Individuals with MetS are at increased risk for diabetes and CVD and at increased risk of mortality from CVD.1 Because inflammatory and thrombotic tendencies are part of this syndrome, the clinical outcome of foremost significance is atherosclerotic CVD.2 Adult Treatment Panel III (ATP III) of National Cholesterol Education Program (NCEP) recognized the importance of CVD risk factors of what they

*Senior Resident **Associate Professor, Dept. of Medicine Medical College and Sir Takhtsinhji Hospital, Bhavnagar, Gujarat Address for correspondence Dr Virendra Dhakhada Plot No.: 385/244, Shyam Vandana Sagwadi, Kaliyabid, Bhavnagar - 364 001, Gujarat E-mail: virendradhakhada@yahoo.com

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referred to as a “constellation of lipid and nonlipid risk factors of metabolic origin”, designated this cluster as the MetS and stated, “This syndrome is closely related to insulin resistance.”3 The primary goal of the ATP III in establishing criteria for making the diagnosis of the MetS is to identify individuals at increased CVD risk and initiate lifestyle changes to decrease this risk. Though both ATP III and International Diabetes Federation (IDF) have almost similar criteria for diagnosis of MetS, IDF criteria differ from ATP III in waist circumference, which is an essential criteria in IDF and also cut-off limit for waist circumference is different in different races. Material and Methods A cross-sectional study was carried out in 100 patients of ACS (ST-elevation myocardial infarction [STEMI], nonST-segment elevation MI [NSTEMI], unstable angina) admitted in Sir Takhtsinhji Hospital, Bhavnagar during the year 2010-2011. IDF criteria were used for diagnosis of MetS among these all patients. The IDF criteria for diagnosing MetS are described in Table 1.4 A detailed medical history of the patients including symptomatology, details of past illnesses, occupation, illnesses in the family, any particular habits and other morbid illness obtained. Complete physical examination and systemic examination were performed.


cardiology Table 1. IDF Criteria for Central Adiposity4

Table 2. Prevalence of MetS According to Gender

Waist circumference

Presentation

Men

Women

Ethnicity

≥94 cm

≥80 cm

Europid, Sub-Saharan African, Eastern and Middle Eastern

≥90 cm

≥80 cm

South Asian, Chinese and ethnic South and Central American

≥85 cm

≥90 cm

Japanese

Two or more of the following: zz

zz

zz

BP >130 systolic or >85 mm diastolic or previous diagnosis or specific medication Fasting plasma glucose ≥100 mg/dl or previously diagnosed type 2 diabetes

Each patient’s anthropometrical measurements were obtained with emphasis on measurement of height, weight, waist circumference, hip circumference, body mass index (BMI). Waist circumference was measured as per National Health and Nutrition Examination Survey (NHANES) protocol: In upright position, the right iliac crest of the patient was palpated and a horizontal mark was drawn just above the lateral border of it. It was crossed with a vertical mark in the midaxillary line. The measuring tape was placed around the abdomen at this level parallel to the floor and waist circumference was measured at normal minimal inspiration without compressing skin. Patients were diagnosed as having acute coronary syndrome (ACS)-based on ECG and cardiac biomarkers. Routine investigations including complete blood count, urine examination, renal function test, random blood sugar level were done along with fasting blood sugar, lipid profile and chest X-ray. Echocardiography, ultrasonography, CT head were done as and when required. After history and complete examination and investigations, correlation between MetS and ACS were studied. Data was entered and analyzed in SPSS software. Results Patients were divided in two groups: MS group: MetS with ACS; NMS group: ACS only without MetS. In our study, we found 59% prevalence of MetS in ACS patients. Prevalence was higher in males (59.7%)

Total

%

No

%

No/%

ACS only (NMS)

29

40.27

12

42.85

41

ACS + MetS (MS)

43

59.7

16

57.14

59

Total

72

100

28

100

100

Table 3. Clinical Characteristics in Study Groups Characteristics

MS group

NMS group

ACS + MetS (n = 59)

ACS without MetS, (n = 41)

56.76 (mean)

57.61 (mean)

Male

43

29

Female

16

12

Tobacco

19

17

NS

Smoking

30

18

NS

Alcohol

05

01

NS

Sedentary lifestyle

41

21

NS

STEMI

35

27

NS

Non-STEMI

15

06

NS

Unstable angina

09

08

NS

Waist circumference

59

33

p < 0.05

High BP

39

07

p < 0.05

Fasting TGs >150 mg/dl or specific medication HDL cholesterol <40 mg/dl and <50 mg/dl for men and women, respectively or specific medication

Female

No

Age (years)

p value

NS

Sex NS

Presentation

Components of MetS

High TG

39

10

p < 0.05

Elevated FBS

58

33

p < 0.05

Low HDL

31

17

NS

Mortality

02

01

NS

Number of patients

zz

Male

20 15 10

MS

5

NMS

0 <40 41-50 51-60 61-70 >71 Age group (years)

Figure 1. Age distribution.

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cardiology

70 Number of patients

60

59

58

50 40

33

39

39

33

30

17

20

10

7

10 0

31

Waist circumference

High blood pressure

Triglyceride

Fasting blood sugar

MS NMS

High-density lipoprotein

Figure 2. Prevalence of each component of MetS.

compared to females (57.14%) (Table 2). The maximum numbers of patients were in 51-60 years of age (Fig. 1). The prevalence of each component of MetS is shown in Figure 2. Clinical characteristics in both groups are described in Table 3. Among all parameters, positive predictive value was highest for high blood pressure (BP) followed by triglycerides (TG) and fasting blood sugar (FBS). As waist circumference is an essential IDF criteria for MetS, positive predictive value could not be obtained. Discussion Although NCEP-ATP III criteria is widely used in studies related with MetS, we have used IDF criteria mainly because looking at Asian phenotype of obesity, we could underestimate many patients with MetS by applying ATP III criteria. Analysis of data from the Framingham Heart Study and Bogalusa Heart Study also suggested that increase in central fat antedates the development of coronary heart disease, atherosclerosis and related disorders.5 Ramachandran et al6 have also modified ATP III guideline in urban Asian adults with use of modified waist circumference appropriate for Indian population (male >90 cm, female >80 cm). Three meta-analyses found that the MetS increases the risk for incident coronary artery disease (CAD).7-9 In our study, most patients of ACS who had MetS were >40 years and maximum were in age group of 51-60 years. The Jaipur Heart Watch study10 and third NHANES study11 show similar results. Prevalence of MetS was higher in males (59.7%) as compared to females (57.14%), which is similar with study done by Gandhi et al.12 Study done by Gupta et al13 and Ramachandran et al6 showed higher prevalence of

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MetS in females. The higher prevalence in our study may be due to other coronary risk factors in males as we have selected all patients of ACS for this study. In both the study groups, regarding the components of MetS, difference in waist circumference, high BP, TG and FBS was statistically significant with p < 0.05. In our study, we found highest positive predictive value for high BP followed by serum TG and FBS. The common presentation of ACS in both these groups was STEMI (59.32% in MS group and 65.85% in NMS group). The observed difference in mortality in both groups was statistically found to be insignificant though this could have been due to small sample size, which is similar to finding in study done by Pandey et al.14 Primary prevention of MetS through weight management and lifestyle modification will help us in preventing global burden of CVDs. References 1. Braunwaldâ&#x20AC;&#x2122;s Heart Disease: A Textbook of Cardiovascular Medicine. 8th edition, Libby, Bonow, Mann, Zipes (Eds.), Saunders, 2007. 2. Contemporary Diagnosis and Management of the Metabolic Syndrome. 1st edition, Grundy SM (Ed.), Handbooks in Health Care Company 2005:p.13. 3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-97. 4. Harrisonâ&#x20AC;&#x2122;s Principles of Internal Medicine. Fauci, Braunwald, Kasper, Hauser, Longo, Jameson, Loscalzo (Eds.), 17th edition, McGraw-Hill, 2008.


cardiology 5. Burke GL, Webber LS, Srinivasan SR, Radhakrishnamurthy B, Freedman DS, Berenson GS. Fasting plasma glucose and insulin levels and their relationship to cardiovascular risk factors in children: Bogalusa Heart Study. Metabolism 1986;35(5):441-6. 6. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome in urban Asian Indian adults - a population study using modified ATP III criteria. Diabetes Res Clin Pract 2003;60(3):199-204. 7. Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 2005;28(7):1769-78. 8. Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006;119(10):812-9. 9. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49(4):403-14.

10. Gupta R, Sarna M, Thanvi J, Rastogi P, Kaul V, Gupta VP. High prevalence of multiple coronary risk factors in Punjabi Bhatia community: Jaipur Heart Watch-3. Indian Heart J 2004;56(6):646-52. 11. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003;163(4):427-36. 12. Gandhi AU, et al. Study of patients with metabolic syndrome and its association with end-organ damage. Ind J Clin Prac 2011;22(6). 13. Gupta A, Gupta R, Sarna M, Rastogi S, Gupta VP, Kothari K. Prevalence of diabetes, impaired fasting glucose and insulin resistance syndrome in an urban Indian population. Diabetes Res Clin Pract 2003;61(1): 69-76. 14. Pandey S, Baral N, Majhi S, Acharya P, Karki P, Shrestha S, et al. Prevalence of the metabolic syndrome in acute myocardial infarction and its impact on hospital outcomes. Int J Diabetes Dev Ctries 2009;29(2):52-5.

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Antihypertensive and Cardioprotective Effects of Pumpkin Seed Oil ÂÂ

Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy.

ÂÂ

The pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO. (El-Mosallamy AE, Sleem AA, Abdel-Salam OM, et al. J Med Food 2012;15(2): 180-9).

ÂÂ

Telfairia occidentalis (fluted pumpkin) is one of the commonly consumed leafy vegetables in Nigeria. In a study on rats supplemented diets containing 3% and 6%, T. occidentalis decreased plasma and PMF cholesterol levels by 20% and 30% and by 30% and 45%, respectively. (Adaramoye OA, Achem J, Akintayo OO, et al. Hypolipidemic effect of Telfairia occidentalis (fluted pumpkin) in rats fed a cholesterol–rich diet. J Med Food 2007;10(2):330-6).

ÂÂ

Natural products like pumpkin seed oil may modify the potency of the calcium antagonist felodipine (FEL) or angiotensin-converting enzyme inhibitor (ACEI), captopril in modulating the biochemical derangement in blood, heart and kidney as well as blood pressure and heart rate of spontaneously hypertensive rats. (Zuhair HA, Abd El-Fattah AA, El-Sayed MI. Pharmacol Res. 2000;41(5):555-63.)

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Padma Shri & Dr BC Roy National Awardee

Dr SM Rajendran


Dentistry

Endodontic Management of Cutaneously Draining Odontogenic Sinus using Shoe Lace Technique Sumit Mohan

Abstract Odontogenic cutaneous sinus tract is a rare but well-documented condition. It is usually misdiagnosed as a local skin lesion and maltreated by systemic antibiotics and/or surgical intervention. This is because the primary etiology is incorrectly determined. We came across a 30-year-old patient who presented with a cutaneous lesion of dental etiology in the submental region with frequent purulent discharge which was not responding to systemic antibiotics. The case history, diagnosis and management of this condition using surgical endodontics are presented here.

Keywords: Cutaneous, odontogenic, endodontic surgery, shoe lace

A

n annotated glossary of terms in endodontics defines sinus tract as a tract leading from an enclosed area of inflammation to an epithelial surface. Odontogenic cutaneous sinus tract is a rare but well-documented condition. Specific dental symptoms are usually absent in such cases, patients typically first visit a physician for evaluation and treatment. These sinus tracts most commonly are found on the chin or in the submandibular area. However, all chronic draining sinus tracts of the face or neck should signal the need for thorough dental evaluation.1 When an acute periapical abscess forms, it drains along a path of least resistance. The odontogenic abscess may spread to deeper tissues causing fascial space infection or it may establish an intraoral or extraoral drainage in the form of a sinus tract. Intraoral or extraoral sinustract opening depends on the location of the perforation in the cortical plate by the inflammatory process and its relationship to facial-muscle attachments. After formation of a sinus tract, the inflammation at the apex of the root may persist for a long period of time because of the drainage through the sinus tract, a chronic abscess can remain asymptomatic for extended periods of time. If there is a closure of the sinus tract, then the chronic abscess may become symptomatic.2 Egress of the irritants from infected root canals into periradicular tissues can initiate formation and perpetuation of Senior Lecturer, Dept. of Conservative Dentistry and Endodontics Institute of Dental Sciences, Bareilly, Uttar Pradesh Address for correspondence Dr Sumit Mohan Senior Lecturer, Dept. of Conservative Dentistry and Endodontics Institute of Dental Sciences, Opp. Suresh Sharma Nagar, Bareilly, Uttar Pradesh E-mail: samsharma770@gmail.com

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periradicular lesions. Depending on the nature and quantity of these irritants, as well as duration of exposure of periradicular tissues, a variety of tissue changes can occur. Mild-to-moderate injuries of short duration cause reversible tissue damage and recovery of these tissues, whereas persistent and/or severe injuries usually result in irreversible changes in the pulp and development of periradicular lesions either in the form of granuloma, abscess or cysts. These infections will slowly tract through the cancellous bone following the path of least resistance and perforate the cortical plate to present either intra- or extraorally.3 Once pus has entered the soft tissue, its direction of spread is limited by muscles and facial planes, which tend to direct the pus towards certain defined areas, where it accumulates. If the apices of the teeth are above the maxillary muscle attachments and below the mandibular muscle attachments the spread of infection may be extraoral.4 Cutaneous lesion may develop over a long period of time, often distant from the site of primary infection. Hence, successful management of these odontogenic cutaneous sinus tracts of pulpal pathology depend on proper diagnosis. However, these lesions continue to be a diagnostic dilemma. A review of several reported cases reveal that patients have had multiple surgical excisions, radiotherapy, multiple biopsies and multiple antibiotic regimens, all of which have failed, with recurrence of the cutaneous sinus tract, as the primary etiology was dental that was never correctly diagnosed or addressed.1 The present case report discusses an extraoral sinus tract, which was cutaneous in nature, whose early and prompt diagnosis led to its timely treatment by surgical endodontic therapy.


Dentistry

Figure 4. Flap reflection. Figure 1. Pre-treatment photograph.

CASE REPORT A 30-year-old male patient reported to the Dept. of Conservative Dentistry and Endodontics with chief complaint of pus discharge around the submental region associated with mild pain since last two weeks. Detailed clinical examination revealed patient had grossly carious lower anterior tooth 31. He also presented with deep bite. Extraoral examination revealed a cutaneous sinus tract near the chin (Fig. 1). Radiographic examination revealed that tooth 31 was the cause (Fig. 2). Vitality of the adjacent teeth was checked using electric pulp tester and mandibular left central incisor was found to be nonvital.

Figure 2. Preoperative intraoral periapical radiograph.

Root canal treatment under rubber dam isolation of the involved tooth (Fig. 3 a and b) and management of the extraoral sinus tract was planned using â&#x20AC;&#x2DC;Shoe lace techniqueâ&#x20AC;&#x2122;. Shoe lace technique involved managing the sinus where a gauge piece soaked in chlorhexidine was inserted extraorally to disrupt the epithelium of sinus tract to make a patency for pus drainage. Under local anesthesia flap reflection was done (Fig. 4) and the root was exposed. The granulation tissue was removed using curettes (API). Shoe lace technique was performed to disrupt the epithelium of sinus tract (Fig. 5 a-c). The flap was repositioned and sutured using sling suture technique (Fig. 6). Patient reported asymptomatic at three months follow-up (Fig. 7). DISCUSSION

Figure 3 a and b. Endodontic therapy under isolation.

Cutaneous sinus tracts typically present as fixed, nontender, erythematous, nodulocystic lesions on the skin of the lower face. The patient is usually unable to recall an acute or painful onset and the lesion is seldom accompanied by symptoms in the oral cavity.5 Once, the infection from the offending tooth has perforated the

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Dentistry

Figure 6. Application of suture.

Figure 7. Three months follow-up.

periosteum, the tooth may become asymptomatic. Digital palpation of the involved area frequently reveals a ‘cord’ of tissue connecting the painless skin lesion to the involved maxilla or mandible. During palpation, an attempt should be made to ‘milk’ the sinus tract; production of a purulent discharge confirms the presence of a tract.6 Often, both the nodule and perilesional skin are slightly retracted below the level of the surrounding skin surface.7 The majority of dental sinus tracts develop intraorally. When an extraoral dental sinus tract occurs, it most often develops in close proximity to the offending tooth.8

Figure 5 a-c. Shoe lace technique.

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The cutaneous sinus tract of dental origin is an uncommon but well-documented condition in the medical, dental and dermatological literature.4 However, these lesions continue to be a diagnostic dilemma. The evaluation of a cutaneous sinus tract must


Dentistry begin with a thorough patient history and awareness that any cutaneous lesion of the face and neck could be of dental origin. Winstock9 described cutaneous lesions with dental infections. Kaban10 elaborated the path of spread of chronic dental infections. Approximately 80% of the reported cases are associated with mandibular teeth and 20% with maxillary teeth.11 Most commonly involved areas are the chin and submental region. The other uncommon locations are cheek, canine space, nasolabial fold, nostrils and inner canthus of eye.8 If the sinus tract is patent, a lacrimal probe or a gutta-percha cone can be used to trace its track from the cutaneous orifice to the point of origin, which is usually a nonvital tooth.12 The pattern of breakdown and repair of periradicular lesions was demonstrated by Fish. He described four reactive zones to the bacteria, which are zone of infection, contamination, irritation and zone of stimulation. The central infection zone consists of microorganisms and neutrophils, second contamination zone contains zone of round cell infiltrate. Irritation zone contains osteoclasts and macrophages and outer stimulation zone contains fibroblasts and forming collagen and bone. Egress of microorganisms into periradicular region causes tissue destruction in the central zone of infection. As the toxicity of irritants is reduced in central infection zone, the numbers of reparative cells increase in periphery. Removal of irritants, proper debridement and obturation permits reparative zone to move inward. The healing of periradicular tissues after root canal treatment is often associated with formation and organization of a fibrin clot, granulation tissue formation, maturation, subsidence of inflammation and finally restoration ofnormal architecture of periodontal ligament. Hence, treatment must be focused on elimination of the source of the infection.13,14 These patients are usually healthy. The sinus tract prevents swelling or pain from pressure build-up because it provides drainage of the odontogenic primary site.13 Thus, the draining sinus tract maintains a localized condition and prevents systemic involvement. Treatment involves making a patent pathway for the pus to drain. Many methods have been propagated, which range from periapically perforating the root of tooth during root canal treatment thus draining the pus through orthograde approach, to creating an extraoral pathway for providing rapid relief to the patient in case of large sinuses. Shoe lace technique is one such method, where the sinus is managed extraorally by inserting a gauge piece soaked in povidone iodine to make a path for pus drainage.3,4

CONCLUSION It may be concluded that the correct diagnosis is the key to treat sinus tracts. Successful management of odontogenic extraoral sinus tracts with pulpal pathology depends on proper diagnosis and removal of etiological factors by proper bio- and chemomechanical preparation and three-dimensional obturation. In such cases surgical management proves an adjunct for prompt and speedy management of the problem. Root canal treatment and endodontic surgery should be used judiciously to make a favorable environment, while effectively eliminating the pathogens and giving the body’s immune, healing and repair mechanism a chance to achieve the desired result thus sparing the patient from physical and psychological trauma. REFERENCES 1. Johnson BR, Remeikis NA, Van Cura JE. Diagnosis and treatment of cutaneous facial sinus tracts of dental origin. J Am Dent Assoc 1999;130(6):832-6. 2. Cohenca N, Karni S, Rotstein I. Extraoral sinus tract misdiagnosed as an endodontic lesion. J Endod 2003;29(12):841-3. 3. Ingle JI, Harold SC. Ingle’s Endodontics. 5th edition, BC Decker Inc, London. 4. Laskin DM. Anatomic considerations in diagnosis and treatment of odontogenic infections. J Am Dent Assoc 1964;69:308-16. 5. Tidwell E, Jenkins JD, Ellis CD, Hutson B, Cederberg RA. Cutaneous odontogenic sinus tract to the chin: a case report. Int Endod J 1997;30(5):352-5. 6. Valderhaug J. A histologic study of experimentally produced intra-oral odontogenic fistulae in monkeys. Int J Oral Surg 1973;2(2):54-61. 7. Calişkan MK, Sen BH, Ozinel MA. Treatment of extraoral sinus tracts from traumatized teeth with apical periodontitis. Endod Dent Traumatol 1995;11(3):115-20. 8. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol 1986;14(1):94-100. 9. Winstock D. Four cases of external facial sinuses of dental origin. Proc R Soc Med 1959;52:749-51. 10. Kaban LB. Draining skin lesions of dental origin: the path of spread of chronic odontogenic infection. Plast Reconstr Surg 1980;66(5):711-7. 11. Mittal N, Gupta P. Management of extra oral sinus cases: a clinical dilemma. J Endod 2004;30(7):541-7. 12. McWalter GM, Alexander JB, del Rio CE, Knott JW. Cutaneous sinus tracts of dental etiology. Oral Surg Oral Med Oral Pathol 1988;66(5):608-14. 13. Hodges TP, Cohen DA, Deck D. Odontogenic sinus tracts. Am Fam Physician 1989;40(1):113-6. 14. Cohen S, Burns R. Pathways of the pulp. 5th edition, Times Mirror/Mosby College Publishing, St. Louis

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Dermatology

Nevus of Ota is a Rare Nevus and Q-switched Laser is the Best Available Option for Successful Treatment OP Patidar*, Rekha Patidar**

Abstract Patients with the nevus of Ota have increased amounts of melanin (pigment) and melanin-producing cells (melanocytes) in and around their eyes. This includes the intraocular blood vessel layer called the uvea (choroid, ciliary body and iris), on the sclera (the white part of the eye ball), and in the eyelids. Q-switched laser is the best available option for successful treatment.

Keywords: Nevus of Ota, melanin (pigment), melanocytes (melanin-producing cells), Q-switched Nd-YAG laser

T

he nevus of Ota appears as increased pigmentation of one eye and its eyelids. The eyelid is darkened, pigment can be observed on the white of the eye and that iris may be darker (compared to the contralateral iris). Though none of these findings produce physical symptoms, physical asymmetry can have a psychological impact on the patient. Careful inspection of any patient with two different colored irises (heterochromia irides) may uncover the eyelid and episcleral pigmentation diagnostic of the nevus of Ota. Slit-lamp biomicroscopy is used to distinguish between conjunctival and episcleral pigmentation. Comparative examination of the irises can be used to evaluate coloration and surface characteristics. Dilated ophthalmoscopy similarly demonstrates asymmetric â&#x20AC;&#x2DC;darkerâ&#x20AC;&#x2122; pigmentation of the choroidal vascular layer beneath the retina. Ophthalmic ultrasound imaging will reveal the thickening of the vascular uveal layer of the eye.

*Assistant Professor Dept. of Medicine **Assistant Professor Dept. of General Surgery Jhalawar Medical College, Jhalawar, Rajasthan Address for correspondence Dr OP Patidar Gayatri Colony, NH-12 Jhalawar - 326 001, Rajasthan E-mail: dr.oppatidar.patidar@gmail.com

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Ocular melanosis has the same ocular melanocyte and pigment distribution as well as the risks associated with the nevus of Ota. But, in cases of ocular melanosis there is no eyelid involvement. Case Report A 22-year-old female student of dental college presented to us with complaints of dark bluish pigmentation over right upper one-third of face along with involvement of right eye. This pigmentation had been present since birth but initially in infantile age, it was a very small crescentic lesion just below the right eye with a very small wedge-shaped lesion in right eye. This lesion remained stationary for initial few years but with advancing age especially at the age of puberty, the lesion spread gradually and involved the right upper one-third of face including upper and lowers eyelids with involvement of right eye on examination. She is a healthy young girl, with dark bluish pigmentation over right upper one-third of face along with involvement of bulbar conjunctiva of right eye. No similar hypo- or hyperpigmentation was seen elsewhere on the body. She was diagnosed as a case of nevus of Ota. Hydroquinone preparation had been applied locally years together but there was no response. Ultimately laser therapy was decided upon. Q-switched Nd-YAG 1,064 laser was used and seven treatments were given with satisfactory results. Over 90% of pigment has disappeared from the affected site. Hydroquinone and sunscreen lotion are used daily.


Dermatology

Figure 1. Pre-treatment.

Figure 2. Post-treatment.

Figure 3. Pre-treatment.

Figure 4. Post-treatment.

Discussion

Nevus of Ota is more common in females; the ratio of male-to-female is 1:4.8. It has been observed that the onset is common at puberty in females so female sex hormones have been suggested as persistent stimuli.

Nevus of Ota is a form of congenital dermal melanosis, a rare entity in Indians and common in Japanese as compared to others, the incidence rate was about 0.4%.1 No exact incidence of nevus of Ota in Indians is available so far. Although there have been reports of nevus of Ota in three successive generation, most patient have no family history.2 The age of onset is another interesting aspect: It is not uncommon for nevus of Ota to appear in the perinatal period or around puberty. In one study, it was found that 48% developed the nevus at or soon after birth, 11% developed it between 1 and 10 years of age and the remaining 36% developed it between 11 and 20 years of age.3

Female sex hormones also have an important role in the development of other melanocytic conditions such as melasma; other stimuli, such as infection, trauma or ultraviolet light exposure have also been reported to trigger onset of the nevus.4-6 In this case also, similar is true as the lesion spread at puberty. Patients with the nevus of Ota are at greater risk for development of intraocular and central nervous system malignant melanomas (e.g., choroidal melanoma less than 4%). Patient with the nevus of Ota should be periodically examined by ophthalmologists and neurologists. As far

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Dermatology as treatment of nevus of Ota is concerned, laser therapy is the mode of choice because of excellent results in short duration but cost and availability are the limiting factors. Ideally Q-switched Nd-YAG laser is used and complete removal requires an average of eight treatments, spaced at least a month apart, using different wave lengths for different colored skin lesions. Q-switched lasers will shatter the pigment into particles that are cleared by the lymphatic system of the body. Q-switched laser is also used to remove tattoos. In this case only seven treatments were given spaced at least six months apart because of her education schedule. But results are satisfactory.

References 1. Rapini Ronald P, Bolognia Jean L, Jorizzo Joseph L. Dermatology. 2-Volume Set. Mosby: St. Louis 2007:p. 1720-2. 2. James William D, Berger Timothy G, et al. Andrews Diseases of the Skin: Clinical Dermatology. Elsevier: Saunders, 2006. 3. Chan HH, Kono T. Nevus of Ota: clinical aspects and management. Skinmed 2003;2(2):89-96; quiz 97-8. 4. eMedicine-Nevi of Ota and Ito. Article by Harvey Lui.

Acknowledgment

5. Geronemus RG. Q-switched ruby laser therapy of nevus of Ota. Arch Dermatol 1992;128(12):1618-22.

We are highly thankful to Dr Lakshyajit D Dhami, MS MCh (plastic) cosmetics, plastic and laser surgeon Hon. Nanavati Hospital, Mumbai, for laser treatment.

6. Shimbashi T, Hyakusoku H, Okinaga M. Treatment of nevus of Ota by Q-switched ruby laser. Aesthetic Plast Surg 1997;21(2):118-21.

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Mycophenolate mofetil is effective as a steroid-sparing agent in pyoderma gangrenosum, according to findings reported online July 15 in the Journal of the American Academy of Dermatology. The efficacy and safety of MMF was examined by Dr Jane Li and Dr Robert Kelly from St. Vincent’s Hospital Melbourne in Fitzroy, Australia by reviewing the charts of 26 patients with pyoderma gangrenosum, the largest series of such patients to date. (Source: Medscape) _________________________________________________________________________ Very few physicians mention sunscreen during patient visits, even when seeing patients with a history of skin cancer, according to a new study published online September 4 in JAMA Dermatology. In the study, there were no differences in sunscreen recommendation with respect to age or ethnicity; however, sunscreen was recommended more often for patients in their 70s and was recommended the least for children younger than 10 years.

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ENT

Papillary Thyroid Carcinoma Presented as Cystic Neck Mass: A Rare Presentation SANTOSH KUMAR PRATINIDHI*, SANJAY PANDA**, DILLIP DAS†

Abstract Cervical cystic mass is a rare presentation of papillary thyroid carcinoma. This cystic change can cause diagnostic problems and not infrequently, delay identification of the primary thyroid tumor. We present a rare case of cystic papillary thyroid carcinoma, which is presented as asymptomatic neck mass of long duration. Their clinical presentation, diagnosis and management were reviewed.

Keywords: Cyst, neck, papillary thyroid carcinoma

C

ystic neck masses appearing in the anterior or posterior triangles of the neck are usually benign. Papillary thyroid carcinoma is the most common thyroid malignancy, accounting for 80% of all thyroid cancers. The most common presentation of thyroid cancer is an asymptomatic thyroid mass or a nodule. A pure cystic nodule, although rare (<2% of all nodules), is highly unlikely to be malignant. This process may also occur in the metastatic lymph nodes, in which a subcortical liquefaction necrosis results in a cystic mass; this is more common in younger patients. This cystic change can cause diagnostic problems.

Case report A 70-year-old female patient was presented with swelling in front of the neck since two years with dysphagia since 3-month duration with dyspnea on exertion since one month. Initially, small in size, it started in thyroid region right side and gradually increased to present size (Fig. 1). On examination, there were multiple cystic swellings extending from thyroid cartilage to angle of mandible to supraclavicular triangle of same side involving both anterior and posterior triangle. It extends to anterior triangle of left side. There were about 10-12 *Consultant ENT Surgeon, Pratinidhi ENT Clinic, Cuttack, Odisha *Associate Professor, Dept. of Head and Neck Oncosurgery, Acharya Harihar Regional Cancer Centre, Cuttack, Odisha †Consultant Pathologist, Cuttack, Odisha Address for correspondence Dr Santosh Kumar Pratinidhi C/O: Y Diankar, Christian Street, Biju Patnaik Chhak, Cuttack - 753 008, Odisha E-mail: skpratinidhi@yahoo.com

Figure 1. Large swelling in right side of neck in the region of thyroid.

cysts with features of intercommunication. The whole swelling did not move with deglutition and there was no independent mobility of cysts. Cervical lymph nodes were not enlarged. On indirect laryngoscopy, right vocal cord was compromised and interglottic space was narrowed and right side pyriform fossa was compromised. Thyroid profile was within normal limits. Fine needle aspiration cytology (FNAC) of the swelling showed features suggestive of nodular goiter with cystic degeneration. Magnetic resonance imaging (MRI) of neck revealed a large heterogeneous mass lesion in the right side of neck inseparable from the right lobe of thyroid with encasement of the right internal carotid artery. There is an approximately 10.5 × 8.2 × 13.5 cm size multiloculated

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ENT

Figure 2. Specimen showing papillary structure with fibrovascular core in low magnification.

Figure 3. Specimen showing nucleus crowding, ground glass chromatin and nuclear grooving on high magnification.

solid and cystic lesion. It was showing iso- to hypointensity on T1W, heterogeneously hyperintensity on T2W sequence. Patient was subjected for surgery. Under general anesthesia use a collar incision was taken over the swelling and in middle, the incision was extended vertically upward upto the right ear lobe as T incision and flaps raised. Fluid in cyst was clear, light brown in color.

(39-90%) of patients having nodal involvement at presentation. These metastases are usually to the ipsilateral jugular chain (87.8%) and are usually confined to level III and IV (73.2%). Papillary thyroid carcinoma is a slowly growing neoplasm, which explains the relatively long duration of the neck masses.

Some cysts were intercommunicating and found arising from right lobe and isthmus of thyroid. On the right side cysts were adherent to internal jugular vein (IJV) and common carotid artery. IJV was ligated and divided. Cysts were separated from right carotid artery. Mass was found adhered to esophagus. Right hemithyroidectomy with modified radical neck dissection with partial esophagectomy was done. Esophagus and pharyngeal mucosa was repaired in straight-line closure around a Ryleâ&#x20AC;&#x2122;s tube. Wound was closed in layers with suction drain. Histopathological examination of specimen showed papillary structure with fibrovascular core in low magnification (Fig. 2). On high magnification nucleous crowding, ground glass chromatin and nuclear grooving was seen (Fig. 3). It was diagnosed to be papillary carcinoma of thyroid of classic type; infiltrating striated muscle bundles were also found. Patient underwent a radioactive iodine ablation postoperatively and is on suppressive dose of thyroxine since then. Discussion Papillary thyroid cancer typically occurs in the middle aged women in the 3rd and 4th decades (F:M ratio of 1:1.6-3:1). Papillary carcinoma has a tendency to metastasize early to local lymph nodes, with 50%

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Papillary thyroid carcinoma with extrathyroidal extension occurs in 4-16% (distal hematogeneous dissemination 5-10%) of cases and carries with it an increased risk of disease recurrence and death. Common extrathyroidal extension include involvement of recurrent laryngeal nerve, larynx, trachea, esophagus and skin with sinus formation is rare. Approximately 40% (reported range, 21-50%) of all lymph node metastases from papillary thyroid carcinomas have the tendency to completely cavitate a lymph node and thus may mimic an apparently benign cervical cyst. The origin of these cysts is controversial. Some authors think that it represents a malignant transformation of ectopic thyroid tissue. Others think that it represents a secondary metastatic spread from occult thyroid lesion to the lymph node, which underwent central liquefaction with cystic formation. FNAC is less sensitive in the diagnosis of cystic neck masses compared with solid masses having a false negative rate ranging from 50% to 67%. A study by Muller et al found that FNAC had false negative rate of 45% which was due to sampling error and not cytological misdiagnosis. Wunderbaldinger et al showed that in 80% of cystic nodes in papillary thyroid carcinoma the aspirated fluid was brownish viscous and had elevated thyroglobulin levels.


ENT Som et al and King et al hypothesized that high intranodal concentration of thyroglobulin reflect areas of high attenuation on computed tomography (CT) and inhomogeneous intracystic signal changes on MRI, respectively. Fluid from these cystic lesions should be sent for thyroglobulin analysis and thyroglobulin immunohistochemical staining may assist in the diagnosis of papillary thyroid carcinoma. Postoperative radioisotope scanning can identify remnants of thyroid tissue and metastasis. Adequate surgery by removing the cyst, all of the involved thyroid tissue and accessible involved lymph nodes is essential for better prognosis. Postoperative radioiodine ablation of thyroid remnant with suppressive thyroxine dose is advocated to reduce recurrences. Papillary thyroid carcinoma clinically behaves in an indolent fashion and carries an excellent prognosis, >90% survival at 20 years. Extrathyroid involvement has a (54%) 15-year survival and (29%) 30-year survival. Conclusion High index of suspicion should be adopted when managing unusual neck cysts located in unusual sites

in adults. Diagnostic thyroid ultrasound and neck CT or MRI scan may display the primary thyroid lesion. This would require total or hemithyroidectomy and modified radical neck dissection, followed by radioactive iodine ablation postoperatively with suppressive dose of thyroxine. Cystic papillary thyroid carcinomas not only cause diagnostic confusion but also produce delay in treatment and management. Clinical suspicion and meticulous intervention is the key for a better outcome. Suggested reading 1. Al-Ashaa Y, Hefny AF, Joshi S, Abu-Zidan FM. Papillary thyroid carcinoma presenting as a lateral neck cyst. Afr Health Sci 2011;11(2):296-300. 2. Patil VS, Vijayakumar A, Natikar N. Unusual presentation of cystic papillary thyroid carcinoma. Case Rep Endocrinol 2012;2012:732715. 3. Hervás Benito I, Rivas Sánchez A, Prieto Rodríguez M, Vera Sempere FJ, Saura Quiles A, Bello Arques P, et al. Simple thyroid cyst. Rev Esp Med Nucl 2001;20(1):32-5. 4. Andersen PE, Kinsella J, Loree TR, Shaha AR, Shah JP. Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 1995;170(5):467-70. 5. Aytug S, Sievert R, Ross FA. Occult papillary thyroid carcinoma presenting as extrathyroidal solitary neck cyst. QJM 2002;95(3):186-8.

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Therapeutic Algorithm Developed for Optimal Nosebleed Management Approximately 60% of people experience epistaxis, commonly known as nosebleed, at least once in their lifetime. Of those who experience nosebleed, six percent require medical treatment. A study in the September 2013 issue of Otolaryngology-Head and Neck Surgery, explores which nosebleed treatment options demonstrate the best outcomes. ‘Although data exist on the efficacy of the different epistaxis management techniques, outcome comparisons between the modalities for both primary management as well as management of cases of recurrence are currently lacking,’ the authors stated. The study analyzed various treatment outcomes of adult patients with epistaxis presenting to otolaryngologists at a tertiary care center between 2005 and 2011. The authors observed 147 patients (94 men and 53 women) who underwent cauterization, tamponade or nondissolvable packing, and/ or proximal vascular control through embolization or surgical ligation. Treatment outcomes were then compared with the intent to derive an algorithm for optimal nosebleed management. According to the study, nondissolvable packing demonstrated the highest rate of failure or recurrence (57.4%) for initial bleed management. Chemical cautery was significantly more successful in achieving lasting hemostasis for the first bleeding episode. The authors also found that the duration of the nondissolvable pack placement had no significant impact on nosebleed recurrence. Furthermore, among patients who failed initial management, those who next underwent more invasive procedures such as cautery, embolization or surgical ligation experienced better outcomes and shorter inpatient stays. Because the subgroup analyses were limited in size for some of the treatment groups in this study, the authors urge caution when considering these findings. Although most cases of nosebleed do not require medical intervention, those patients who do present to a tertiary care otolaryngologist and need medical attention require a systematic, stepwise approach to address their condition. This study demonstrates “good outcomes with initial treatment with chemical cautery and with procedures that achieve directed vascular control in patients who develop epistaxis recurrence.”

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ENT

Interval Tonsillectomy: 27 Cases of Peritonsillar Abscesses Managed in Medical College Hospital Sudhir M Naik*, Sarika S Naik**

Abstract Background and objectives: Peritonsillar abscess (quinsy) is the most common deep infection of the head and neck. The surgical treatment whether abscess tonsillectomy or interval tonsillectomy should be done is a subject of controversy, which still remains unresolved. Setting: Dept. of ENT, Head and Neck Surgery, KVG Medical College, Sullia, Karnataka. Material and methods: This was a comparative case series analysis study done in our department during the study period of 54 months from January 2007 to June 2011. Twenty-seven patients with clinical features of peritonsillar abscess who underwent medical line of treatment with incision and drainage and later interval tonsillectomy were included in the study. Results: The mean age was 30.4 years, mean hospital stay during incision and drainage was 3.51 days. The patient turned up for surgery within a mean duration of 9.4 months. The mean blood loss during the procedure was 100.5 ml and the mean visual analog scale (VAS) scores after interval tonsillectomy were 4.78. Mild-to-moderate difficulty was seen during the dissection of the abscess scarred tonsillar bed. Conclusion: Interval tonsillectomy is the standard treatment for managing peritonsillar abscess in many institutions. We recommend interval method of tonsillectomy done after a minimum of six weeks after incision and drainage of the peritonsillar abscess.

Keywords: Peritonsillar abscess, interval tonsillectomy, quinsy tonsillectomy, incision and drainage

P

eritonsillar abscess (quinsy) is the most common deep infection of the head and neck.1 It is seen commonly in young adults but now it is also seen frequently in older individuals.2,3 Incidence is higher in the age group 20-40 years adults.2,3 Children in the younger pediatric age group are seldom affected unless immunocompromised but if it occurs, it causes significant airway obstruction and morbidity.2,3 Males and females are equally affected.2,3 The incidence increases during the months of November to December and April to May because of highest incidence of streptococcal pharyngitis and exudative tonsillitis.4,5 This infection begins as a superficial tonsillar infection and progresses into tonsillar cellulitis forming an abscess at the most advanced stage.1 Abscess is always a polymicrobial infection, but Group A streptococcus is the predominate organism.1 Usually a combination of aerobic and anaerobic organisms are seen on culture.2 Early diagnosis and initiation of therapy is important to avoid

*Dept. of ENT, Head and Neck Surgery **Dept. of Anesthesia KVG Medical College, Sullia, Karnataka

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potential serious complications.6 Symptoms include progressively worsening sore throat with severe odynophagia, with difficulty to swallow his own saliva. Odynophagia is often localized to one side with constitutional symptoms of fever, malaise, dysphagia and otalgia.1 Clinically the tonsils look swollen, erythematous, edematous pillars with purulent exudates on the tonsils and contralateral uvular deviation.1 Trismus and a hot potato muffled voice with cervical lymphadenopathy are seen.1 Ultrasonography and computed tomography (CT) scanning are useful in confirming a diagnosis.1 Needle aspiration remains the gold standard for diagnosis and treatment of peritonsillar abscess.1 The management includes immediate abscess drainage and administering broad-spectrum antibiotic therapy for aerobes and anaerobes. Also electrolyte imbalance should be corrected and analgesics given for pain.1 Group A streptococcus and oral anaerobes sensitive antibiotics should be the first-line of therapy.7 Steroids may be helpful in reducing symptoms and speeding recovery.8 Here in our study, a series of 27 patients who underwent interval tonsillectomy six weeks after incision and drainage for peritonsillar abscess were retrospectively studied.


ENT Material and methods This was a comparative case series analysis study done in our department during the study period of 54 months from January 2007 to June 2011. Twenty-seven patients with clinical features of peritonsillar abscess who underwent medical line of treatment with incision and drainage were included in the study. All the 27 patients underwent interval tonsillectomy six weeks after incision and drainage. The age group ranged from 13 to 58 years and the youngest patient was a 13-year-old

Figure 1. Left sided peritonsillar abscess in a young boy being drained.

Figure 3. Left-sided peritonsillar abscess in a old man being drained.

male student (Figs. 1 and 2) and the oldest, a 58-yearold male farmer (Figs. 3 and 4). Tonsillectomies done for other indications were excluded from the study. Peritonsillar abscesses drained and those who did not turn up for surgery were excluded. All the abscesses drained were sent for culture and sensitivity. All the 27 cases were drained in the OPD with 15% lidocaine spray and St Clair Thompson peritonsillar abscess draining forceps. The abscess was redrained next two days till the abscess dried off.

Figure 2. Inflamed tonsillar tissue after abscess drainage.

Figure 4. Patient having relief after incision and drainage.

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ENT The patients who were having absolute dysphagia, unable to swallow their own saliva, had immediate symptomatic relief after the procedure. All the patients were discharged after the pain and swelling subsided. They were advised to undergo interval tonsillectomy after six weeks. The patients underwent tonsillectomies after a month in our institution with scalpel cautery method. Results Our study consisted of nine females and 18 males with a mean age of 30.4 years. Eight patients had right-sided abscess and 19 had left-sided. No bilateral case was seen in our study. The average stay in the hospital during incision and drainage was 3.51 days. The average time after incision and drainage that the patients turned up for interval tonsillectomy was 9.4 months. All the patients were operated under general anesthesia with endotracheal intubation. The degree of difficulty while dissecting the abscess scarred tonsil was graded as Grade 0 - no difficulty, Grade 1 - mild difficulty, Grade 2 - moderate difficulty, Grade 3 - severe difficulty. The average difficulty scores was 1.51 with score of 3 seen in only three patients. The average blood loss during the surgery was 100.5 ml. The pain scores were measured at 8, 16, 24 and 48 hours using 10 cm visual analog scale (VAS) and an average score of 4.78 was found. (Table 1). The blood loss and VAS score are as less as seen in tonsillectomies for chronic tonsillectomy cases and so we recommend interval tonsillectomy after six weeks after incision and drainage for peritonsillar abscess. Discussion

and finally to peritonsillar abscess.12 Early diagnosis, with drainage of the abscess, is crucial to prevent perforation into the parapharyngeal/retropharyngeal space and further spread along the neck vessels to the mediastinum and skull base.12 The abscess may be aspirated causing severe upper airway obstruction, epiglottic or laryngeal edema if the treatment is delayed.12 Although unilateral peritonsillar abscess is a common complication of acute bacterial tonsillitis, bilateral peritonsillar abscesses are quite rare.13 In most bilateral cases, an unsuspected contralateral abscess is discovered during tonsillectomy.13 The basic management strategy consists of systemic antibiotics covering Group A β-hemolytic streptococci, which is reported to be the most common offending organism and subsequent drainage of the pus.14 Abscess draining can be done by wide bore needle aspiration, or incision drainage or immediate tonsillectomy, which is called abscess, hot or quinsy tonsillectomy.15 The surgical treatment whether abscess or interval tonsillectomy should be done is a subject of controversy, which still remains unresolved.15 Immediate tonsillectomy is an easy to perform one-stage surgical procedure assuring quick relief of trismus and pain, and total evacuation of the pus.16 On the contrary, incision and drainage, which is also supported by many authors is an awkward procedure, very unpleasant for the patient that could often lead to incomplete evacuation of the abscess cavity.16 That is the reason why the procedure is often necessary to be repeated several times.16 Besides, if an interval tonsillectomy is planned, such an operation could be technically more difficult because of the fibrosis of the tonsillar bed usually developed.16

Peritonsillar abscess and peritonsillitis are two of the commonest ENT emergencies.9 They are collections of purulent material that develop outside the tonsillar capsule near the superior pole.9 They may develop as the most frequent complications of acute tonsillitis, when the infection spreads from the crypts to the loose areolar peritonsillar tissues.9 They are mainly situated in the upper pole and involve the soft palate pushing the tonsils forwards and towards the midline.9 The condition is usually unilateral and mostly affects young adults.10 Edinger et al in their study noted a male dominance upto 2:1 and higher number of young adults.10 Papacharalampous et al reported 1.6:1 times higher incidence in males in their 10-year series study and higher incidence in 20-40 years age group.11

On the other hand, initial conservative (nonsurgical treatment) is still supported by some authors in selected cases, before taking the risk of surgical drainage.17 This strategy is reported to be involved especially in cases of inferior pole peritonsillar abscess, provided that the patient is immunocompetent and has no significant systemic diseases.18 Kristensen and Tveteras in a retrospective study reported no significant difference in postoperative hemorrhages in quinsy tonsillectomy as well as interval tonsillectomy groups.19 Bonding et al found no significant difference in the rates of postoperative hemorrhage between quinsy tonsillectomy and routine tonsillectomy.20,21 Risks of general anesthesia are more in quinsy tonsillectomy as difficult intubation or aspiration due to abscess rupture may be seen during the procedure.22

It is believed to be a part of a clinical modality that progresses from acute tonsillitis to peritonsillar cellulitis

The overall incidence of quinsy in the adult population varies in different studies and a recurrence of peritonsillar

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ENT Table 1. Description of the Patients Treatment Records Sex

Age

Laterality

Duration of stay after I & D (days)

Interval tonsillectomy done after I & D (weeks)

Blood loss at interval tonsillectomy (ml)

Difficulty in dissection

Average VAS score for 48 hours post-op

M

13

L

4

6

110

1

5.3

M

23

L

3

5

60

1

4.6

M

29

L

5

8

55

2

4

F

32

L

3

12

100

1

4.6

F

36

L

4

11

150

2

5.3

M

58

L

2

12

180

3

6

M

54

R

4

5

60

2

5.3

M

43

R

5

6

60

2

5.3

M

45

L

3

12

80

3

6

F

32

L

2

10

80

1

4.6

F

25

L

3

12

60

1

5.3

M

18

R

4

14

70

1

4

M

19

R

5

12

80

1

4.6

F

37

L

2

10

70

1

4.6

M

18

L

2

9

70

2

5.3

M

20

R

3

9

80

1

4

M

23

L

3

8

100

2

4

F

22

L

4

8

110

2

5.3

M

24

R

4

12

150

2

5.3

F

22

L

5

12

110

1

4

M

18

L

5

11

110

1

4.6

M

22

R

3

6

120

1

4

F

23

L

3

8

90

1

4

M

23

L

4

8

90

3

6

M

52

R

3

9

100

1

4.6

M

44

L

3

8

180

1

4

F

46

L

4

11

190

1

4.6

3.51

9.40

100.55

1.51

4.78

Mean

30.40

abscess varies from 5% to 23% depending on the follow-up period.22 Herbild and Bonding reported a recurrence rate of 22% in 131 patients over a 5-year period.23 Savolainen et al reported a 17% recurrence rate in a prospective study of 98 patients over a 5-year period, while Raut et al reported a 8.5% recurrence rate.24

Conclusion Interval tonsillectomy is the standard treatment for managing peritonsillar abscess in many institutions. As quinsy tonsillectomy has no advantages over interval method, less risky interval method is recommended.

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ENT Quinsy tonsillectomy has disadvantages of aspiration and difficulty during anesthesia. We recommend interval method of tonsillectomy with surgery done after a minimum of six weeks after incision and drainage. References

12. 13.

1. Galioto NJ. Peritonsillar abscess. Am Fam Physician 2008;77(2):199-202. 2. Steyer TE. Peritonsillar abscess: diagnosis and treatment. Am Fam Physician 2002;65(1):93-6. Erratum in: Am Fam Physician 2002;66(1):30. 3. Khayr W, Taepke J. Management of peritonsillar abscess: needle aspiration versus incision and drainage versus tonsillectomy. Am J Ther 2005;12(4):344-50. 4. Belleza WG, Kalman S. Otolaryngologic emergencies in the outpatient setting. Med Clin North Am 2006;90(2):329-53. 5. Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. Clin Infect Dis 2002;35(2):113-25. 6. Herzon FS. Harris P. Mosher Award thesis. Peritonsillar abscess: incidence, current management practices, and a proposal for treatment guidelines. Laryngoscope 1995;105(8 Pt 3 Suppl 74):1-17. 7. Brook I. The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis. Int J Antimicrob Agents 2001;17(6):439-42. 8. Ozbek C, Aygenc E, Tuna EU, Selcuk A, Ozdem C. Use of steroids in the treatment of peritonsillar abscess. J Laryngol Otol 2004;118(6):439-42. 9. Richardson KA, Birck H. Peritonsillar abscess in the pediatric population. Otolaryngol Head Neck Surg 1981;89(6):907-9. 10. Edinger JT, Hilal EY, Dastur KJ. Bilateral peritonsillar abscesses: a challenging diagnosis. Ear Nose Throat J 2007;86(3):162-3. 11. Papacharalampous GX, Vlastarakos PV, Kotsis G, Davilis D, Manolopoulos L. Bilateral peritonsillar abscesses:

14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

a case presentation and review of the current literature with regard to the controversies in diagnosis and treatment. Case Rep Med 2011;2011:981924. Dalton RE, Abedi E, Sismanis A. Bilateral peritonsillar abscesses and quinsy tonsillectomy. J Natl Med Assoc 1985;77(10):807-12. Simons JP, Branstetter BF 4th, Mandell DL. Bilateral peritonsillar abscesses: case report and literature review. Am J Otolaryngol 2006;27(6):443-5. Kristensen S, Juul A, Nielsen F. Quinsy: a bilateral presentation. J Laryngol Otol 1985;99(4):401-2. Fasano CJ, Chudnofsky C, Vanderbeek P. Bilateral peritonsillar abscesses: not your usual sore throat. J Emerg Med 2005;29(1):45-7. Kanesada K, Mogi G. Bilateral peritonsillar abscesses. Auris Nasus Larynx 1981;8(1):35-9. Mehanna HM, Al-Bahnasawi L, White A. National audit of the management of peritonsillar abscess. Postgrad Med J 2002;78(923):545-8. Su WY, Hsu WC, Wang CP. Inferior pole peritonsillar abscess successfully treated with non-surgical approach in four cases. Tzu Chi Medical J 2006;18(4):287-90. Licameli GR, Grillone GA. Inferior pole peritonsillar abscess. Otolaryngol Head Neck Surg 1998;118(1):95-9. Kristensen S, Tveterås K. Post-tonsillectomy haemorrhage. A retrospective study of 1150 operations. Clin Otolaryngol Allied Sci 1984;9(6):347-50. Bonding P. Tonsillectomy à chaud. J Laryngol Otol 1973;87(12):1171-82. Fagan JJ, Wormald PJ. Quinsy tonsillectomy or interval tonsillectomy - a prospective randomised trial. S Afr Med J 1994;84(10):689-90. Herbild O, Bonding P. Peritonsillar abscess. Arch Otolaryngol 1981;107(9):540-2. Savolainen S, Jousimies-Somer HR, Mäkitie AA, Ylikoski JS. Peritonsillar abscess. Clinical and microbiologic aspects and treatment regimens. Arch Otolaryngol Head Neck Surg 1993;119(5):521-4.

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Swallowing Exercises Aid Head and Neck Cancer Recovery Patients with head and neck cancers who receive chemoradiation typically have long-term side effects, like difficulty swallowing or need for a feeding tube. But researchers in California have developed a “swallow therapy,” which has been shown to significantly improve post-treatment quality of life. The study, which was recently published in the journal Otolaryngology - Head and Neck Surgery, comes from a team at the University of California, Los Angeles’ Jonsson Comprehensive Cancer Center (JCCC). The researchers say that though surgery and radiation are the “traditional treatments” for the disease, many types are now treated with a combination of chemotherapy and radiation, termed chemoradiation, in order to preserve tissue and structure.

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Gastroenterology

Pseudomembranous Colitis: Do We Need A Screening? Ashish Gautam*, Prabhat Agrawal*, Abhishek Raj*, Ashwini K Nigam*, SUBHASH CHANDRA*, MANISH K BANSAL**

Abstract In the last few decades, increasing use of antibiotics has dramatically increased incidences of antibiotic associated diarrhea. An unopposed homing of Clostridium difficile in ICU and wards put forward new challenges for physicians. Development of diarrhea during or just after hospital stay especially in old patients is a typical clinical presentation of C. difficile diarrhea. Cytotoxin assay from tissue culture is a gold standard diagnostic test but its poor availability, high cost, time bound results and rapidly development of life-threatening complications made us to think of a screening test. Demonstration of pathognomonic summit lesions and pseudomembrane with colonoscopy or sigmoidoscopy is relatively inexpensive, easily available and diagnosis is prompt. Our experience in few patients with colonoscopy makes us to recommend it as a screening test for all clinically suspected patients. Till today, it is refuted as first-line investigation because of good number of false negative results but demonstration of pathognomonic lesions even in few patients saves the life with minimal expenditure and least time wastage before initiation of definitive treatment.

Keywords: Pseudomembranous colitis, summit lesion, antibiotic-associated diarrhea

C

lostridium difficile is a gram-positive, anaerobic, spore-forming bacillus with toxicogenic property. Its presence in intensive care units (ICUs), wards and now even in outpatients has put forward new challenges for treating physicians. Moreover, the cost of treatment and hospital stay increases only because of inadvertent antibiotic use and failure to follow aseptic precautions.1-3 CLINICAL FEATURES Infection from C. difficile has a wide-spectrum of presentation i.e., from asymptomatic carriage to fulminant colitis. Pseudomembranous colitis (PC) is one of the rare but catastrophic presentations of C. difficile infection. Other uncommon presentations are non-PC and a milder form of C. difficile diarrhea. Collectively, these presentations are called C. difficile associated diarrhea (CDAD). Besides associated with C. difficile, PC can occur in less than 25% of

*Assistant Professor **Associate Professor Dept. of Medicine, SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Ashish Gautam Assistant Professor Dept. of Medicine SN Medical College, Agra, Uttar Pradesh E-mail: dr_ashishgautam@yahoo.co.in

other bacterial, viral and toxic causes of diarrhea, gastroenteritis and anorectal fistulas. A patients of PC is typically an old age patients with history of antibiotic use during hospitalization, who develops recurrent diarrhea with or without blood in stools.4 Rarely, patient can present with hypoproteinemia and electrolyte imbalance, hypotension, toxic megacolon, severe sepsis or bowel perforation. Besides age and antibiotic use, other risk factors for PC are use of proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), chronic kidney disease (CKD) and methicillin-resistant Staphylococcus aureus (MRSA) coinfection.5 Rarely, abdominal and pelvic surgeries,6 shigella infection, Crohnâ&#x20AC;&#x2122;s disease, neonatal necrotizing enterocolitis, intestinal obstruction, Hirschsprungâ&#x20AC;&#x2122;s disease and colonic carcinoma are associated with development of PC. DIAGNOSIS The gold standard for diagnosis of C. difficile infection is cytotoxin assay that uses tissue culture.7 It takes 24-72 hours for reporting and also is not easily available even at tertiary healthcare centers. An alternative enzyme immunoassay (EIA) of toxin A and B of C. difficile is less sensitive with 10-20% false negative rate but is relatively easily available and gives result within 24 hours.8 Diagnostic colonoscopy or sigmoidoscopy is less sensitive with high false positive rates for asymptomatic and nonpseudomembranous type of CDAD. Presence of pathognomonic feature summit

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Gastroenterology

Descending colon

Sigmoid colon

Figure 1. Colonoscopy demonstrates multiple yellow white spots in transverse, descending and sigmoid colon.

lesions and pseudomembrane on colonoscopy promptly makes diagnosis of PC and usually do not require tissue culture or EIA. PC is sometimes a fatal condition and requires urgent initiation of treatment.9-13 Johal et al in a study of 136 patients suggest routine sigmoidoscopy in all clinically suspected patients and stool. Cytotoxin is negative for C. difficile.11 Although C. difficile associated diarrhea can present with normal appearing colonic mucosa still a screening colonoscopy of patient with typical clinical presentation can easily clinches diagnosis of PC and early institution of definitive treatment. Also, colonoscopy is available easily at small cities in India, where the facility of tissue culture and EIA for toxin A and B are not available. Colonoscopy is relatively inexpensive, allows assessment of disease severity and facilitates subsequent management. Ulcerative colitis, Crohnâ&#x20AC;&#x2122;s disease, infectious colitis and other similar conditions can be easily differentiated after colonoscopy. We present here two cases in which an early colonoscopy helped us to make out an early diagnosis, institute specific therapy that saved the lives of patients. CASE 1 A 64-year-old female patient was shifted from orthopedic recovery ward to medicine ward for complaint of severe diarrhea since five days. She had been operated for hip fracture 20 days back and was in recovery phase. Most of her antibiotics had been stopped three days back when she developed first diarrheal episode. A presumptive diagnosis of antibiotic associated diarrhea was made and she was

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

put on probiotics. Her general condition continued to worsen so her stool was sent for culture and intravenous ciprofloxacin and metronidazole was started. Ultrasonography of abdomen was normal. Her colonoscopy was planned till report of culture awaited. Her colonoscopy demonstrated multiple yellow white spots in transverse, descending and sigmoid colon with continuous membrane in rectum and anal canal. Her general condition rapidly started improving and she become asymptomatic after 10 days of intravenous and four days of oral metronidazole therapy. Retrospective evaluation of antibiotic use disclosed that she was given cephalosporins and aminoglycosides after surgery. Stool culture report later confirmed presence of Clostridium species. CASE 2 A 72-year-old female was admitted for bleeding per rectum, loose stools since past three weeks, pedal edema and altered senses since past one week. She was operated and given intravenous clindamycin for gangrene of right middle finger two weeks prior to development of loose stools. Her vitals were stable and except for presence of pallor and anasarca, general examination was normal. She was drowsy but no neurological deficit was observed. Abdomen was soft and nontender and there was no apparent organomegaly. Her hemoglobin was 3.5 gm%; serum albumin was 2.13 gm%, serum creatinine 0.75 mg%, and alanine aminotransferase/aspartate aminotransferase (ALT/ AST) were 34/24 U/l. Escherichia coli Ă&#x2014; 106 was grown


Gastroenterology Table 1. Differences between Antibiotic-associated Diarrhea from C. difficile Infection and from Other Causes Characteristic

AAD from C. difficile infection

AAD from other causes

Most commonly implicated antibiotics

Clindamycin, cephalosporins, penicillins, fluoroquinolones

Clindamycin, cephalosporins, ampicillin or co-amoxyclav

History

Usually no history of antibiotic intolerance

History of diarrhea with antibiotic therapy is common

Diarrhea

May be florid; evidence of colitis with cramps, fever and fecal leukocytes is common

Usually moderate in severity (nuisance diarrhea) without evidence of colitis

Findings on CT or colonoscopy

Evidence of colitis is common; pseudomembranes often are present

Usually normal

Complications

Hypoalbuminemia, anasarca, toxic megacolon; relapse can occur after treatment with metronidazole or vancomycin

Usually none except occasional cases of volume depletion

Results of assay for C. difficile toxin

Positive

Negative

Epidemiologic pattern

May be epidemic or endemic in hospitals or long-term care facilities

Sporadic

Withdrawal of implicated antibiotic

Condition can resolve but often persists or progresses

Condition usually resolves

Antiperistaltic agents

Contraindicated

Often useful

Oral metronidazole or vancomycin

Prompt response

Not indicated

Clinical features

Treatment

on stool culture with sensitivity for all third- and fourthgeneration cephalosporins. She was given ceftriaxone 1 g b.i.d. and metronidazole 100 ml t.d.s. Total 6 units of blood transfusions done and 100 ml of intravenous albumin was given for six days. Her general condition improved but except for diarrhea all symptoms subsided. Ultrasonography of abdomen showed an ill-defined mass of 2.6 Ă&#x2014; 3.2 cm in right iliac fossa with bilateral minimal pleural effusion. Her sigmoidoscopy demonstrated yellow white membranous layer on colonic mucosa with intermittent bleeding ulcer. In descending colon, the membrane scattered into spots and normal appearing intermittent mucosa. These lesions were summit lesions, which were pathognomonic of PC. She was started with vancomycin after which she improved dramatically in 48 hours and complete recovery occured in next 14 days. Many more cases present to us but most of them respond very well on oral metronidazole therapy.12 So, on above experience we propose to use sigmoidoscopy as screening test for patients who are suspected to have antibiotic associated diarrhea on clinical grounds. A keen observer can easily make diagnosis of PC on colonoscopy if typical lesions are

present. The prime concern is to differentiate between antibiotic associated diarrhea (AAD) from C. difficile and AAD due to other causes. Table 1 differentiate between the clinical features and treatment of above two. DISCUSSION Pseudomembranous colitis is a rare but frequently fatal presentation of C. difficile-associated diarrhea. Although gold standard for diagnosis of C. difficile infection is cytotoxin assay that uses tissue culture, still colonoscopy in an unprepared bowel, which is considered inappropriate for diagnosis, can be sometimes rewarding. Demonstration of pathognomonic summit lesions on colonoscopy makes prompt diagnosis and rapid institution of specific treatment and is thus lifesaving. We hereby recommend a diagnostic colonoscopy as screening test in all clinically suspected patients of antibioticassociated diarrhea. It is easily available, makes prompt diagnosis and helps to differentiate from other similar conditions, is relatively less expensive, needs only a keen observer at cost of high false negative rate.

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Gastroenterology REFERENCES 1. McFarland LV. Epidemiology of infectious and iatrogenic nosocomial diarrhea in a cohort of general medicine patients. Am J Infect Control 1995;23(5):295-305. 2. Lai KK, Melvin ZS, Menard MJ, Kotilainen HR, Baker S. Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control. Infect Control Hosp Epidemiol 1997;18(9):628-32. 3. Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18(2):181-7. 4. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320(4):204-10. 5. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of communityacquired Clostridium difficile-associated disease. JAMA 2005;294(23):2989-95. 6. Wakefield RD, Sommers SC. Fatal membranous staphylococcal enteritis in surgical patients. Ann Surg 1953;138(2):249-52.

7. Merz CS, Kramer C, Forman M, Gluck L, Mills K, Senft K, et al. Comparison of four commercially available rapid enzyme immunoassays with cytotoxin assay for detection of Clostridium difficile toxin(s) from stool specimens. J Clin Microbiol 1994;32(5):1142-7. 8. Kelly CP, LaMont JT. Clostridium difficile - more difficult than ever. N Engl J Med 2008;359(18):1932-40. 9. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994;330(4):257-62. 10. Kwon JH, Kelly CP. Clostridium difficile and antibioticassociated diarrhea. In: Advanced Therapy in Gastroenterology and Liver Disease. 5th edition, Bayless RM, Diehl AM (Eds.), BC Decker: Hamilton, Ontario 2005:p.302. 11. Johal SS, Hammond J, Solomon K, James PD, Mahida YR. Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004;53(5):673-7. 12. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care 2007;13(4):450-5. 13. Mylonakis E, Ryan ET, Calderwood SB. Clostridium difficile - Associated diarrhea: A review. Arch Intern Med 2001;161(4):525-33.

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Vitamin D Intake-associated with Reduced Risk for Crohn’s Disease Increased intake of vitamin D may significantly reduce the risk for Crohn’s disease (CD) in women, according to an article published online December 12 and in the March issue of the journal Gastroenterology. ÂÂ This study involved 72,719 women who returned the 1986 questionnaire. They had data on both vitamin D intake and physical activity and did not have a history of CD or ulcerative colitis (UC). ÂÂ Diagnosis of CD was based on a typical history of four weeks or longer and was confirmed by radiologic, endoscopic or surgical evaluation. ÂÂ The diagnosis of UC was based on typical clinical presentation of four weeks or more and endoscopic, radiologic or surgical evaluation. ÂÂ Mean age of the participants at baseline was 53 years, mean body mass index (BMI) was 25.4 kg/m2, mean physical activity was 13.2 metabolic hours per week, 94.5% were white and 36.6% never smoked. ÂÂ A documented 122 cases of CD and 123 cases of UC were recorded during 1,492,811 person-years of follow-up. The median predicted 25(OH)D level was 27.6 ng/ml. ÂÂ Women in the lowest quartile of predicted 25(OH)D level compared with those in the highest quartile had a higher BMI, were less active, tended to reside in the Northern or Midwestern regions of the United States, and had lower intake levels of dietary or supplemental vitamin D. The median age of diagnosis of CD was 64.0 years; for UC, it was 63.5 years. ÂÂ The median interval between assessment of plasma 25(OH) D levels and disease diagnosis was 12 years for UC and 10 years for CD. ÂÂ For every 1 ng/ml increase in predicted 25(OH)D level, the risk for CD was reduced by 6%. ÂÂ For UC, there was also a reduction in risk, but it was nonsignificant at 4%. ÂÂ Women in the highest two quartiles of 25(OH)D levels had multivariate hazard ratios (HRs) of 0.50 and 0.55, respectively, for CD. ÂÂ Each 100 IU/day increase in total intake resulted in a 10% reduction in UC risk and a 7% reduction in CD risk. ÂÂ For vitamin D intake from diet and supplements based on quartile distribution, there was a significant linear inverse trend for vitamin D intake and UC risk, but this trend was weaker for CD. ÂÂ Intakes of 800 IU/day or higher resulted in greater reductions in the risks for UC and CD ÂÂ Vitamin D intake was inversely associated with the risks for CD and UC, vitamin D insufficiency or deficiency was an important mediator in the pathogenesis of UC and CD, and assessment of vitamin D status should be a part of the assessment of inflammatory bowel diseases.

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Infectious Diseases

Serostatus Disclosure and Safer Sex in HIV-positive Man: Case Study Sangita Patel*, Shilpa N Patel**, Rajendra K Baxi*, Carol E Golin**,†,‡,#, Kedar Mehta*, Mansi Mehta*, Harsh Bakshi*, Kalpita Shingrapure*, Ekta Modi*, Priyanka Coonor*

Abstract Disclosure of one’s human immunodeficiency virus (HIV)-positive serostatus to a spouse or sex partner is important, particularly to inform the partner of the need to take precautions to prevent HIV transmission. Thus, understanding the process of disclosure is important to facilitating it to occur more often. Such understanding can best be achieved through a qualitative study (in-depth-interview) that elicits and systematically explores individuals’ stories of what has happened to them after disclosure of HIV.

Keywords: Serostatus disclosure, HIV-positive, safe sex, India Case Study

Results

Research indicates that upto one-third of individuals diagnosed with human immunodeficiency virus (HIV)infection continue to have unprotected sex, at times without informing their sexual partners, who may be of negative or unknown serostatus.1,2 Disclosure of one’s HIV-positive serostatus to a spouse or sex partner is important, particularly to inform the partner of the need to take precautions to prevent HIV transmission. Thus, understanding the process of disclosure is important for facilitating it to occur more often. Such understanding can best be achieved through a qualitative study (in-depth-interview) that elicits and systematically explores individuals’ stories of what has happened to them after disclosure of HIV. The study received ethical clearance from local institutional review board and National Institute Health (NIH). Here we are presenting only one case study from our Indo-US project on Formative study on HIV prevention needs of HIV-infected persons in Gujarat, India.

A married male, aged 44 years, has been diagnosed HIV positive since 1997. He was tested for HIV during medical examination as a requirement for a new job out of India. The doctor in Mumbai who examined him did not explain to him personally about his seropositive status but rather the patient found out from the counseling and testing counselor back in Vadodara. The patient did not receive any pre- or post-test counseling.

*Dept. of Community Medicine, Medical College Baroda, Gujarat **UNC Cecil G Sheps Center for Health Services Research †Dept. of Medicine, UNC School of Medicine; ‡Dept. of Health Behavior and Health Education, UNC School of Public Health, University of North Carolina at Chapel Hill #UNC Center for AIDS Research, Medical College, Baroda Address for correspondence Dr Sangita Patel Associate Professor, Dept. of Preventive and Social Medicine Medical College, Baroda, Gujarat

During an in-depth-interview with our research team, he admitted to being involved in high-risk behavior, which included visiting commercial sex workers (CSWs)and drinking alcohol, as the route by which he believed he had acquired HIV, “Outside sexual relations with about 2-3 females. Before marriage, I was working in Bombay as a crane operator. At that time, I had to move about frequently, covered entire of India - upto Gulbarga. I used to drink a lot at that time.” He did not disclose his HIV-positive status to his wife, who is his second wife since his first wife passed away. The married male continued to use condoms consistently during sexual relations with his second wife, but has not yet disclosed his HIV status to her. He confessed, “I don’t even take the name of sex now. I don’t have any interest left in it now. We have relations once in a month.” He had to disclose his HIV-positive status to his mother due to his poor health. The participants’ wife wants to have children but he has not agreed to this. This disagreement between him and his wife has led to intimate partner violence, “My wife fights a lot

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Infectious Diseases with me. She wants children. I cannot have children now, since I have this disease. I sometimes have to beat her, she is very hot tempered.” Two months later, he called the investigator and said that his wife came to know about his HIV status accidentally by occupational health doctor in industry. So, his wife moved back to her parent’s house. Again after six months, she came back to her husband and both decided to stay together which showed her care and acceptance of him. Both finally practiced correct and consistent condom use and there has not been any insistence for a child by the wife. Discussion Practicing safer sex is a complex behavior with multiple determinants that vary by individual and social context. Patient accepted having acquired HIV infection through his premarital sexual relations (visiting CSWs). Counseling was not given by doctor in Mumbai but it was given by the Integrated Counseling Testing Centre (ICTC) counselor at ICTC, Vadodara, which was the reason for his behavior change as suggested by the patient. After HIV diagnosis, the patient reported practicing consistent condom use, without disclosing his status to his wife. A qualitative study done in South India by Sri Krishnan found that participants’ sexual behaviors became less risky after their HIV diagnosis and consistent condom use.3 The reason which facilitated consistent condom use was mainly the desire to prevent further HIV spread to partners. Condom use as a safe sex practice among serodiscordant couples is very essential. Here one of the major barriers to condom use was the desire of one partner (wife) to have children. Because the husband had not disclosed his seropositive HIV status to his wife, she did not see the need to use condoms. Similar findings were observed by Chakrapani et al, in India.4 In this study, nondisclosure to the wife on part of the husband led to intimate partner violence, as the husband insisted on condom use while the wife desired to have children. It was only after inadvertent disclosure by occupational health doctor, the wife became aware of her husband’s HIV status. This suggests that counselors and healthcare staff need to work very closely with their clients to encourage them to bring their spouse to support and facilitate disclosure of their HIV status. In this study, several factors including perceived HIVassociated stigma, fear of discrimination and fear of family breakdown were found to influence husband’s decision not to disclose his HIV-positive status. In India, law supports disclosure of an otherwise confidential

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report to the spouse by the service provider in order to prevent harm to the spouse.5 Contradictory to this, some studies outside of India mention that increasing disclosure of serostatus to sex partners may not reduce the prevalence of unsafe sex.6,7 However, a study done by Loubiere in Cameroon demonstrated that HIV disclosure to one’s main partner was related to safe sexual practices.8 Conclusions The benefits of HIV disclosure to family that emerge are support and care from family members, protecting the sero-negative spouse from HIV and avoiding unintended pregnancy. Hence, HIV counseling must better help people living with HIV/AIDS (PLWHA) to plan their future with HIV, including how they will avoid being stigmatized while disclosing their HIV-positive status, avoiding transmitting HIV and addressing childbearing. References 1. Wolitski RJ, Rietmeijer CAM, Goldbaum GM, Wilson RM. HIV serostatus disclosure among gay and bisexual men in four American cities: General patterns and relation to sexual practices. AIDS Care: Psychological and Sociomedical Aspects of AIDS/HIV. 1998;10(5):599-610. 2. Kalichman SC. HIV transmission risk behaviors of men and women living with HIV-AIDS: prevalence, predictors, and emerging clinical interventions. Clin Psychol Sci and Pract 2000;7(1):32-47. 3. SriKrishnan AK, Hendriksen E, Vallabhaneni S, et al. Sexual behaviors of individuals with HIV living in South India: a qualitative study. AIDS Education and Prevention. 2007;19(4):334-45. 4. Chakrapani V, Newman PA, Shunmugam M, Dubrow R. Prevalence and contexts of inconsistent condom use among heterosexual men and women living with HIV in India: implications for prevention. AIDS Patient Care and STDs 2010;24(1):49-58. 5. Col Zile Singh, Lt.Col.A.Banerjee. HIV/AIDS : Social and ethical issues. MJAFI 2004;60:107-8. 6. Sullivan KM. Male self-disclosure of HIV-positive serostatus to sex partners: a review of the literature. J Associat Nurs AIDS Care: JANAC 2005;16(6):33-47. 7. Simoni JM, Pantalone DW. Secrets and safety in the age of AIDS: does HIV disclosure lead to safer sex? Top HIV Med 2004;12(4)109-18. 8. Loubiere S, Peretti-Watel P, Boyer S, Blanche J, Abega S-C, Spire B. HIV disclosure and unsafe sex among HIVinfected women in Cameroon: results from the ANRSEVAL study. Social Sci Med 2009;69(6):885-91.


Infectious Diseases

HIV and Infant Feeding VK Agrawal

Abstract Breastfeeding is an unequalled way of providing ideal food for healthy growth and development of infants. Breast milk promotes sensory and cognitive development, and protects the infant against infections and chronic diseases. With the onset of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic and the recognition that HIV-infected mother can transmit HIV to their infants through breastfeeding, specific recommendations apply to infants born to HIV-infected mothers. Estimated risk of mother-to-child transmission of HIV in the absence of intervention during breastfeeding vanes from 5% to 20%. It is a public health responsibility to prevent HIV infection in infants and young children-especially in countries with high rates of HIV infection among pregnant women, and to support optional breastfeeding to prevent mortality and illness due to diarrhea and respiratory infections. Given the need to reduce the risk of HIV transmission to infants while minimizing the risk of other causes of morbidity and mortality, United Nation Agencies guidance states that when replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected mothers is recommended. Otherwise, exclusive breastfeeding is recommended during first month of life.

Keywords: Human immunodeficiency virus, mother-to-child transmission, infant feeding

T

he global strategy for infant and young child feeding adopted in 2002 clearly sets out that infants should be exclusively breastfed for the first six months of life to achieve optimal growth, development and health. Afterwards, infants should receive nutritionally adequate and safe complementary food, while breastfeeding continues upto two years of age and beyond.1 However, the feeding of children living in the exceptionally difficult circumstances of being born to an human immunodeficiency virus (HIV)-positive women merits special consideration due to risk of HIV transmission through breast milk as well as due to reported higher mortality rate in HIV-infected mothers who breastfed their infants compared with those who fed their infants with formula feeding.2 Breastfeeding is associated with a significant additional risk of HIV transmission from mother-to-child as compared to nonbreastfeeding. This risk depends on clinical factors and may vary according to pattern and duration of breastfeeding. In untreated women who continue breastfeeding after the first year, the absolute risk of transmission through breastfeeding is

Associate Professor Dept. of Preventive and Social Medicine, Armed Forces Medical College Pune, Maharashtra

10-20%.3 Replacement feeding earns an increased risk of morbidity and mortality associated with malnutrition and associated with infectious diseases other than HIV. This is especially high in first six months of life and decreases thereafter. A number of observational studies have documented increased mortality among nonbreastfed infants. More recently, an analysis of pooled data from three countries has provided age specific odds ratios for the protective effect of breastfeeding.4 Health services worldwide are developing and implementing programs to reduce mother-to-child transmission (MTCT) of HIV, including antiretroviral therapy and artificial feeding. These initiatives increase the urgency of efforts to understand the overall mortality risks associated with different infant feeding strategies under different conditions. Evidence for HIV Transmission Through Breast milk3 ÂÂ

The virus has been found in breast milk, and women with detectable virus are more likely to transmit infection compared to women who do not have detectable virus.

ÂÂ

HIV infection has occurred in breastfed infants of mother who were not infected with HIV during pregnancy or at delivery but who became infected while breastfeeding.

ÂÂ

Infants born to HIV uninfected mothers have been infected by breast milk from HIV-infected wet nurses or by breast milk from unscreened donors.

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Infectious Diseases ÂÂ

Infants born without infection to HIV-infected women, and who were diagnosed as HIV uninfected at six months of age, have been found to be infected after this age, with breastfeeding as the only concurrent risk factor.

Risk of MTCT of HIV By far the principal source of HIV infection in young children is MTCT. The virus may be transmitted during pregnancy, labor or delivery or through breastfeeding. About two-thirds of infants born to HIV-infected mother will not be infected, even with no interventions, such as antiretroviral prophylaxis or caesarean section.5 About 15-25% of infants of HIVinfected women will be infected during pregnancy or during labor or delivery, an additional 5-20% may become infected during breastfeeding (Table 1). The risk of MTCT of HIV through breastfeeding appears to be greatest during the first month of infant life but persists as long as breastfeeding continues.3 Reported rates of transmission through breastfeeding by a mother-infected before delivery range from 0.2% to 0.9% per month.6 However, because of the inability to distinguish before and during delivery, these rates are based on estimates for transmission after the first six weeks to two months. Decock et al estimated that rate of transmission during the early neonatal period may be several times higher, amounting to a transmission rate over the first two months of an additional 5-10%.5 Monthly rate of transmission in the early neonatal period from various studies were 4.5%,7 1.9%,8 2.9%9 and 1.8%,10 with arithmatic mean of 2.8%. Risk Factors for HIV Transmission through Breastfeeding A number of factors increase the risk of HIV transmission through breastfeeding3 ÂÂ

Recent infection with HIV: A woman who has been infected with HIV during delivery or while breastfeeding is more likely to transmit the virus to infant.

ÂÂ

HIV disease progression: As measured by low CD4+ count or high RNA viral load in plasma, with or without severe clinical symptoms.

ÂÂ

Breast condition: Subclinical or clinical mastitis, cracked or bleeding nipples or breast abscess.

ÂÂ

Oral thrush: In the infant.

ÂÂ

Longer duration of breastfeeding: An infant continues to be at risk of infection as long as they are exposed to HIV-contaminated milk.

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

Table 1. Estimated Risk and Timing of MTCT of HIV in the Absence of Interventions Timing

Transmission rate

During pregnancy

5-10%

During labor and delivery

10-15%

During breastfeeding

5-20%

Overall without breastfeeding

15-25%

Overall with breastfeeding to 6 months

20-35%

Overall with breastfeeding to 18-24 months

30-45%

Mode of breastfeeding may also affect the risk of HIV transmission. Exclusive breastfeeding may be less likely to transmit HIV than mixed feeding.

Simulation Models to Assess the Risk of HIV Transmission Through Breastfeeding A number of studies have been published that use simulation models to assess the risk of HIV transmission through breastfeeding.11-13 These simulation models unanimously conclude that under conditions of high infant mortality and high-risk of death from replacement feeding, breastfeeding is safer infant feeding strategy, despite the risk of HIV transmission. Although many of factors affecting the risks of HIV transmission through breastfeeding and infant mortality vary dramatically with age, most of these analyses treat the whole of infancy as a single homogenous period. Ross et al,14 using recent estimates of the age specific risk of both HIV transmission through breastfeeding and death from artificial feeding, developed a spreadsheet simulation model to predict HIV-free survival during seven age intervals from 0 to 24 months for five different infant feeding scenarios in resource poor settings. The study shows that under conditions common in countries with high HIV prevalence, breastfeeding by the HIV-infected mother has an advantage in terms of HIV-free survival for infants during the first six months after birth, despite the risk of MTCT.

Infant Feeding Options Designed to Prevent MTCT HIV-infected pregnant women should consider their infant feeding options. They should seek to balance the nutritional and other benefits of breastfeeding with risks of transmitting HIV to their infants and choose between exclusive breastfeeding and replacement


Infectious Diseases feeding (commercial infant formula or home modified animal milk) or other breast milk options (heat-treated expressed milk, wet nursing or donors milk from a milk bank). When replacement feeding is acceptable, feasible, affordable, sustainable and safe, HIV-infected mother should avoid breastfeeding completely. When these conditions are not present, HIV-infected women who choose to breastfed are recommended to do so exclusively for the first few months, and then, over a period of a few days to few weeks rather than abruptly, to stop breastfeeding (exclusive breastfeeding with early cessation), provided the conditions for replacement feeding or other breast milk options are in place.15 Mixed feeding with both breast milk and other feeds has been associated with higher risk of HIV infection for the infant than exclusive breastfeeding.16 In an observational study in South Africa, exclusive breastfeeding during the first three month of life was associated with a lower transmission risk than mixed feeding, and number of studies are underway to investigate further the association between infant feeding modality, risk of transmission through breastfeeding and infant health.15 The other breast milk options to reduce HIV infectivity are wet nursing by a tested, HIV-negative women, treating breast milk to render it noninfectious and using milk from breast milk banks. All means of modifying or treating breast milk to render it noninfectious involve expressing milk, and women have to taught and supported to sustain this process for long periods, to avoid such problems as mastitis. This should not prevent the option being offered; infant feeding counseling should be provided when women choose this option, and issues of hygiene and stigma should be addressed. Expression and heat treatment could be a temporary solution during periods of increased risk transmission as in cases of cracked nipples or breast abscess, and for low-birth-weight or sick infants for whom the risk of replacement feeding is greater, and during transition from exclusive breastfeeding to replacement feeding.17 Current or prospective research into MTCT The main current public health research question is whether breastfeeding by HIV-infected mothers can be made safer on to transmission risk, given the possible adverse effects of refraining from breastfeeding. Various ongoing or planned trials and studies concern either mode of infant feeding (exclusive or mixed) or anteretroviral therapy to either mother or infant over

the breastfeeding period. World Health Organization (WHO) is supporting research in South Africa on the risk of postnatal transmission of HIV in exclusively breastfed infants, and research in Zambia on the risk of HIV transmission through breast milk associated with sub-clinical mastitis and other infections. WHO is also supporting operational research on HIV and infant feeding counseling in Brazil and South Africa.18 References 1. Exclusive breast-feeding. Available at http://www.who. int/child-adolescont-health/nutrition/infant-exclusive. htm. Accessed on 08 February 2006. 2. Neluah R, Richardson BA, John G. Effects of breastfeeding on mortality among HIV-infected women: a randomised trial. Lancet 2001;357:1651-5. 3. WHO (2001b). New data on the prevention of mother to child transmission of HIV and their policy implicationconclusions and recommendations. WHO Technical Consultation on behalf of the UNFPA/UNICEF/WHO/ UNAIDS Iinter-agency task team on mother to child transmission. Geneva: WHO 2001. Report in WHO/ RHR/01.28. 4. WHO Collaborative Team on the role of breast feeding in the prevention of infant mortality. Effect of breastfeeding on infant and child mortality due to noninfectious diseases in less developed countries: a pooled analysis. Lancet 2000;355:451-55. 5. Decock KM, Fowler MG, Mercier E. Prevention of mother to child HIV transmission in resource poor countries: translating research into policy and practice. JAMA 2000;283:1175-82. 6. Fawzi W, Msamanga G, Spiegelman D. Transmission of HIV-1 through breastfeeding among women in Dares Salaam, Tanzania. Journal of Acquir Immune Defic Syndr 2002;31:331-8. 7. Nduati R, John G, Mbori-Ngacha D. Effects of breastfeeding and formula feeding on transmission of HIV-1: a randomized trial. JAMA 2000;283:1167-74. 8. Coutsoudis A, Pillay K, Kuhn L, Spooner E, Tsai WY, Coovadia HM. Method of feeding and transmission of HIV-1 from mother to children by 15 months of age: prospective cohort study from Durban, South Africa. AIDS 2001;15:379-87. 9. Moodley D, Moodley J, Cooradia H. A multicentre randomized controlled trial of nevirapine versus a combination of zidovidine and lamivudine to reduce intrapartum and early postpastum mother to child transmission of HIV-1. J Infect Dis 2003;187:725-35. 10. Petra Study Team. Elficacy of three short-course regiments of zidarudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a

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Infectious Diseases randomised, double blind, placebo controlled trial. Lancet 2002;359:1178-86.

to-child transmission of HIV. Am J Public Health 2004;94(7):1174-80.

11. Kuhan L, Stein Z. Infant survival, HIV infection, and feeding alternatives in less - developed countries. Am J Public Health 1997;87:926-31.

15. WHO. HIV transmission through breastfeeding. A review of available evidence. available at www.who.int/childadolescent-health/publication/nutrition/ISBN 9241562714 accessed in Feb 2006.

12. Walley J, Witter S, Nicoll A. Simplified antiviral prophylaxis with or and without artificial feeding to reduce mother to child transmission of HIV in low and middle income countries: modelling positive and negative impact on child survival. Med Sci Mont 2001;7:1043-51. 13. Bertolli J, Hu DJ, Neiburg P, Macalalad A, Simonds RJ. Decision analysis to guide choice of intervention to reduce mother to child transmission of HIV. AIDS 2003;17:2089-98. 14. Ross JS, Labbok MH. Modeling the effects of different infant feeding strategies on infant survival and mother-

16. WHO (2001a). The optimal duration of exclusive breastfeeding. Report of an expert consultation. Geneva, 28-30 March 2001. WHO/NHD/01.09 and WHO/FCH/ CAH/01.24. 17. Rollins N. Preventing postnatal transmission of HIV-1 through breastfeeding modifying infant feeding practices J Acquired Immune Defic Synd 2004;35(2):132-9. 18. WHO (CAH). HIV and infant feeding. available at http:// www.who.inf/child/alolescenthealth/NUTRITION/HIVInfant.htm. Accessed in February 2006.

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Research Identifies How Mouth Cells Resist Candida Infection Candida albicans is a common fungus found living in, and on, many parts of the human body. Usually this species causes no harm to humans unless it can breach the body’s immune defences, when it lead to serious illness or death. It is known as an opportunistic pathogen that can colonise and infect individuals with a compromised immune system. New research, presented at the Society for General Microbiology’s Autumn Conference, gives us a greater understanding of how mucosal surfaces in the body respond to C. albicans to prevent damage being done during infection. Researchers from King’s College London focused on oral epithelial cells, a mucosal layer of cells that line the mouth, providing a barrier against microbes. The group challenged oral epithelial cells grown in vitro with C. albicans, looking at gene expression six and 24 hours after infection.

Comparison of four Different Immunization Schedules for Pneumococcal Vaccine finds no Significant Difference in Antibody Levels The use of four different 13-valent pneumococcal conjugate vaccine immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels between the infants after the booster dose at 12 months of age for almost all serotypes, according to a study in the September 4 issue of JAMA. “The World Health Organization (WHO) estimated that more than 8,00,000 children younger than five years died from pneumococcal disease in 2000, making it the leading vaccine-preventable cause of death. Since, the licensure in 2000 of the first 7-valent pneumococcal polysaccharide conjugate vaccine (PCV) for infants, many countries have added PCV to their existing national immunization programs. As a result, PCV immunization schedules differ between countries with respect to number of doses, age at vaccinations, and intervals between doses,” according to background information in the article. “The optimal vaccine schedule for infants should provide maximal, sustained direct and indirect protection against invasive pneumococcal disease while using a minimal number of doses. The latter is particularly relevant in the context of overcrowded national immunization programs, public resistance to vaccines and cost-effectiveness estimates.”

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Infectious Diseases

How to Manage Hepatitis B Infection? Deepak Amarapurkar*, Nikhil Patel*

Abstract Hepatitis B is a potentially life-threatening infection caused by the hepatitis B virus (HBV), which attacks the liver and causes both acute and chronic disease. Presence of virus in infected host relies on demonstration of hepatitis B surface antigen/ hepatitis B virus-DNA (HBsAg/HBV-DNA) in serum/liver tissue. No treatment is required for acute hepatitis B. Patients with immunosuppressed state like chronic liver failure, transplant recipient and patients on cancer chemotherapy with acute hepatitis B may be treated with antivirals under study protocol or at expert centers. Screening of family members for HBsAg and antiHBs is recommended. If both the markers are negative they should be vaccinated and vaccine success should be confirmed with anti-HBs testing

Keywords: Hepatitis B, aminotransferase, HBsAg, fulminant hepatitis B, chronic necoinflammatory disease DEFINITIONS AND DIAGNOSTIC CRITERIA Following definitions and diagnostic criteria for various disease states in hepatitis B infection are considered most appropriate for day-to-day practice.

HBV Infection It is presence of virus in infected host, which relies on demonstration of hepatitis B surface antigen/hepatitis B virus-DNA (HBsAg/HBV-DNA) in serum/liver tissue.

Acute Hepatitis B Diagnosis is based on history, raised aminotransferase and presence of HBsAg and immunoglobulin (IgM) anti-HBc. (In previous unknown status- possibility of reactivation of chronic HBV infection should be considered and HBsAg clearance at six months will suggest acute hepatitis.)

Fulminant Hepatitis B Severe form of acute hepatitis B complicated by liver failure within 24 weeks.

Chronic Hepatitis B with Active Liver Disease It is a chronic necroinflammatory disease of liver caused by HBV. Diagnostic criteria are as follows: HBsAg positive >6 months, HBV-DNA >105 copies/ ml, persistent or intermittent elevated alanine amino-

*Dept. of Gastroenterology Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra

transferase/aspartate aminotransferase (ALT/AST) levels and liver biopsy (not mandatory) showing chronic hepatitis- necroinflammatory score ≥4. It is subdivided into two categories on serology basis: ÂÂ

Hepatitis B ‘e’ antigen (HBeAg) positive chronic hepatitis B (HBeAg and HBV-DNA present in serum with anti-HBe negative)

ÂÂ

HBeAg negative chronic hepatitis B (anti-HBe present and HBeAg absent in serum, HBV-DNA fluctuate).

Chronic hepatitis B infection with no evidence of active liver disease: (inactive HBsAg carrier state). It is defined as a persistent HBV infection of liver without significant ongoing necroinflammatory disease. Diagnosis is based on demonstration of HBsAg positive >6 months, no sign/symptoms of liver disease, normal AST and ALT, HBeAg negative, anti-HBe positive, HBVDNA <105 copies/ml, (optional) persistently normal ALT/AST levels and liver biopsy (optional) confirming absence of significant hepatitis (necroinflammatory score <4). Differentiation from chronic HBeAg negative hepatitis B requires serial testing of ALT and HBV-DNA for one year before designating carrier state. ACUTE HEPATITIS B Diagnosis is based on history, raised aminotransferase and presence of HBsAg and IgM anti-HBc. No treatment is required for acute hepatitis B. Patients with immunosuppressed state like chronic liver failure, transplant recipient and patients on cancer

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357


Infectious Diseases chemotherapy with acute hepatitis B may be treated with antivirals under study protocol or at expert centres. Patient with acute presentation of chronic HBV infection should be treated with antiviral agents. Lamivudine is preferred drug in this situation and treatment needs to be continued for 6-12 months after resolution of hepatitis. Screening of family members for HBsAg and anti-HBs is recommended. If both the markers are negative they should be vaccinated and vaccine success should be confirmed with anti-HBs testing, one month after the last dose. In case of fulminant hepatitis B, patients should be hospitalized and treated on routine management for fulminant hepatic failure and possibility of liver transplantation should be considered.1

ÂÂ

Family screening with HBsAg and anti-HBs, if negative, vaccinate them and success of vaccination should be confirmed with anti-HBs testing.

ÂÂ

Protected intercourse until partner has developed protective antibodies. Eventual offspring needs active and passive vaccination. If unrecognized, the baby is at risk of fulminant hepatitis.

ÂÂ

Alcohol should be avoided.

ÂÂ

The patients should be made aware of the possibility of reactivation or superinfection by other viruses and advised to consult their physician if there is jaundice, malaise or increased fatigue.

ÂÂ

They should regularly follow-up at every 6-12 monthly intervals with ALT.

ÂÂ

If more than 50 years of age or family history of HCC- AFP and USG every 6-12 monthly should be done.

ÂÂ

They should not be denied employment or hospital treatment. Universal precautions should be taken while treating such patients in the hospital.

ASYMPTOMATIC HBsAg CARRIER ÂÂ

No treatment is required.

ÂÂ

Reassurance should be given to the patients.

Table 1. Recommendations for Antiviral Treatment for Chronic Hepatitis B Infection Disease status

Indications

Drugs used

Chronic hepatitis B

HBV DNA >20,000 IU/ml and ALT >2 times of ULN

Interferon/Peginterferon/Lamivudine/Adefovir/ Telbuvidine/Entecavir

HBV DNA >2,000 IU/ml

Interferon/Peginterferon/Lamivudine/Adefovir/ Telbuvidine/Entecavir

HBeAg positive Chronic hepatitis B HBeAg negative Compensated cirrhosis

and ALT >2 times of ULN HBV DNA detectable and any level of ALT

Decompensated cirrhosis

HBV DNA detectable and any level of ALT

Lamivudine/Adefovir/Telbuvidine/Entecavir Interferon/Peginterferon (should be used with caution) Lamivudine/Adefovir Interferon and Peginterferon contraindicated no data on Telbuvidine and Entacavir

Table 2. Various Drugs Available for Treatment of Chronic Hepatitis B Drug

Dosage

Duration

Response rate

Development of resistance

Safety

Interferon

6 mIU daily s.c.

24 wks

30-40%

No

Poor

Peginterferon/ Interferon

1.5 mg/kg body weight weekly s.c.

48 wks

40 -45%

No

Poor

Thymosin-a

1.6 mg twice a week s.c.

48 wks

30-40%

No

Good

Lamivudine

100 mg p.o.

>48 wks

18%

20-80% from 1 to 4 years

Excellent

Adefovir

10 mg p.o.

>48 wks

12%

0-20% from 1 to 4 years

Excellent

Entacavir

0.5 or 1 mg p.o.

>48 wks

30%

No resistance in naïve patients for two years, 5-12% in two years in LAM treated patients

Excellent

Telbuvidine

300 mg p.o.

>48 wks

20%

4-12% in two years

Excellent

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013


Infectious Diseases ÂÂ

For healthcare worker, they should be allowed to do routine designated duties and there is no need for changing the duty. They must follow universal precautions carefully.

ÂÂ

They should not be allowed to donate blood or organ or semen.

ÂÂ

For pregnant women-vaccinate the newborn at birth with active and passive immunization within 12 hours of the birth.

ÂÂ

Close monitoring is required if undergoing chemotherapy or immunosuppressive medications

Suggested reading 1. Liaw YF, Leung N, Guan R, et al. For Asia Pacific consensus update working party on chronic hepatitis B. Asian Pacific

consensus statement on management of chronic hepatitis B: 2005 update. Liver International 2005;25:472-89. 2. Keeffe EB, Dieterich DT, Han SB, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol 2006;4:936-62. 3. Lok AS, Macmohan BJ. Chronic hepatitis B. Hepatol 2007; 45:507-39. 4. Hoofnagle JH, Doo E, Liang J, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatol 2007;45:1056-75. 5. Lok ASF. Navigating the maze of hepatitis B treatment. Gastroenterology 2007;132:1586-94. 6. Lia CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. Ann Intern Med 2007;147:58-61.

■■■■

Cord Colitis a Novel Infection? A newly-discovered type of bacteria was identified as a possible perpetrator in colitis that develops after cordblood stem cell transplantation. Genetic sequencing of colon biopsies from patients with cord colitis syndrome turned up a novel genome most closely related to that of a symbiotic, nitrogen-fixing bacteria used extensively in commercial agriculture. The new bacterium - provisionally named Bradyrhizobium enterica - was confirmed as present in all three additional cord colitis cases at a single center, but in no healthy controls or patients with colon cancer or graftversus- host disease, the researchers reported in the Aug. 8 issue of the New England Journal of Medicine. “Association of these sequences with cord colitis suggests that B. enterica may be an opportunistic human pathogen,” they suggested. However, they cautioned “that although we have suggested a possible association between B. enterica and cord colitis, we have not shown that the association is the cause or the consequence of the clinical syndrome, nor have we shown the generalizability of the association in patients other than those in the original, single-institution cohort.” No bradyrhizobium species have previously been associated with disease in humans.

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Internal medicine

Clinical and Laboratory Evaluation of Patients with Fever with Thrombocytopenia Shankar R Raikar*, Panna K Kamdar**, Ajay S Dabhi**

Abstract Aims: To evaluate clinical profile of fever with thrombocytopenia. To identify the causes of fever with thrombocytopenia. To assess the clinical complications associated with fever and thrombocytopenia. Material and methods: This study was done on patients, who were admitted to Sir T. Hospital and Government Medical College, Bhavnagar, Gujarat. We prospectively collected a series of 100 patients with fever and thrombocytopenia. Results: Age and sex distribution; In this study male out numbered female. Platelet count and bleeding; Of 100 patients four had bleeding manifestations. There is no correlation between platelet count and bleeding. Degree of thrombocytopenia in various diseases; (1) Viremia; Among infectious cases viremia including dengue accounted for the vast majority. In this study out of 100 cases viremia including dengue accounts for 52 cases. (2) Dengue; In our study dengue caused severe thrombocytopenia. Twenty patients out of 40 cases had count <50,000/mm3. (3) Malaria; In our study malaria caused mild-to-moderate thrombocytopenia with counts remaining between 50,000 to 1 lacs in most cases. Bleeding manifestations; In our study, out of 100 patients only four patients presented with bleeding manifestations. Three patients of mixed Plasmodium vivax with Plasmodium falciparum malaria presented with petechie, purpura and hematuria. One patient of dengue presented with gum bleeding. Platelet count and fever; In this study, shortest duration of fever is three days and longest is 10 days. Platelet count started increasing from 2nd day of admission to 8th day of admission with relative treatment. Enteric fever; In our study out of 100 patients three had fever with thrombocytopenia without any bleeding manifestations.

Keywords: Dengue, malaria, viremia, enteric fever, hematuria

F

ever is a pervasive and ubiquitous theme in human myth, art and science. Fever is such a common manifestation of illness that it is not surprising to find. New interest surfaced in the relationship between body temperature and disease. Initially thought to be a product of polymorphonuclear leukocyte, this endogenous pyrogen is generated by mononuclear phagocytes. It is identical or very similar in composition to substances previously identified as lymphocyte activating factor (LAF), mononuclear cell factor and leukocyte endogenous mediator collectively known as interleukin-1 (IL-1). IL-1 has now been shown to have a major role in thermoregulation.

AIMS AND OBJECTIVES ÂÂ

To evaluate clinical thrombocytopenia.

profile

ÂÂ

To identify the thrombocytopenia.

ÂÂ

To assess the complications associated with fever and thrombocytopenia.

cause

of of

fever fever

with with

MATERIAL AND METHODs This study was done on patients, who were admitted to Sir T Hospital and Government Medical College, Bhavnagar, Gujarat. We prospectively collected a series of 100 patients with fever and thrombocytopenia.

Inclusion Criteria

*Senior Resident **Associate Professor Dept. of Medicine Medical College and Sir T Hospital, Bhavnagar, Gujarat Address for correspondence Dr Ajay S Dabhi 38, Alka Nagar, Near Priyalaxmi Mill, Old Alembic Road, Vadodra - 390 003, Gujarat E-mail: dr_ajay_44@yahoo.co.in

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

The patients of both sexes aged >12 years. Patients admitted with fever and found to have thrombocytopenia are included in the study.

Exclusion Criteria Patients <12 years are excluded. Patients with fever and no thrombocytopenia are not included. Patients with thrombocytopenia and no fever are not included.


Internal medicine Table 1. Distribution of Disease Age

Male

Female

Table 2. Sex-wise Distribution of Cases Disease

Total

Disease

37%

15%

52%

Male (%) Female (%)

Total (%)

12-30 years

29

11

Dengue

40

Dengue

30-45 years

6

2

Dengue

8

P. vivax malaria

16%

5%

21%

45-60 years

2

1

Dengue

3

P. falci malaria

15%

6%

21%

>60 years

0

0

Dengue

0

P. vivax + P. falci malaria

3%

0%

3%

12-30 years

12

1

P. vivax

13

Enteric fever

2%

1%

3%

30-45 years

2

3

P. vivax

5

45-60 years

2

1

P. vivax

3

>60 years

0

0

P. vivax

0

12-30 years

8

2

P. falci

10

30-45 years

3

1

P. falci

4

45-60 years

2

1

P. falci

3

>60 years

2

2

P. falci

4

12-30 years

1

1

Enteric fever

2

30-45 years

1

0

Enteric fever

1

45-60 years

0

0

Enteric fever

0

>60 years

0

0

Enteric fever

0

12-30 years

1

0

P. vivax + falci

1

30-45 years

1

0

P. vivax + falci

1 1

45-60 years

1

0

P. vivax + falci

Method Once the patients admitted with fever and those who had thrombocytopenia, a careful history was recorded, general physical examination was done. Detailed examination of various systems was done. Routine investigation was done, the specific and special investigations were done as and when indicated. In whom a final definite diagnosis was reached, were treated for the disease and platelet, count was repeated at the time of discharge. Details of history, general physical examination and laboratory and technical investigation reports were noted down from time to time. Once the specific diagnosis was reached, patients were treated for it specifically and symptomatically. Results In our study, out of 100 patients 52 are having Dengue (37 M, 15 F), 21 patients are having Plasmodium vivax

Table 3. Sex-wise Platelet Count Disease

Lowest platelet count in male

Lowest platelet count in female

Dengue

10,000

13,000

P. vivax malaria

28,000

20,000

P. falci malaria

12,000

25,000

Enteric fever

90,000

50,000

Table 4. Relationship between Day of Fever and Platelet Count Disease

Lowest platelet count/Day of admission our study

Normal platelet count/Day of admission our study

Dengue

1-2

4-5

P. vivax malaria

1-2

4-5

P. falci malaria

1-3

4-7

Enteric fever

1-2

4-5

Table 5. Relation of Month of Year and Number of Cases for Each Disease Disease

October 2010/No. of cases

November 2010/No. of cases

December 2010/No. of cases

Dengue

10

22

20

Malaria

12

18

12

Enteric fever

02

01

00

malaria (16 M, 5 F), 21 patients are having Plasmodium falciparum malaria (15 M, 6 F), three male patients having mixed P. vivax and P. falciparum malaria, three patients having enteric fever (2 M, 1 F) (Table 1).

Age and Sex Distribution In our study, male are affected more than female. Young aged male (12-30 years) are affected more than young age female (12-30 years) (Table 2).

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Internal medicine Table 6. Relation of season to Number of Cases for Each Disease

Degree of Thrombocytopenia in Various Diseases

Disease

Study proper/season

Dengue

Rainy/Winter

Malaria

Rainy/Winter

In our study, Dengue is the commonest cause. Lowest platelet count in each disease and its relation to male and female is shown in Table 3.

Enteric fever

Rainy/Winter

Relation Between Day of Fever and Platelet Count In our study, low platelet count seen on the day of admission, which started raising from Day 3 to 4, and reached to normal value on average of 4 to 7 days of admission (Table 4).

60 50 40

Series 1 Column 1

30

Relation of Season (Month of Year) and Number of Cases for Each Disease In our study, maximum number of cases of fever with thrombocytopenia are seen mainly during rainy and early winter season (Tables 5 and 6).

20 10 0

Dengue

P. vivax

P. falci

P. vivax + falci

Enteric

CONCLUSION ÂÂ

Febrile illness accounts for large number of cases with thrombocytopenia. Incidence is more in male compared to females. Maximum prevalence is in the younger age group, 66% of cases seen in 12-30 years age group. Least prevalence seen in elderly age group, 10%. Fever is the presenting complaint in all 100 cases. Bleeding manifestations were very rarely seen in our study.

ÂÂ

Patients who had hematuria had relatively low platelet count, <20,000/mm3. Viremia is the commonest cause of thrombocytopenia in our study including Dengue, 52% of cases. Bleeding time has no relation to platelet count or bleeding manifestation. No mortality was seen in our study. P. vivax malaria accounts 22% of cases and P. falciparum malaria 21% of cases. Mixed infection that is combined P. vivax and P. falciparum malaria accounted for 3% of cases. Bacterial infection in our study is mainly seen with enteric fever. Enteric fever accounts for 3% of cases of fever with thrombocytopenia. Thrombocytopenia due to infectious diseases shows seasonal variation, commonly seen in rainy and winter season.

Figure 1. Distribution of disease. 40 35 30 Male Female

25 20 15 10 5 0

Dengue

P. vivax

P. falci

P. vivax + falci

Enteric

Figure 2. Male and female distribution of disease. 25 20

October November December

15

SUMMARY

10

ÂÂ

Thrombocytopenia is hematological entity.

ÂÂ

Viremia accounts for most cases.

ÂÂ

Platelet count should be asked in cases with fever.

ÂÂ

Thrombocytopenia has no correlation to mortality

5 0

Dengue

Malaria

Enteric

Figure 3. Seasonal distribution of disease.

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

a

commonly

observed


Internal medicine and morbidity. ÂÂ

There is no relation between platelet count and bleeding manifestations.

ÂÂ

The condition in which thrombocytopenia develops has an important influence on bleeding when associated with infection or uremia, bleeding can occur even with mildly reduced counts as additional functional defects contribute.

ÂÂ

Thrombocytopenia due to infectious diseases shows seasonal variation, commonly seen in rainy and winter season.

Suggested Reading 1. Machin SJ. Oxford text of Medicine. 3rd edition, Volume 3 p.3630-6. 2. Shirley Parker Levine Wintrobe’s Clinical Haematology. 10th edition, Volume 2 1993:p.1579-632. 3. Colman W, Hirsch J, Marder VJ, Salzman EW. Hemostansis and Thrombosis - Basic Principles and Clinical Practice. 1982:p.146-7. 4. William-J-William. Eaenst Beutler, Allan J Erslev, Marshal and Litchman Hematology. 3rd edition p.1290-342.

5. Firkin F. de Gruchy’s Clinical Haematology in Medical Practice. 5th edition 1990:p.375. 6. Robbin and Cotran Pathologic Basis of Disease. 7th edition 2000:p.650. 7. Shirley Parker Levine Wintrobe’s Clinical Haematology. 10th edition, Volume 2 1993:p.1581. 8. Bizzaro N. EDTA-dependent pseudothrombocytopenia: a clinical and epidemiological study of 112 cases, with 10-year follow-up. Am J Hematol 1995;50(2):103-9. 9. Imbach P, Kühne T, Signer E. Historical aspects and present knowledge of idiopathic thrombocytopenic purpura. Br J Haematol 2002;119(4):894-900. 10. George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1994;331(18):1207-11. 11. Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991;77(1):31-3. 12. Nieminen U, Kekomäki R. Quinidine-induced thrombocytopenic purpura: clinical presentation in relation to drug-dependent and drug-independent platelet antibodies. Br J Haematol 1992;80(1):77-82.

■■■■

A novel use of ultrasound as a therapy in the brain rather than diagnostic has been reported by lead author W. Jeffrey Elias, MD, associate professor, neurosurgery, University of Virginia, Charlottesville. In a small pilot study, thalamotomy using high-intensity focused ultrasound, guided by MRI, improved tremor, particularly in the hand, and quality-of-life in patients with essential tremor. Results of the phase 1 open–label uncontrolled trial are published in the August 15 issue of the New England Journal of Medicine. (Source: Medscape) ________________________________________________________________________ Severe psychiatric illness, especially schizophrenia and major depression, are associated with an increased risk for death, but the newer agents prescribed to treat these illnesses appear to reduce this risk. The results are from an analysis of US Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports comprising more than 92,000 patients with psychiatric illness. ________________________________________________________________________ Most women whose prenatal and childbirth care are led by a midwife have better outcomes compared with those whose care is led by a physician or shared among disciplines, according to a systematic review of 13 trials involving 16,242 women published August 22 in the Cochrane Database of Systematic Reviews. (Source: Medscape)

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Neurology

Communication Between Musculocutaneous and Median Nerve – Different Types and Their Incidence in North Indian Population Priti Chaudhary*, gurdeep Kalsey**, ranjan Singla†, kamal Arora‡

Abstract The variations of the median nerve and the musculocutaneous nerve, like the communication between the two, may prove valuable in the traumatology of the shoulder joint and the upper arm region and in situations when the surgeon has to isolate and trace the median and musculocutaneous nerve distally. The present study was conducted on 60 upper limbs belonging to 30 cadavers (Male:Female = 28:02), (Right:Left = 30:30) obtained from Dept. of Anatomy, Govt. Medical College, Amritsar, Punjab. Brachial plexuses were exposed as per standard guidelines. The observations recorded were as follows: 1). The musculocutaneous nerve was absent in six (10%) limbs; the muscles usually supplied by this being supplied by median nerve in two limbs and by lateral cord (coracobrachialis) and median nerve (biceps and brachialis) in the other four limbs. 2). A single communication between the musculocutaneous and the median nerve was encountered in the six (10%) limbs. It was in the upper third of the upper arm, proximal to the entrance of the musculocutaneous nerve into the coracobrachialis muscle. 3.) A complete fusion of the musculocutaneous nerve and the median nerve after normal formation of the former was seen in four (6.66%) limbs. Out of these four limbs; in 1 limb, coracobrachialis; in 2 limbs, coracobrachialis and biceps and in one limb all three muscles of the anterior compartment were supplied by musculocutaneous nerve before its fusion with the median nerve.

Keywords: Brachial plexus, communication, lateral cord, median nerve, musculocutaneous nerve

B

rachial plexus is a network of nerves supplying the upper limb with the root value C5-T1. These roots join with each other to form three trunks viz; the upper, middle and lower by union of C5, C6; continuation of C7 and union of the C8 and T1, respectively. The three trunks bifurcate into anterior and posterior divisions. The anterior divisions of the upper and middle trunks unite to form the lateral cord. The anterior division of the lower trunk continues as the medial cord. The posterior divisions of all the three trunks unite to form posterior cord. These cords give rise to different nerves for the upper limb.

*Assistant Professor Dept. of Anatomy, GGS Medical College, Faridkot, Punjab **Professor and Head †Associate Professor Dept. of Anatomy, Govt. Medical College, Amritsar, Punjab ‡Medical Officer, Civil Hospital, Ferozepur, Punjab Address for correspondence Dr Priti Chaudhary, MS Anatomy Assistant Professor, Dept. of Anatomy GGS Medical College, Faridkot, Punjab E-mail: pritiarorafdk@rediffmail.com

ÂÂ

Musculocutaneous nerve is one of the terminal branches of lateral cord and supplies the muscles of anterior compartment of arm i.e., coracobrachialis, biceps brachii and brachialis.

ÂÂ

Median nerve is formed by the union of lateral and medial roots (branches of lateral and medial cords, respectively) and supplies most of the muscles of flexor compartment of forearm. It gives no muscular branch to muscles of the arm.

Variations in the origin of the median and musculocutaneous nerve are quite common. The commonest amongst these is the absence of musculocutaneous nerve with innervation of coracobrachialis, biceps brachii and brachialis by median nerve [Li Minor, (1992); Rao and Chaudhry, (2000); Sud and Sharma, (2000); Rajashree et al, (2003) and Saritha, (2004)]. Another variation is communication between musculocutaneous nerve and median nerve. Venieratos and Anangnostopoulou (1998) believed it to be the most frequent variant of this nerve where some fibers of the lateral root of the median nerve run along with the musculocutaneous nerve and after traveling some distance, leave the latter to join the ultimate destination (the median nerve). We observed all these variations in

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Neurology the different limbs along with the four cases of complete fusion of musculocutaneous nerve and median nerve during a study, perfomed on 60 upper limbs. Aim of the study was to describe the exact topography of these variations and to discuss their development and clinical significance. MATERIAL AND METHODS The material for the present study comprised of 60 upper limbs belonging to 30 adult human cadavers of known sex (Male:Female = 28:02) obtained from the Dept. of Anatomy, Govt. Medical College, Amritsar, Punjab. These were serialized from 1 to 30 with suffix ‘M’ for male or ‘F’ for female and ‘R’ for right or ‘L’ for left. The brachial plexus was dissected and exposed according to the methods described by Romanes (1995) in Cunningham’s Manual of Practical Anatomy. All its roots, trunks, divisions, cords and branches were cleaned and the pattern of the formation and branching was seen. For measuring the lengths of different parts of brachial plexus, a thread was kept along the length of that part and was marked with Indian ink at designated points. The thread thus marked was lifted off the dissection area, and spread along a graduated metric scale to measure the length. All the measurements were taken in centimeters. OBSERVATIONS Out of 60 upper limbs dissected, following variant patterns of musculocutaneous and median nerves were observed:

Absence of the Musculocutaneous Nerve Musculocutaneous nerve was seen coming as one of the terminal branches of the lateral cord in 54 (90.00%) limbs of the present study being absent in rest of the six (10.00%) limbs (i.e., limb no. 4 MR, 4 ML, 9 MR, 9 ML, 11 ML, 13 MR). Out of these six limbs in which it was absent, 4 belonged to two cadavers i.e., it was bilaterally absent in two bodies and unilaterally absent in another two bodies (See below). ÂÂ

In two limbs viz; limb no. 9 MR and 9 ML all the three muscles viz; coracobrachialis, biceps brachii and brachialis, which are usually supplied by musculocutaneous nerve, were supplied by the median nerve.

ÂÂ

In four (6.66%) limbs viz; limb no. 4 MR, 4 ML, 11 ML, 13 MR, there was absence of the musculocutaneous nerve with the innervation of the coracobrachialis from the branches of the lateral cord and of biceps and brachialis by the median nerve. Out of these four limbs, it was seen bilaterally in 4 M (R and L) (Fig. 1).

Communication Between Musculocutaneous and Median Nerve A single communication between the musculocutaneous and the median nerve was encountered in the six (10%) limbs i.e., limb no. 18 MR, 18 ML, 23 ML, 24 MR, 25 ML and 27 MR. In all the limbs, it was in the upper third of the upper arm, proximal to the entrance of the musculocutaneous nerve into the coracobrachialis muscle (Fig. 2). Table 1 shows the length of communicating branch and its distance from point of formation of musculocutaneous and median nerve.

Table 1. Showing Length of the Communicating Branch (CB) and its Distance from the Origin of Musculocutaneous Nerve and Median Nerve

Limb no.

Distance between point of formation of the MCN and of CB (cm)

Distance between point of formation of MN and point of joining of CB with it (cm)

Length of CB (cm)

18 ML

4.5

4.3

3.9

18 MR

3.6

9.3

5.2

23 ML

2.4

2.2

3.2

24 MR

1.9

5.0

4.7

25 ML

2.6

3.0

2.5

27 MR

2.9

7.5

6.3

Mean

2.98

5.21

4.3

CB = Communicating branch; MCN = Musculocutaneous nerve; MN = Median nerve.

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Neurology

Figure 1. Showing the absence of musculocutaneous nerve in limb no. 4 MR with lateral cord (LC) giving a branch (BCB) to coracobrachialis (CB) and continuing as lateral root of median nerve (LR). Median nerve (MN) gives a muscular branch (MB) to supply biceps brachii (BB) and brachialis: BBr = Branch to brachialis MR = Medial root; UN = Ulnar nerve.

Figure 3. Showing complete fusion of musculocutaneous nerve (MCN) with the median nerve (MN) in limb no. 1 MR after the former pierces and supply the coracobrachialis muscle (CB). UN = Ulnar nerve; LR and MR = Lateral and medial roots of median nerve.

It is evident from the Table 1, that the communicating branch was given off at an average distance of 2.98 cm (range 1.9-4.5 cm) from the point of origin of the musculocutaneous nerve and joined the median nerve at an average distance of 5.21 cm (range 2.2-9.3 cm) from the latterâ&#x20AC;&#x2122;s formation. Its own average length was 4.3 cm (range 2.5-6.3 cm).

Complete Fusion of the Musculocutaneous and the Median Nerve

Figure 2. Showing the communicating ramus (CR) from the musculocutaneous nerve (MCN) to median nerve (MN) in limb no. 23 ML LC and MC = Lateral and medial cords; LR and MR = Lateral and medial roots of median nerve; UN = Ulnar nerve; CB = Coracobrachialis muscle.

It was seen in four (06.66%) limbs i.e., limb no. 1 MR, 2 MR, 7 ML and 21 ML. Out of these, in three limbs (1 MR, 7 ML and 21 ML), the other terminal branch of the lateral cord i.e., the lateral root of the median nerve was very thin and the most of the fibers of the lateral cord contributed to the formation of the musculocutaneous nerve, which however joined the median nerve at an average distance of 10.06 cm from the formation of the latter. In the fourth limb (limb no. 2 MR), the lateral root of the median nerve was normal in diameter and musculocutaneous nerve joined with the median nerve at a distance of 7.5 cm from the formation of the median nerve. In the limb no. 1 MR, coracobrachialis muscle was supplied by the musculocutaneous nerve and the biceps brachii and brachialis by the median nerve (Fig. 3).

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Neurology In the limb no. 2 MR and 7 ML, the coracobrachialis and the biceps brachii were supplied by the musculocutaneous nerve and brachialis by the median nerve.

Table 2. Showing the Incidence of Communication between the Musculocutaneous Nerve and the Median Nerve Author

Year

Incidence

In the limb no. 21 ML, the musculocutaneous nerve joined with the median nerve after supplying all the muscles of the anterior compartment of the arm i.e., coracobrachialis, biceps brachii and the brachialis.

Watanabe et al

1985

01.4%

Kosugi et al

1986

21.8%

Yang et al

1995

12.5%

Eglseder and Goldman

1997

36.0%

DISCUSSION

Venieratos and Anagnostopoulou

1998

13.9%

Absence of the Musculocutaneous Nerve

Chiarapattanakom et al

1998

16.0%

Rao and Chaudhary

2000

33.3%

Aktan et al

2000

10.4%

Choi et al

2002

26.4%

Present study

2005

10.0%

In the present study, it was absent in six (10%) limbs. ÂÂ

ÂÂ

In two (3.33%) limbs, all the three muscles viz; coracobrachialis, biceps brachii and brachialis were supplied by the median nerve. Similar situation had been earlier encountered by Broca (1888); Kerr (1918); Li Minor, (1992); Rao and Chaudhry, (2000); Sud and Sharma, (2000); Rajashree et al, (2003) and Saritha, (2004). While Broca (1888) gave its incidence range as 0.3-2.0%, Kerr (1918) could not trace musculocutaneous nerve in 5.14% of his 175 dissections with all muscles being supplied by the median nerve. Rest of the authors have reported only the single cases of this variant. In four (6.66%) limbs, there was absence of the musculocutaneous nerve with the innervation of the coracobrachialis from the branches of the lateral cord and of biceps and brachialis by the median nerve. Earlier Gumusburun and Adiguzel (2000) also came across the same variation, being bilateral, during the dissection of a 72-year-old female cadaver. However, Abhaya et al (2003 b) while reporting a similar case as that of Gumusburun and Adiguzel (2000) named it a dual origin of the musculocutaneous nerve, one from the lateral cord and the other from the median nerve.

Communication Between Musculocutaneous and Median Nerve Another variation noted in the musculocutaneous nerve was its communication with the median nerve encountered in six (10.00%) limbs of the present study. Venieratos and Anangnostopoulou (1998) believed it to be the most frequent variant of this nerve, where some fibers of the lateral root of the median nerve run along with the musculocutaneous nerve and after traveling some distance, leave the latter to join the ultimate destination (the median nerve) thus giving the appearance as if there are two lateral roots of the median nerve.

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Its incidence has been variously reported by the earlier workers and compared with the present study in the Table 2. The communication between the musculocutaneous and the median nerve have been classified in different types by Li Minor (1992), Venieratos and Anagnostopoulou (1998) and Choi et al (2002). Li Minor, (1992) categorized these communications into following five type: ÂÂ Type I: There is no communication between the median nerve and the musculocutaneous nerve. ÂÂ Type II: The fibers of the lateral root of the median nerve pass through the musculocutaneous nerve and join the median nerve in the middle of the arm. ÂÂ Type III: The lateral root fibers of the median nerve pass along the musculocutaneous nerve and after some distance, leave it to form the lateral root of the median nerve. ÂÂ Type IV: The musculocutaneous fibers join the lateral root of the median nerve and after some distance the musculocutaneous nerve arises from the median nerve. ÂÂ Type V: The musculocutaneous nerve is absent and the entire fibers of the musculocutaneous nerve pass through the lateral root and fibers to the muscles supplied by the musculocutaneous nerve branch out directly from the median nerve. Similarly based upon its site with relation to the coracobrachialis muscle Venierators and Anagnostopoulou, (2000) classified this communication into three types: ÂÂ Type I: The communication is proximal to the entrance of the musculocutaneous nerve into the coracobrachialis muscle.


Neurology Table 3. Showing the Comparison of Lengths of the Communicating Branch (CB) and Its Distance from the Origin of Musculocutaneous and Median Nerve Author (year)

Total no. of No. of limbs having the Average distance the limbs communication (%) between point of studied formation of the MCN and of CB (cm)

Average distance between point of formation of the MN and point of joining of CB with it (cm)

Mean length of CB (cm)

Rao and Chaudhary (2000)

24

08 (33.33%)

15.5

Not reported

8.95

Aktan et al (2000)

48

05 (10.40%)

0.95 ± 0.42

10.25 ± 2.32

5.50

Present study (2005)

60

06 (10.00%)

2.98

5.21

4.3

CB = Communicating branch; MCN = Musculocutaneous nerve; MN = Median nerve ÂÂ

Type II: The communicating branch arises distal to the coracobrachialis muscle from the musculocutaneous nerve.

ÂÂ

Type III: The musculocutaneous nerve and the communicating branch do not pierce the coracobrachialis muscle.

Later on Choi et al (2002) in a study on 138 cadavers classified these communications into three types: ÂÂ

Pattern 1: Fusion of both nerves (19.2%)

ÂÂ

Pattern 2: Presence of one supplementary branch between both nerves (72.6%).

ÂÂ

zz

Pattern 2a: Single root from musculocutaneous nerve, contributes to the connection (69.9%).

zz

Pattern 2b: There are two roots musculocutaneous nerve (2.7%).

from

Pattern 3: Presence of two branches between both nerves (6.8%).

All our limbs fit into type II of Li Minor (1992), type I of Venieratos and Anagnostopoulou (1998) or into type II (2a) of Choi et al (2002). According to Bergman et al (1988) the communicating branch usually joins the median nerve in the lower third of the upper arm. If it joins the median nerve in the upper third of the upper arm, it is generally considered as the third (double lateral) root of the median nerve. Since in the present study, in all the six limbs it was observed in the upper third of the upper arm, it can be considered as the double lateral root of the median nerve or in other words the median nerve can be said to be formed by three roots: (a) One from the lateral cord; (b) one from the musculocutaneous nerve and (c) the third from the medial cord. Similar variation was observed earlier by different authors - The median nerve, instead of having two roots may have three roots - either one each from

lateral cord, medial cord and musculocutaneous nerve (Chauhan and Roy, 2002; Saritha, 2004) or two from lateral cord and one from the medial cord (Sargon et al, 1995; Mohapatra et al, 2004) or it may have even four roots - three from the lateral cord and one from the medial cord (Uzun and Seelig, 2001). Table 3 compares the lengths of communicating branch and its distance from origin of musculocutaneous and median nerve with the earlier studies. It is evident from Table 3 that there is a lot of difference in the various distances of communicating branch. Whereas, it originated at an average distance of 2.98 cm from the point of formation of the musculocutaneous nerve in the present study. Rao and Chaudhary (2000) found it at a distance of 15.5 cm and Aktan et al (2000) at a distance of 0.95 ± 0.42 cm. Similarly, the other distances are also quite variable in the three studies.

Complete Fusion of the Musculocutaneous and the Median Nerve It was seen in four (6.66%) limbs in the present study. Earlier Lang and Spinner, (1970) reported a complete fusion of the median and the musculocutaneous nerve. Similarly Watanabe et al, (1985) found two cases (1.4%) of fusion of musculocutaneous and median nerves among 140 upper limbs and Yang et al (1995) encountered one such case out of 24 cadaveric specimens (4%).

Ontogeny The presence of the communications may be attributed to the random factors influencing the mechanism of formation of the limb muscles and the peripheral nerves during the embryonic life. Significant variations in the nerve patterns may be a result of the altered signalling between the mesenchymal cells and neuronal growth cones and once formed antenatally persist postnatally

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Neurology (Sannes et al, 2000; Abhay et al, 2003) or these may be due to circulatory factors at the time of fusion of the brachial plexus cords (Kosugi et al, 1986). Iwata (1960) believed that the human brachial plexus appears as a single radicular cone in the upper limb bud, which divides longitudinally into ventral and the dorsal segments. The ventral segments give roots to the median and the ulnar nerves with musculocutaneous nerve arising from the median nerve. He further kept the possibility of failure of the differentiation as a cause for some of the fibers taking an aberrant course as a communicating branch. Chiarapattanakom et al (1998) are of the opinion that the limb muscles develop from the mesenchyme of local origin, while axons of spinal nerves grow distally to reach the muscles and/or skin. They blamed the lack of coordination between the formation of the limb muscles and their innervation for appearance of a communicating branch.

Phylogeny Chauhan and Roy (2002) strongly recommend the consideration of the phylogeny and the development of the nerves of the upper limb for the interpretation of the nerve anomalies of the arm. Considering the communication between the musculocutaneous and the median nerve as a remnant from the phylogenetic or comparative anatomical point of view and that the ontogeny recapitulates the phylogeny, they feel that the variations seen are the result of the developmental anomaly. In the lower vertebrates of the Artiodactyla and Perissodactyla (amphibians, reptiles and birds) there is only one nerve i.e. median nerve supplying the muscles of the upper arm and an independent musculocutaneous nerve is absent (Sisson and Grossman, 1961; Arlamowska â&#x20AC;&#x201C; Palider, 1970). Similar was the situation in both limbs of cadaver no. 9 of our study, which thus represents these vertebrates. Similarly in dogs, the musculocutaneous nerve sends a communicating branch to the median nerve (Sisson and Grossman, 1961; Miller, 1932) as seen in the limb no. 18 ML, 18 MR, 23 ML, 24 MR, 25 ML, 27 MR of the present study.

Clinical Significance Rao and Chaudhary (2000) emphasized upon the value of the knowledge of communicating branch between the musculocutaneous and the median nerve in traumatology of the shoulder and/or the upper arm region and in situations when the surgeon has to isolate

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

and trace the median and/or musculocutaneous nerve distally. They also correlated such communications to the entrapment syndromes of the musculocutaneous nerve in which a part of the median nerve also passes through the coracobrachialis muscle exhibiting the signs and symptoms similar to those encountered in the median nerve neuropathy as in the carpal tunnel syndrome or the pronator syndrome. Knowledge of the communicating branch may be useful for clinicians thereby avoiding unnecessary carpal tunnel release in such cases. Sunderland (1978) is of the opinion that the lesions of the communicating nerve may give rise to the patterns of weakness that may impose difficulty in the diagnosis. Further an injury to the musculocutaneous nerve proximal to the anastomotic branch between the musculocutaneous nerve and the median nerve may lead to the unexpected presentation of weakness of the forearm flexors and the thenar muscles. Choi et al (2002) stressed upon the significance of these communicating branches in diagnostic clinical neurophysiology. Leffert (1985) emphasized to rule out such communications to prevent the unwanted outcomes of operations conducted on the musculocutaneous nerve. SUMMARY and CONCLUSION The musculocutaneous nerve was seen coming as one of the terminal branches of the lateral cord in 54 (90.00%) limbs of the present study, being absent in rest of the six (10.00%) limbs (bilaterally absent in 2 bodies and unilaterally absent in another 2 bodies) and all the three muscles viz; coracobrachialis, biceps brachii and brachialis, which are usually supplied by musculocutaneous nerve, were supplied by the median nerve in two limbs while in the other four limbs, coracobrachialis was supplied by the branches of the lateral cord and biceps and brachialis by the median nerve. Another variation noted in the musculocutaneous nerve was its communication with the median nerve encountered in six (10.00%) limbs in the upper third of the upper arm; thus giving the appearance of the double lateral root of the median nerve or in other words the median nerve being formed by three roots: (a) One from the lateral cord; (b) one from the musculocutaneous nerve and (c) the third from the medial cord. The communicating branch was given off at an average distance of 2.98 cm (range 1.9-4.5 cm) from the point of origin of the musculocutaneous nerve and joined the median nerve at an average distance of 5.21 cm (range 2.2-9.3 cm) from the latterâ&#x20AC;&#x2122;s formation.


Neurology Its own average length was 4.3 cm (range 2.5-6.3 cm). In four (06.66%) limbs, the musculocutaneous nerve after supplying some of the muscles of the anterior compartment of the arm fused with the median nerve. Out of these in one, it supplied the coracobrachialis; in two: Coracobrachialis and biceps and in the fourth coracobrachialis, biceps and brachialis before joining the median nerve. All the variations of the musculocutaneous nerve have been explained ontogenically. The presence of the communications may be attributed to the random factors influencing the mechanism of formation of the limb muscles and the peripheral nerves during the embryonic life - may be as a result of the altered signalling between the mesenchymal cells and neuronal growth cones OR failure of the differentiation as a cause for some of the fibers taking an aberrant course as a communicating branch OR lack of coordination between the formation of limb muscles and their innervation has been held responsible for the development of a communicating branch. Phylogenetically the limbs with no musculocutaneous nerve are equated with amphibians, reptiles and birds and limbs with the communicating branch between the musculocutaneous and the median nerve are equated with dogs thus supporting the dictum, ‘ontogeny recapitulates phylogeny’. Further, the clinical implications of these variations of the musculocutaneous nerve are discussed. Suggested Reading 1. Abhaya A, Bhardwaj R, Prakash R. Dual origin of musculocutaneous nerve. J Anat Soc India 2003a;52(1):94. 2. Abhaya A, Khanna J, Prakash R. Variation of the lateral cord of brachial plexus piercing coracobrachialis muscle. J Anat Soc India 2003b;52(2):168-70. 3. Aktan ZA, Ozturk L, Bilge O, Ozer MA, Pinar YA. A cadaveric study of the anatomic variations of the brachial plexus nerves in the axillary region and arm. Turk J Med Sci 2000; 31:147-50. 4. Arlamowska-Palider A. Comparative anatomical studies of nervus musculocutaneous in mammals. Acta Theriol. XV. 1970;22: 343-56. Cited by Prasada Rao PV, Chaudhary SC. Communication of the musculocutaneous nerve with the median nerve. East Afr Med J 2000;77(9):498-503. 5. Bergman RA, Afifi AK, Miyauchi R. Illustrated encyclopedia of human anatomic variation. In: Nervous System – Plexuses. Website: virtualhospital.com.university of iowa care, 1988. 6. Broca (1888). Cited by Gümüsburun E, Adigüzel E. A variation of the brachial plexus characterized by the absence of the musculocutaneous nerve: a case report. Surg Radiol Anat 2000;22(1):63-5.

7. Chauhan R, Roy TS. Communication between the median and musculocutaneous nerve: a case report. J Anat Soc India 2002;51(1):72-5. 8. Chiarapattanakom P, Leechavengvongs S, Witoonchart K, Uerpairojkit C, Thuvasethakul P. Anatomy and internal topography of the musculocutaneous nerve: the nerves to the biceps and brachialis muscle. J Hand Surg Am 1998;23(2):250-5. 9. Choi D, Rodríguez-Niedenführ M, Vázquez T, Parkin I, Sañudo JR. Patterns of connections between the musculocutaneous and median nerves in the axilla and arm. Clin Anat 2002;15(1):11-7. 10. Eglseder WA Jr, Goldman M. Anatomic variations of the musculocutaneous nerve in the arm. Am J Orthop (Belle Mead NJ) 1997;26(11):777-80. 11. Gumusburun E, Adiguzel E. A variation of the brachial plexus characterized by the absence of musculocutaneous nerve: a case report. Surg Radiol Anat 2000;22(1) 63-5. 12. Iwata H. Studies on the development of the brachial plexus in Japanese embryo. Rep Dept Anat Mie Prefect Univ Sch Med 1960;13:129-144. Cited by Prasada Rao PV, Chaudhary SC. Communication of the musculocutaneous nerve with the median nerve. East Afr Med J 2000;77(9):498-503. 13. Kerr AT. The brachial plexus of nerves in man, the variations in its formation and branches. Am J Anat 1918; 23(2):285-395. 14. Kosugi K, Mortia T, Yamashita H. Branching pattern of musculocutaneous nerve. 1. Cases possessing normal biceps brachii. Jikeakai Med J 1986;33:63-71. 15. Lang J, Spinner M. An important variation of the brachial plexus--complete fusion of the median and musculocutaneous nerves. Bull Hosp Joint Dis 1970;31(1): 7-13. 16. Leffert RD. Brachial plexus injuries. In: Anatomy of the Brachial Plexus. Churchill Livingstone: New York 1985:p.384. 17. Le Minor JM. A rare variation of the median and musculocutaneous nerves in man. Arch Anat Histol Embryol 1990;73:33-42. 18. Miller RA. Comparative studies upon the morphology and distribution of the brachial plexus. Am J Anat 1932; 54(1):143-66. 19. Mohapatra BB, Chinara PK, Dutta BK, Nayak AK. Variation in the formation and branching pattern of median nerve. J Anat Soc Ind 2004;53(1):31-66. 20. Rajashree B, Arati D, Mamata S, Chinmayi M, Charulata S. Absence of musculocutaneous nerve - a case report. J Anat Soc India 2003;52(1):94. 21. Prasada Rao PV, Chaudhary SC. Communication of the musculocutaneous nerve with the median nerve. East Afr Med J 2000;77(9):498-503. 22. Romanes GJ. The pectoral region & axilla and side of the neck. In: Cunningham’s Manual of Practical Anatomy. 15th edition, Vol. 1 & 3. The English Language Book Society and Oxford University Press: Edinburgh, London 1995p.26-8, 28-34 resp.

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Neurology 23. Sannes HD, Reh TA, Harris WA. Axon growth and guidance. In: Development of Nervous System. Academic Press: New York 2000:p.189-97. 24. Sargon MF, Uslu SS, Celik HH, Akşit D. A variation of the median nerve at the level of brachial plexus. Bull Assoc Anat (Nancy) 1995;79(246):25-6. 25. Saritha S. Variations in the median and musculocutaneous nerves-A surgical prospective. J Anat Soc Ind 2004; 53(1):31-66. 26. Sisson S and Grossman JD. The anatomy of the domestic animals. 4th Edition. London: Charles e. Tuttle 1961:835-75. Cited by Prasada Rao PV, Chaudhary SC. Communication of the musculocutaneous nerve with the median nerve. East Afr Med J 2000;77(9):498-503. 27. Sud M, Sharma A. Absence of musculocutaneous nerve and the innervation of coracobrachialis, biceps brachii and brachialis from the median nerve. J Anat Soc India 2000;49(2):176-7. 28. Sunderland S. The Median Nerve: Anatomical and Physiological features. In: Nerves and Nerve Injury.

29.

30.

31.

32.

2nd edition, Churchill Livingstone: Edinburgh 1978;6727, 691-727. Cited by Chauhan R, Roy TS. Communication between the median and musculocutaneous nerve: a case report. J Anat Soc India 2002;51(1):72-5. Uzun A, Seelig LL Jr. A variation in the formation of the median nerve: communicating branch between the musculocutaneous and median nerves in man. Folia Morphol (Warsz) 2001;60(2):99-101. Venieratos D, Anagnostopoulou S. Classification of communications between the musculocutaneous and median nerves. Clin Anat 1998;11(5):327-31. Watanabe M, Takatsuji K, Sakamoto N, Morit Y, Ito H. Two cases of fusion of the musculocutaneous and median nerves. Kalbo gaki Zasshi 1985; 60:1-7. Cited by A variation of the brachial plexus characterized by the absence of the musculocutaneous nerve: a case report. Surg Radiol Anat 2000;22(1):63-5. Yang ZX, Pho RW, Kour AK, Pereira BP. The musculocutaneous nerve and its branches to the biceps and brachialis muscles. J Hand Surg Am 1995;20(4):671-5.

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The Neurology of Insulin Secretion The autonomic nervous system, which is the part of the nervous system beyond conscious control, plays an important role in the release of insulin from b-cells in the endocrine part of the pancreas. The process by which this occurs has been a mystery, since it is difficult to give detailed study to such an inaccessible organ. However, researchers at Karolinska Institutet in Sweden have now managed to graft b-cells into the eyes of mice in order to study them in a living organism over a prolonged period of time. As a result, the group and a team of colleagues from the University of Miami have gained detailed knowledge of how the autonomic nervous system regulates b-cell insulin secretion. For this study, a technique of transplanting b-cells to the anterior chamber of the mouse eye was used. This technique was previously developed by Professor Per-Olof Berggren’s group at Karolinska Institutet. In the anterior chamber of the eye the b-cells receive a supply not only of blood vessels, but also of nerves from the sympathetic and parasympathetic system, which constitute the autonomic nervous system. Put simply, the sympathetic nervous system can be said to prepare us for flight; one way it does this is to boost our energy by reducing insulin release and increasing glycogen, and consequently blood glucose. The parasympathetic nervous system operates in the reverse direction when we are at rest. _____________________________________________________________________________ A person with Alzheimer’s disease may live anywhere from 2 to 20 years after diagnosis. To lower your Alzheimer’s risk: i) Maintain a healthy weight, ii) check your waist line, iii) eat mindfully (reducing intake of junk food and refined carbohydrates, iv) exercise regularly and v) keep your important health numbers under control such as blood pressure, sugar and cholesterol. As per Harvard News Letter, a recent international survey has shown that Alzheimer’s is the second most feared disease after cancer. It is characterized by progressive damage to nerve cells and their reactions. The result is devastating and includes memory loss, having difficulties with verbal communication and even personality changes.

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obstetrics and gynecology

Fetal Femur Length in Assessment of Gestational Age in Third Trimester in Women of Northern India (Lucknow, UP) and a Comparative Study with Western and Other Asian Countries DP Gupta*, DK Saxena**, Hem Prabha Gupta†, Zaidi Zeeshan‡, RP Gupta#

Abstract Introduction: Gestational age (GA) estimation is the most important part of obstetric practice and ultrasonic study plays an important role in its accurate estimation. Fetal femur length (FL) is one of the parameters used for estimation of GA along with biparietal diameter, head circumference and abdominal circumference (AC). Objective: This study is an attempt to correlate fetal FL with GA and to ascertain if fetal FL can be used as a parameter to calculate the GA in third trimester of pregnancy in Indian women with moderate accuracy. Findings have been compared with the work of sonologists from other countries. Material and methods: Pregnant women in the third trimester of pregnancy with single live fetus and having no other complication either in mother or fetus, were selected for the study, fetal FL along with other parameters was measured. The results were analyzed for accuracy in estimation of GA by FL and were compared with findings of other workers. Result: GA estimated from FL in 512 cases between 27-39 weeks of gestation showed that quadratic model has a good fit to the data and r2 = 0.785 with standard error + 8 days. There was a significant difference with Iranians and Bangladesh women in comparison to our findings. The paired t-test between Indian and Bangladesh, women was significant, (p < 0.001). The findings in our study were similar to the results of Western fetal FLs. Conclusion: The data can be useful in estimation of GA by FL. Our error was + 8 days. A bigger study involving same number of cases in each week of gestation in third trimester is necessary to get an accurate formula for assessment of GA by FL.

Keywords: Gestational age, femur length, estimation

M

ost of the ultrasonic studies have been reported in second trimester using a single parameter biparietal diameter [BPD])1 or multiple parameters head circumference + abdominal circumference (HC +AC) or (HC + FL) or (HC + AC + FL [femur length]). Multiple parameters were found to be slightly superior to HC or BPD alone in the estimation of fetal age. On the basis of the data derived from pregnancies with known conception dates, ultrasound determines the fetal age to within <5 days in first trimester and <7 days in second trimester in

*Associate Professor **Assistant Professor, Dept. of Radiology †Professor, Dept. of Obstetrics and Gynecology ‡Statistician-cum-Lecturer, Dept. of Community Medicine Era’s Lucknow Medical College, Lucknow, Uttar Pradesh #Consultant Pathologist New X-ray and Pathology, Thakurganj, Lucknow, Uttar Pradesh Address for correspondence Dr DP Gupta MIG-2, Napier Road, Part II, LDA Colony, Thakurganj, Lucknow - 226 003 E-mail: dp_gupta2007@yahoo.co.in

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Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

>95% of cases.2 Ultrasonic studies have proven useful in determination of gestational age (GA) in first and second trimester, but their accuracy in third trimester is not reliable because of biologic variations like racial differences in fetal biometric measurements and inter population variations.11 Aims and Objective This study was conducted to evaluate if fetal FL can be used as a parameter in GA determination in third trimester in Indian women and to compare it with the other study in Bangladesh women.3 In Iranian population, it has been reported to be an accurate indicator of GA and has a stronger correlation with GA than BPD.4 The accuracy of fetal FL in the estimation of GA has been mentioned in various studies.5 Material and Methods The study was conducted in 512 pregnant women who came for ultrasonography in the Dept. of Radiology, Era’s Lucknow Medical College and Hospital, Lucknow


obstetrics and gynecology in between October 2011 to October 2012. Only women with >27 weeks CUA (composite ultrasonographic age) till term were included in this study. All patients were examined for any other complication. Gravid females with single live fetus with no complication i.e., congenital anomaly, or growth restriction were included. Women who participated in the study were selected on following criteria:

Table 1. Comparison of Mean GA in Indian, Western and Bangladesh with Regard to Fetal FL FL in MM

Gastational age in weeks Mean (Indian)

2 SD

Mean (Western)

Mean (Bangladesh)

50

27.25

0.42

51

27.54

1.13

27.0

27.6

52

27.68

1.19

27.4

28.1

53

28.51

2.10

27.8

28.5

54

28.10

1.06

28.2

29.0

55

28.75

1.84

28.7

29.5

56

29.14

2.74

29.1

30.0

ÂÂ

Regular menstrual cycles, known date of last menstrual period

ÂÂ

Previous live normal neonates in multipara

ÂÂ

No history of taking tobacco, gutka

ÂÂ

No history of drug abuse

ÂÂ

No history of diabetes, hypertension, tuberculosis

57

29.49

2.30

29.6

30.4

ÂÂ

No uterine anomaly.

58

30.24

2.34

30.0

30.9

All scans were performed by a single ultrasonologist on one ultrasound machine, a Elpro GE logic 200 and a 3.5 MHz sector transducer was used. The long axis of femur was aligned with transducer measuring only the osseous portion of diaphysis and metaphysis of the proximal femur. The entire osseous femur was measured without foreshortening or elongation as described by Filly et al.7,8 Femoral epiphysis is visible after 32 weeks and was not included in measurement. Statistical analysis were conducted by using SPSS version 14.0 software. At each GA, FL indices were reported as mean ± SD (standard deviation). Pearson’s correlation between GA and FL is presented in the form of scatter plot and assessed by Pearson’s product moment correlation coefficient. Its significance was assessed by using t-test.

59

30.60

2.45

30.5

31.4

60

30.63

1.28

30.9

31.9

61

31.13

2.05

31.4

32.4

62

31.58

2.41

31.9

32.9

63

31.16

2.07

32.0

33.5

64

32.52

1.81

33.0

34.0

65

32.66

1.82

33.0

34.5

66

33.47

2.60

33.8

35.6

67

33.09

1.90

34.2

35.9

68

33.94

2.73

34.2

36.1

69

34.08

2.23

34.7

36.7

70

31.18

1.83

35.2

37.2

71

34.61

2.02

35.7

37.8

72

35.47

1.59

36.2

38.4

To predict GA by using FL measurements, linear regression analysis was performed using linear mixed model approach taking GA as dependent variable and FL as independent and also FL as dependent and GA as independent.

73

35.98

2.25

37.2

36.9

74

35.88

3.79

37.4

39.5

75

36.53

1.64

38.3

76

37.43

2.32

38.8

77

36.40

0.00

39.8

Result The study was conducted in 512 women who came for ultrasonography in the third trimester. The maternal age was between 18-38 years with a mean maternal age of 24.79 ± 4. About 37.5% women were from low socioeconomic group and the rest were from middle income group. It was observed that FL increased gradually from a minimum of 50 mm at the 27.25 weeks GA to 76 mm in the 37.43 weeks (Table 1). In 36-38 weeks the increase in FL was slow (Table 2). Data were prepared for FL in different weeks of gestation in form of Tables and Graphs.

Graphs based on quadratic function were prepared. There is high correlation seen between FL and CUA -r2 = 0.785 p < 0.001. Taking CUA as dependent and FL as independent, the coefficient of determination r2 was 0.78625, and the error in estimation of CUA using FL is ± 1.146 weeks or ± 8 days. Taking FL as dependent and CUA as independent the coefficient of determination was r2 = 0.74691. The error in estimation of FL using CUA is ± 3.25. The equation of fitted quadratic curves are:

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

373


obstetrics and gynecology CUA = 0.0074 FL2 – 0.565 FL ± 38.04 FL = 0.046

CUA2

Our study showed accordance with the study of Rashid3 who also reported that Indian fetal FL for a particular GA was more than Bangladesh women, but in our study we found that the Indian fetal FL were similar to the western study (Fig. 3).

+ 5.172 CUA – 55.41

Table 1 shows the mean GA in relation to FL in western, Indian and Bangladesh women. An effort was made to compare the pattern in increase in FL according to GA in the three groups. (Figs. 2 and 3).

Comparing our results with Iranian and Bangladesh study we observed that FL was more in each gestation age as compared to the Iranian and Bangladesh fetus (Fig. 2).

Our results showed that mean FL was similar to the Western measurements and more than Bangladesh measurements for the corresponding GA. In the early weeks of gestation, there was less difference, but as age advanced the difference increased.

Discussion In our study of 512 cases between 27-39 weeks, Table 2 shows the details of number of cases in each

Table 2. Comparison of FL of Indian Women in Percentile No. of cases

Mean FL in mm

27

34

28

GA in weeks

FL in mm percentiles

SD

2 SD

SE

5th

50th

95th

52.03

46.5

51.85

56.4

2.822

5.645

0.484

44

54.11

45.95

54.8

58.3

3.806

7.612

0.574

29

32

57.07

52.825

57.1

62.015

2.477

4.953

0.438

30

36

59.43

55

59.4

62.9

2.378

4.757

0.297

31

60

60.85

55.525

62.3

66.64

4.944

9.889

3.638

32

98

63.80

57.975

63.8

68.02

3.687

7.374

0.372

33

70

65.94

61.165

65.9

70.68

2.716

5.431

0.325

34

53

67.99

62.73

68

71.42

2.418

4.836

0.332

35

32

70.92

66.96

71.3

74.48

2.074

4.149

0.367

36

12

71.96

66

72

77.6

3.322

6.644

0.959

37

10

72.98

66

74

76.3

3.365

6.731

1.064

38

2

70.30

68

70.3

72.6

3.253

6.505

2.300

39

1

76.00

76

76

76

-

-

-

80.0 Present study

70.0

Bangladesh Study

70.00

60.0 55.0 50.0 27

28

29

30

31 32 33 GA in weeks

34

35

36

37

Figure 1. Femur length value at specific weeks of gestation (confidence interval [CI]).

374

Iranian Study

80.00

65.0

Femur length (mm)

95% CI femur length

75.0

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

60.00 50.00 40.00 30.00 20.00 10.00 0.00

27 28 29 30 31 32 33 34 35 36 37 38 39 CUA in weeks

Figure 2. Comparison with Iranian and Bangladesh studies.


obstetrics and gynecology

Femur length (MM)

References 90.00 85.00 80.00 75.00 70.00 65.00 60.00 55.00 50.00 45.00 40.00

Present study

Western Study

1. Campbell S. The prediction of fetal maturity by ultrasonic measurement of the biparietal diameter. J Obstet Gynaecol Br Commonw 1969;76(7):603-9.

Bangladesh Study

2. Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of greatest embryonic length in dated human embryos. Ultrasound Obstet Gynecol 1994;4(6):457-62. 27 28

29 30 31 32 33 34 CUA in weeks

35 36 37 38

39

Figure 3. Comparison with Western and Bangladesh studies.

GA and the mean FL and its percentile in relation to the percentile table. Accordingly the values matched 5th, 50th and 95th percentile table. In the study of Hadlock et al9 they found error of ± 9.5 days between 12-23 weeks and ± 22 days between 23-40 weeks. Yeh et al10 reported a 95% confidence interval of ± 5 days during the period of 22-35 weeks with a maximum variation of ± 6 days, these values are based on analysis of 150 fetuses. While Hadlock et al9 and Hoeler et al12 analyzed over 300 fetuses and they reported the variability during this period to be higher that is ± 3-3.5 weeks. In another study of 900 fetuses by Honarvar4 there is a variability of ± 5 days during 23-40 weeks of gestation. Our study of 512 cases the variability in estimation of GA by using FL is ± 8 days. The results have shown differences with other studies because out of 512 cases, 345 cases were in the 30-34 weeks of gestation and it is during this period increase in FL is maximum. Furthermore, it is during this period of gestation that variations in FL is more between cases in the same week of gestation (Table 2). Kovac et al13 had concluded that Asian groups had a less than – expected FL as compared to Western studies, but in our study FL was similar to the Western studies (Fig. 3). Further studies with equal number of cases in each week of gestation would give a better calculation formula for the estimation of GA by FL. The difference in mean values with other ethinic groups indicates that single formula can not be used for calculation of GA by FL and each population needs different growth charts for accurate calculations.

3. Rashid SQ. Gestational age predicted by femur length in Bangladesh. J Bangladesh Coll Physicians Surg 2010;3: 163-6. 4. Honarvar M, Allahyari M. Assessment of gestational age based on ultrasonic femur length in fetus. Acts Medica Iranica 1999;37(3):134-8. 5. O’Brien GD, Queenan JT, Campbell S. Assessment of gestational age in the second trimester by real-time ultrasound measurement of the femur length. Am J Obstet Gynecol 1981;139(5):540-5. 6. Chervenak FA, Skupski DW, Romero R, Myers MK, Smith-Levitin M, Rosenwaks Z, et al. How accurate is fetal biometry in the assessment of fetal age? Am J Obstet Gynecol 1998;178(4):678-87. 7. Filly RA, Hadlock FP. Sonographic determination of menstrual age. In: Ultrasonography in Obstetrics and Gynecology. Callen PW (Ed.), WB Saunders: Philadelphia 2000:p.146-70. 8. Goldstein RB, Filly RA, Simpson G. Pitfalls in femur length measurements. J Ultrasound Med 1987;6(4):203-7. 9. Hadlock FP, Harrist RB, Deter RL, Park SK. Fetal femur length as a predictor of menstrual age: sonographically measured. AJR Am J Roentgenol 1982;138(5):875-8. 10. Yeh MN, Barron B, Bracero L, Murtha L, Aboulafia M, Reilly K. Ultrasound measurement of femur length as a Index of fetal growth and development. Proceeding of the 26th Annual Meeting if the American Institute of Ultrasound in Medicine. 1981:35. 11. Brooke OG, Butters F, Wood C, Bailey P, Tukmachi F. Size at birth from 37-41 weeks gestation: ethnic standards for British infants of both sexes. J Hum Nutr 1981;35(6):415-30. 12. Hoeler EW, Quetel TA. The relationship between fetal femur length and biparietal diameter in last half of pregnancy. Am J Obstet Gynaecol 1981;141:759-62. 13. Kovac CM, Brown JA, Apodaca CC, Napolitano PG, Pierce B, Patience T, et al. Maternal ethnicity and variation of fetal femur length calculations when screening for Down syndrome. J Ultrasound Med 2002;21(7):719-22; quiz 724-5.

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375


Oncology

Prognostic Impact of CD3 Tumor Infiltrating Lymphocytes in Triple-negative Breast Cancer Ankita Singh Rathore*, Madhu Mati Goel*, Annu Makker*, Sandeep Kumar**, AN Srivastava†

Abstract Background: Aim of the present study was to evaluate the prognostic significance of CD3+ tumor infiltrating lymphocyte (TILs) in triple-negative breast cancer (TNBC). Methods: Immunohistochemistry was done with antibodies to CD3 TIL, estrogen receptors (ERs), progesterone receptor (PR) and C-erbB2 in tissue sections of 49 TNBC patients. CD3+ intratumoral and stromal TILs were counted in relation to known clinicopathological factors. Results: Intratumoral CD3+ TILs were significantly associated with stage (p = 0.05) with insignificant association with age, menopausal status, family history, grade and lymph node status. Higher counts of stromal CD3+ TILs were significantly associated with stage (p = 0.05), whereas grade, lymph node status, age, menopausal status and family history were insignificant with CD3+ count. The higher CD3 intratumoral and stromal counts both showed significant association with good prognosis (p 0.05). Conclusion: CD3+ TILs may serve as good prognostic marker in TNBC. The results of present study need further validation on larger sample size.

Keywords: Tumor infiltrating lymphocytes, triple-negative breast cancer

B

reast cancer is one of the most frequent causes of cancer death in women worldwide1 and is second most common cancer in females in India.2 The predictable prognostic factors in breast cancer include histological grade, clinical stage, lymph node and hormone receptor status. Higher clinical staging and grading are known bad prognostic markers. Lymph node positivity also indicates bad prognosis. However, each kind of tumor has different biological behavior. Triple-negative breast cancer (TNBC) is clearly a distinct subtype of breast cancer.3 TNBC lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and C-erbB2. TNBC are known to be more aggressive with worse prognosis. Tumor infiltrating lymphocytes (TILs) have been thought to play an important role in inhibiting tumor proliferation, metastasis in tumors and may be an

independent prognostic marker.4-7 The infiltrating lymphocytes counts within the tumor cell have been reported to associate with good prognosis in different kind of tumors.8-11 CD3 antigen is a receptor glycoprotein present on all T lymphocytes. Controversy still surrounds the prognostic role of TILs within a tumor microenvironment. While higher concentration of CD3 TIL has been shown to link with favorable outcome in oropharyngeal cancer,12 a low CD3 count has been reported to predict a shorter disease free survival in colon and cervical cancer.13,14 Role of TIL in TNBC is not well-understood. The present study was done to evaluate the density, localization and distribution of CD3 TIL in TNBC patients. The findings were correlated with known clinicopathological factors and survival. Material and Methods

Patients *Dept. of Pathology, King George’s Medical University Lucknow, Uttar Pradesh **All India Institute of Medical Sciences, Bhopal, Madhya Pradesh †Dept. of Pathology, Era’s Lucknow Medical College and Hospital, Lucknow Uttar Pradesh Address for correspondence Dr Ankita Singh Rathore SRF, Dept. of Pathology King George’s Medical University Lucknow - 226 003, Uttar Pradesh E-mail: ankita.rathorekg@gmail.com

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A total of 25 histologically proven cases of TNBC recruited from the Dept. of General Surgery, King George’s Medical University, Lucknow, Uttar Pradesh, India after informed written consent and institutional ethical clearance were included in this study. Demographic details, clinical history, complete general/ local examination and epidemiological risk factors including family history, clinical stage, tumor grade,


Oncology lymph node status, ER, PR and Cerb B2 were recorded on a detailed proforma specially designed for the study. All patients had preoperative tissue diagnosis of breast cancer either by fine-needle aspiration cytology (FNAC) and/or core biopsy of the breast. All the patients underwent surgery with axillary lymph node dissection, and none of these patients had received preoperative antitumor therapy. Detailed histopathological examination was done in the Dept. of Pathology, King George Medical University Lucknow, Uttar Pradesh.

Immunohistochemistry Immunohistochemistry (IHC) was performed using primary antibodies to CD3+ (Novacastra, UK), ER, PR and CerbB-2 (Biogenex Laboratories, Inc, CA, US). Sections were deparaffinized in xylene followed by hydration in graded ethanols. Secondary antibody kit used was polymer detection kit (Novacastra, UK). Formalin-fixed, paraffin-embedded tissues sections (3-4 μm thick) were taken on 3-aminopropyl triethoxysilane (APTS)-coated glass slides. Sections were immersed in antigen-retrieval solution (Citrate buffer pH 6.0) and antigen retrieval was done in the antigen-retrieval system (Biogenex Laboratories, Inc, CA, US) at 100°C for 20 minutes. The sections were then brought to room temperature. Endogenous peroxidase activity was blocked in 3% hydrogen peroxide for 5 minutes and nonspecific binding sites were blocked with protein block for 5 minutes. Sections were covered with 50 μl of individual primary antibody, kept in moist chamber and slides were incubated over night at 40°C. Slides were then washed with tris buffer saline (TBS), followed by a 30 minutes incubation with post-primary block at room temperature (RT). Sections were then washed again in TBS and incubated with secondary antibody for 30 minutes at RT. 3,3-diamino-benzidine was used as chromogen for visuation of antigen antibody complex. Sections were counterstained with hematoxylin and mounted with DPX. Section from tonsillar tissue was taken as positive control for CD3+ cells.

Microscopic Evaluation of CD3 TIL CD3 positive TILs were counted in five randomly selected high power fields at 40X magnification and the counts were averaged. Initially, CD3 positive TILs count was recorded as: + (1-25 cells), ++ (≥25 cells) in the tumor and in the stroma separately. CD3 positive TIL upto 25 cells were considered as low CD3 TIL count and above 25 cells i.e. ++ were considered as high count.

The mean follow-up period was 32 months. Followup data were available for all patients. Details of clinical progress and survival were obtained from the hospital records. During the follow-up period, eight patients were not well (recurrence/death). The histomorphology and immunostaining patterns of intratumoral and stromal CD3 TILs are shown in Figures 1 a and b.

Statistical Analysis Statistical software Stata 11.2 version was used for statistical analysis. The data were described as number and percentages or mean ± SD, as applicable. Chi-square test (χ2) was used to test the association between categorical variables. The age was compared by Mann-Whitney test because of non-normal nature of our data. Results The clinicopathological characteristics of the patients included in this study are summarized in Table 1. The median age of study sample was 50 years (range 25-86 mean 49.16 years). Out of 25 TNBC patients, majority of the cases were postmenopausal (64%). All patients were recruited in the study were TNBC showing higher clinical stage (T3,T4) with 66%, higher histological grade (III, IV) with 52% and lymph node positivity with 60%. The scoring of intratumoral and CD3+ TILs in relation to clinicopathological variables is shown in Table 2. CD3 positive TILs were detected in intratumoral and stromal areas of immunostained histological sections of all the TNBC. Intratumoral CD3+ TILs were significantly associated with clinical stage (p = 0.05). The association of intratumoral CD3 TIL was insignificant in relation to age, menopausal status, family history, histological grade and lymph node status (Table 2). Similarly, the stromal CD3 TIL was also significantly associated with clinical stage (p = 0.05), whereas age, menopausal status, family history, grade and lymph node status did not show significant association with CD3+ stromal TIL count (Table 2). Immunostaining of intratumoral and stromal CD3 TIL are shown in (Figs. 1 a and b). Follow-up for disease-free survival was available for 17 patients. In our analysis, patient with higher intratumoral and stromal CD3+ T-cell infiltration showed a longer disease-free survival (p = 0.004) and (p = 0.01), respectively. Higher number of CD3+ TILs were observed to be associated with better outcome.

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Oncology Stromal CD3 TILs Intratumoral CD3 TILs

(b)

(a)

Figure 1 a and b. Show intratumoral and stromal TILs in TNBC; section showing intratumoral and stromal area of TNBC (H&E x100) (a); immunostain section showing CD3 + in intratumoral and stromal area of TNBC (H&x 100) (b).

Table 1. Clinicopathological Characteristics of the Breast Cancer Patients Characteristics Age (years) Mean Âą SD (range)

n = 25 (100%) 49.16 Âą 12.62 (25-86)

Menopausal status Premenopause

9 (36%)

Postmenopause

16 (64%)

Family history Yes

2 (8%)

No

23 (92%)

Grade I, II

12 (48%)

III, IV

13 (52%)

Tumor stage T1,T2

11 (44%)

T3,T4

14 (66%)

Lymph node status Positive

15 (60%)

Negative

10 (40%)

Survival status Well

17 (68%)

Not well

8 (32%)

Discussion Patients with TNBC have significantly bad prognosis, compared to women with other sybtypes of breast cancer. The fundamental difference between relapse

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and mortality rate of patients may be elucidated in part by different steps of metastatic spread.15 The current assumption is that TNBC metastasize to axillary lymph nodes and bone less frequently than the non TNBC subset of breast cancer, favoring a hematogenous spread.16,17 In the present study, we observed significantly high intratumoral CD3+ counts in relation to tumor stage. Association of CD3+ TILs with other factors like age, menstrual status, family history, histological grade and lymph node status were not significant. High grade, stage and lymph node positivity are known poor prognostic factors in breast cancer. Similar findings have been reported for medullary carcinoma of breast by other workers.18 The presence of CD3+ TILs has been attributed to the positive outcome in several studies.19,20 The high counts of CD3+ TILs compared to low counts have been reported to be associated with better survival in Stage IB cervical cancer.21 In a recent study, the presence of intratumoral CD3+ TILs was associated with better survival in epithelial ovarian cancer.22 It is well-known that women with TNBC had significantly shorter disease free and overall survival time than other subtypes.23 The high intratumoral and stromal TILs in our study predicted longer survival (p = 0.004 and p = 0.01), respectively), implying that higher CD3+ TILs may act as good prognostic marker in TNBC. We used IHC for CD3+ TILs semi-quantification, which had the distinct advantage of morphologically observing the TILs in intratumoral and stromal areas. Further, the size of the histological sections taken for


Oncology Table 2. Association of Intratumoral and Stromal CD3+ Count with Clinicopathological Characteristics Variables

Intratumoral CD3+ count

Stromal CD3+ count

Low (n = 8)

High (n = 17)

p value

Low (n = 9)

High (n = 16)

p value

52.3 ± 11.7

48.5 ± 13.4

0.49

49.8 ± 14.4

49.5 ± 12.2

0.96

(30-80)

(25-86)

(26-87)

(26-85)

Premenopause

4 (50%)

5 (29.41%)

3 (33.33%)

6 (37.5%)

Postmenopause

4 (50%)

12 70.59%)

6 (66.67%)

10 (62.5%)

No

8 (100%)

15 (88.24%)

8 (88.89%)

15 (93.75%)

Yes

0

2 (11.76%)

1 (11.11%)

1 (6.25%)

I-II

2 (25%)

10 (58.82%)

2 (22.22%)

10 (62.5%)

III-IV

6 (75%)

7 (41.18%)

7 (77.78%)

6 (37.5%)

T1-T2

1 (12.5%)

10 (58.82%)

1 (11.11%)

10 (62.5%)

T3-T4

7 (87.5%)

7 (41.18%)

8 (88.89%)

6 (37.5%)

Negative

2 (25%)

8 (47.06%)

3 (33.33%)

7 (43.75%)

Positive

6 (75%)

9 (52.94%)

6 (66.67%)

9 (56.25%)

Well

2 (25%)

15 (88.24%)

3 (33.33%)

14 (87.5%)

Not well

6 (75%)

2 (11.76%)

6 (66.67%)

2 (12.5%)

Age (years) Mean ± SD (range) Menstrual status 0.40

1.00

Family history 1.00

1.00

Grade 0.20

0.09

Stage 0.04

0.03

Lymph node 0.40

0.69

Treatment response

IHC is also significant if morphological observations are to be made separately within the tumor areas and the stromal component. We performed IHCs on larger tissue sections obtained from resected specimens, not on core biopsies. The idea in our study was to locate whether IHC with infiltrating CD3+ TILs could be used as an adjunct to all cases of TNBC. This could be useful in stratifying the patients into high-risk or low-risk category at the time of tissue diagnosis on resected specimen. Conclusion The present study proposes that detection of the density and location of CD3+ TILs in TNBC could be a good prognostic factor. A larger number of sample size need to be studied and linked with their survival. References 1. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol 2001;2(3):133-40.

0.004

0.01

2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127(12):2893-917. 3. Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA. Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat 2009;115(2):423-8. 4. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313(5795):1960-4. 5. Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H, et al. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer 2004;91(9):1711-7. 6. Schumacher K, Haensch W, Röefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res 2001;61(10):3932-6. 7. Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell

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Oncology carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001;61(13):5132-6. 8. Black MM, Speer FD, Opler SR. Structural representations of tumor-host relationships in mammary carcinoma; biologic and prognostic significance. Am J Clin Pathol 1956;26(3):250-65. 9. Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E, et al. Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer 1992;28A(4-5):859-64. 10. Di Giorgio A, Mingazzini P, Sammartino P, Canavese A, Arnone P, Scarpini M. Host defense and survival in patients with lung carcinoma. Cancer 2000;89(10):2038-45.

16. Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, et al. Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and longterm survival. Breast Cancer Res 2007;9(1):R4. 17. Rodríguez-Pinilla SM, Sarrió D, Honrado E, Hardisson D, Calero F, Benitez J, et al. Prognostic significance of basal-like phenotype and fascin expression in nodenegative invasive breast carcinomas. Clin Cancer Res 2006;12(5):1533-9. 18. Guo X, Fan Y, Lang R, Gu F, Chen L, Cui L, et al. Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast. Mod Pathol 2008;21(9):1101-7.

11. Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77(7):1303-10.

19. Rabinowich H, Cohen R, Bruderman I, Steiner Z, Klajman A. Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res 1987;47(1):173-7.

12. Rajjoub S, Basha SR, Einhorn E, Cohen MC, Marvel DM, Sewell DA. Prognostic significance of tumor-infiltrating lymphocytes in oropharyngeal cancer. Ear Nose Throat J 2007;86(8):506-11.

20. Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 1989;142(10):3714-25.

13. Sinicrope FA, Rego RL, Ansell SM, Knutson KL, Foster NR, Sargent DJ. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology 2009;137(4):1270-9.

21. Baxevanis CN, Dedoussis GV, Papadopoulos NG, Missitzis I, Stathopoulos GP, Papamichail M. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. Cancer 1994;74(4):1275-82.

14. Ancuta E, Ancuţa C, Zugun-Eloae F, Iordache C, Chirieac R, Carasevici E. Predictive value of cellular immune response in cervical cancer. Rom J Morphol Embryol 2009;50(4):651-5.

22. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003;348(3):203-13.

15. Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA. Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status. Cancer 2009;115(21):4917-23.

23. Banerjee S, Reis-Filho JS, Ashley S, Steele D, Ashworth A, Lakhani SR, et al. Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol 2006;59(7):729-35.

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It Even Happens in US: Doctor Gave Chemo to Patients without Cancer Hematologist-oncologist Farid Fata, MD, in suburban Detroit, Michigan, was arrested August 6 and charged with Medicare fraud. In a criminal complaint filed in a federal district court in Detroit, prosecutors said that the 48-year-old Dr Fata ordered toxic chemotherapy for patients who did not have cancer or whose cancer was in remission. Rather than keeping their heads down, some employees at Dr. Fata’s high-profile practice challenged his actions before he was arrested, according to the government. One employed oncologist, for example, told agents from the FBI and the Dept. of Health and Human Services that he discovered that Dr Fata had ordered chemotherapy for a patient whose cancer was in remission. This oncologist and other employees also reported that Dr Fata ordered intravenous immunoglobulin (IVIG) for patients whose antibody levels did not warrant the therapy. One nurse practitioner (NP) told federal agents that she pulled the charts for 40 patients scheduled for IVIG therapy and saw that 38 had neither low antibody levels nor a recurrent infection, which is another indication for the treatment. The NP consulted 2 other employees about the issue, and the 3 of them canceled the IVIG therapy for the 38 patients. Dr Fata’s employees had internally challenged other practices they considered unethical, such as fabricating cancer diagnoses in patient records to justify insurance claims for chemotherapy and positron emission tomography (PET) scans. Dr Fata vehemently denies all the allegations.

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Ophthalmology

Effect of Environment on Eyes: A Review Shubhrica

Abstract Environmental factors like pollutants, toxic gases and chemicals, bacteria, smoking, various drugs, variable humidity, temperature variations, ultraviolet radiations, cosmetics affect the various parts of eyes like cornea, conjunctiva, etc. in several ways and leads to plenty of eye disorders like cataract, conjunctivitis, glaucoma and dry eye.

Keywords: Pollutants, smoking, ultraviolet radiations, cataract, conjunctivitis, glaucoma, dry eye

S

everal eye disorders are seen in smokers and those who are frequently exposed to tobacco smoke. Passive smoking has negative effects on eyes of children. The eye diseases and conditions associated with exposure to tobacco smoke in children include strabismus. Maternal smoking during pregnancy is associated with 6.55 times increased risk of strabismus amongst children of such mothers. Risk of allergic conjunctivitis is increased by about 20% in children who are exposed to environmental tobacco smoke. Smoking cigarettes in adults is associated with cataract more so for nuclear cataract i.e., three times and subcapsular posterior cataract. Endotoxins formed in tobacco smoke induce inflammatory response and acute uveitis. Smoking also causes age-related macular degeneration.1-3 Environmental tobacco smoke exposure increases risk of ophthalmopathy in Graveâ&#x20AC;&#x2122;s disease. Smokers with thyroid eye disease have poor prognosis as compared to nonsmokers. A direct correlation exists between thyroid eye disease and amount of smoking.4 Smoking affects the ocular surface, which results in symptoms like itchiness, redness and irritation of eyes. The changes on ocular surface associated with smoking include alteration in lipid layer of tear film, reduced tear secretion and decreased corneal and conjunctival sensitivity. Passive smoking

Dept. of Ophthalmology Pt. BD Sharma, PGIMS, Rohtak, Haryana Address for correspondence Dr Shubhrica Dept. of Ophthalmology Pt. BD Sharma PGIMS 30/9J, Medical Enclave, Rohtak, Haryana

can also increase the risk of these disorders. Ocular surface disorders include atopic keratoconjunctivitis and allergic conjunctivitis.1 Cigarette smoking causes primary open angle glaucoma.5 Allergic conjunctivitis is the most common disease seen with environmental variations. It includes acute, chronic, vernal conjunctivitis and others are allergic dermatoconjunctivitis, microbiallergic conjunctivitis, giant papillary conjunctivitis. Acute allergic conjunctivitis is seasonal or perennial and associated with type 1 immediate hypersensitivity reaction-mediated by immunoglobulin E (IgE) and mast cell activation stimulated by direct exposure of ocular mucosal surfaces to environmental allergens like dust grass, molds, pollens, spores and animal dander.6 Reaction may be limited to eyes or may be part of generalized allergic reaction with nasal and respiratory symptoms. A family history of atopy may be present. Conjunctival scrappings show eosinophilic infilteration and elevated levels of IgE and histamine in tear film.7 Acute allergic conjunctivitis is frequently seasonal and sometimes perennial.8 The onset of seasonal allergic conjunctivitis is related to circulating aeroantigens. While perennial is a variant of seasonal allergic conjunctivitis, which persists throughout the year but seasonal exacerbations may be observed. It is usually bilateral and itâ&#x20AC;&#x2122;s clinical features include itching, burning and mild-to-moderate infection, which may progress to variable degree of glassy chemosis with papillary reaction more so in the upper tarsal conjunctiva. A watery or mucoid stringy discharge may be present.9 Chronic atopic keratoconjunctivitis is chronic inflammatory disease usually associated with eczema or asthma.6 It is common in late teens but may be seen upto the fifth decade and has slight male preponderance.

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Ophthalmology Conjunctiva as well as cornea may be involved. The clinical features involve bilateral itching, tearing, burning, photophobia, blurred vision and stringy mucus discharge. Papillary hypertrophy of upper as well as lower tarsal conjunctiva may occur. In severe cases, gelatinous limbal hyperplasia or nodules with or without Horner Trantas dots, cicatrizing conjunctivitis with subepithelial fibrosis, symblepharon formation and forniceal shortening may occur.7 A variable number of mast cells, eosinophil and lymphocytes are found in conjunctival epithelium. T-cell is primary effector cell in atopic keratoconjunctivitis as well as vernal keratoconjunctivitis.7,8 Vernal conjunctivitis is recurrent inflammation of conjunctiva of children and young adults. This is usually bilateral and may be associated with asthma or eczema, more so in spring and summer season and inflammation goes into remission during winter.10 It’s highest incidence is in warm, temperate MiddleEast Mediterranean region and Mexico. It is two times more common in males as compared to females with peak incidence between ages of 11 and 13 years. The disease is self-limiting with average duration of 4-10 years. In adults, the more severe form of disease may recur indefinitely. Symptoms include intense pruritis, photophobia, burning, tearing, mild ptosis and thick, stringy, yellow, mucoid discharge. There are three forms of vernal conjunctivitis i.e., palpebral, limbal and mixed.11 In palpebral form, cobblestone papillae are present on superior tarsal conjunctiva, whereas lower lid is minimally affected. First of all papillary hypertrophy occurs, then connective tissue of substantia propria undergoes hyperplasia and proliferate to form giant papillae, which can reach upto 7-8 mm in diameter. In limbal form broad, thickened, gelatinous opacification of superior limbus, which overrides cornea occurs. Horner-Trantas dots, which are white chalk like dots composed of eosinophils and epithelial debris located at limbus are present in limbal form of vernal conjunctivitis. Histologically, the tissue get infilterated with lymphocytes, plasma cells, macrophages, basophils and many eosinophils. Cornea is involved in 50% cases. Corneal changes include superficial pannus and punctate epithelial keratitis. Small, gray patches of necrotizing epithelium may involve upper one-third to two-thirds of cornea and in severe cases, cornea appears to be dusted with flour.11 A vernal ‘shield ulcer’ develops as a horizontally oval, shallow nonvascularized, indolent ulcer of superior cornea, which leads to discomfort. When the ulcer heals, a mild corneal opacity may

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persist at Bowman’s layer. Allergic conjunctivitis is treated by cold compresses, preservative free refrigerated artificial tears and avoidance of allergens. In moderate cases, decongestants, antihistamines, mast stabilizing and anti-inflammatory agents are used. In severe cases, which can’t be treated by above treatment, a short course of topical steroids is given in addition to antihistamines and mast cell stabilizers in order to acutely control the inflammation.8,12 Allergic dermatoconjunctivitis represents delayed cell-mediated (type IV) hypersensitivity reaction and occurs due to reaction by eye drops, cosmetics, clothing, jewelry, plastics, animal or vegetable products and industrial chemicals.13 Previous sensitization would have occurred as little as five days or as long as years previously. The eye drugs commonly associated with this reaction include neomycin, gentamicin, idoxuridine, atropine, thimerosal and penicillin.14 Preservatives may stimulate allergy. Allergic reaction starts with severe itching and papillary conjunctivitis, which is worse on inferior palpebral conjunctiva. Mucoid or mucopurulent discharge is present and adjacent skin of lower lids and lateral canthi is involved in eczematous dermatitis. Chronic use of allergen causes lid keratinization with punctal edema and stenosis. Cornea may show punctate epithelial keratitis and erosions. Conjunctival scrappings show monocytes, polymorphonuclear neutrophils, leukocytes, mucus and eosinophils. Treatment includes elimination of antigenic stimulus and quieting the eye with antihistamines, mast-cell stabilizers and topical corticosteroids. Microbiallergic conjunctivitis is type IV hypersensitivity response to toxic protein breakdown products of bacterial disintegration and frequently seen with chronic staphylococcal blepharoconjunctivitis, Candida albicans, Coccidioides immitis, Chlamydia, parasites and lymphogranuloma venereum.15 Phlyctenular disease presents as slightly raised, small, pinkish white or yellow nodules surrounded by dilated vessels present on cornea near the limbus or on peripheral cornea. Later on, superficial part of raised nodule becomes gray and soft, center of lesion ulcerates, sloughs and clears without scarring. There is no clear zone between limbus and lesion. This is bilateral and there is a seasonal involvement, more so in spring and summer season. This is most frequently seen in children and young adults. Treatment includes identification of inciting organism and it’s eradication. Twice-daily lid scrubs should be done. Topical antibiotic or antibiotic-corticosteroid combination ointment or drops should be rubbed into


Ophthalmology the lid margins, which reduces the number of bacterial colonies. Systemic antibiotics like oral tetracycline 250 mg four times a day or oral doxycycline 100 mg twice a day helps in treating nontuberculous phlyctenular disease or persistent staphylococcal blepharoconjunctivitis. Giant papillary conjunctivitis is syndrome of inflammation of upper palpebral conjunctiva associated with contact lens wear, ocular prostheses, and protruding ocular sutures. It is found 10 times more frequently in soft lens wearers than in rigid lens wearers.16 Symptoms develop in eight months and eight years in soft and hard lens wearers, respectively. Prevalence is 1-5% in soft lens users and 1% in rigid lens users. Symptoms include mild itching after contact lens removal and increased mucus on lenses and in nasal canthus upon awaking. Patient also complaints of increased lens awareness, blurring of vision after hours of lens wear, excessive lens movement and contact lens intolerance. Treatment includes removal of inciting factors. Environmental illumination influences human health and well-being. Photoreceptive retinal ganglion cells (pRGCs) are primary mediators of numerous circadian, neuroendocrine and neurobehavioral responses. pRGCs provide lighting information to diverse nonvisual (nonimage forming) brain centers including suprachiasmatic nuclei, which serve as bodyâ&#x20AC;&#x2122;s master biological clock. The timing and strength (amplitude) of suprachiasmatic nucleus (SCN) rhythmic signals are affected by light exposure. The critical role of light is most important geophysical timing cue in humans. Typical residential lighting is insufficient for optimal pRGC requirements in youth and even more so with advancing age. Diverse morbidities associated with chronodisruption are caused by light deficiency.17 Increased frequency of lens opacities due to indoor fuel exposure, in particular biofuel and negative effects of styrene exposure on color vision has been reported. Carbon disulfide leads to increased retinal venous diameters. Carbon monoxide exposure causes increase in arterial and venous diameters, retinal blood flow velocity and fundus pulsation amplitude. The relation of light exposure on retinal damage has been observed.18 The level of humidity affects the eyes. In dry and windy weather, eye symptoms will worsen; whereas increased environmental humidity is soothing for the dry eyes. In highly air conditioned places such as department stores, malls and aircrafts with low humidity, may

exacerbate the symptoms where lubricating eye drops are helpful. Ultraviolet radiation either from sun or artificial source may affect the eye. It may affect skin, conjunctiva, cornea as well as the lens leading to cataract and rarely lid cancer. Prolonged short-term exposure can cause changes in the eyes akin to sunburn of the skin. Other eye changes may be pterygium and snow blindness (photokeratitis), which may be prevented by wearing sunglasses. Skin cancer is basal cell carcinoma of lower lid but can occur anywhere on the eyelids including the eyebrows and skin around the eyes.19 Dry eye syndrome is due to decrease in quality or quantity of tears. It may result in decreased sensitivity of cornea. It may be due to excessive evaporation or decreased formation of tears and decreased sensitivity of cornea. It may be exacerbated by dry environment and can be treated by artificial tears.20-22 Blinking replenishes the thin layer of tears covering our eyes. This film evaporates at quick pace in old age. Air becomes dry in heated or air conditioned places, which causes eye irritation. Mild dry eye symptoms may be observed due to decreased blinking as in prolonged computer use. This may also be seen in conditions that increase evaporation of tears as in dry, windy weather. Some patients may notice discomfort only when they wear their contact lenses. Amount of tear is decreased in certain conditions like aging, medications especially antihistamines, menopause, chemical burns, smoking, passive smoking, an eye or eyelid injury, drooping of eyelids, exophthalmos, eyelid paralysis or deformity, Sjogrenâ&#x20AC;&#x2122;s syndrome and rheumatoid arthritis.23 Symptoms of dry eyes include eye fatigue and discomfort, redness, itching, dryness, irritation, discharge or crusting of lids, blurry vision, pain, burning, foreign body sensation, difficulty in wearing contact lenses. Dry eye symptoms in computer users is known as computer vision syndrome. Dry eye may also be observed after Lasik surgery. Dry eye leads to stasis of environment pollutants in eye like pollen, smoke and dust. During reading and TV or computer viewing the rate of eyelids blinking reduces significantly. Use of artificial tears, avoidance of smoking, use of humidifier and purposeful blinking obviate dry eye. REFERENCES 1. Lois N, Abdelkader E, Reglitz K, Garden C, Ayres JG. Environmental tobacco smoke exposure and eye disease. Br J Ophthalmol 2008;92(10):1304-10.

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Ophthalmology 2. Kelly SP, Thornton J, Edwards R, Sahu A, Harrison R. Smoking and cataract: review of causal association. J Cataract Refract Surg 2005;31(12):2395-404. 3. Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP. Smoking and age-related macular degeneration: a review of association. Eye (Lond) 2005;19(9):935-44. 4. Thornton J, Kelly SP, Harrison RA, Edwards R. Cigarette smoking and thyroid eye disease: a systematic review. Eye (Lond) 2007;21(9):1135-45. 5. Edwards R, Thornton J, Ajit R, Harrison RA, Kelly SP. Cigarette smoking and primary open angle glaucoma: a systematic review. J Glaucoma 2008;17(7):558-66. 6. Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 2005;115(1):118-22. 7. Bielory L. Allergic and immunologic disorders of the eye. Part II: ocular allergy. J Allergy Clin Immunol 2000;106(6):1019-32. 8. Stahl JL, Barney NP. Ocular allergic disease. Curr Opin Allergy Clin Immunol 2004;4(5):455-9.

Sugar J, Edelhauser HF (Eds.), Mosby: London 1994: p.2.8-9. 14. Wilson FM 2nd. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmol 1979;24(2):57-88. 15. Woods AC. The diagnosis and treatment of ocular allergy. Am J Ophthalmol 1949;32(11):1457-78. 16. Binder PS. The physiologic effects of extended wear soft contact lenses. Ophthalmology 1980;87(8):745-9. 17. Turner PL, Van Someren EJ, Mainster MA. The role of environmental light in sleep and health: effects of ocular aging and cataract surgery. Sleep Med Rev 2010;14(4): 269-80. 18. Rozanova E, Heilig P, Godnić-Cvar J. The eye - a neglected organ in environmental and occupational medicine: an overview of known environmental and occupational non-traumatic effects on the eyes. Arh Hig Rada Toksikol 2009;60(2):205-15. 19. Van Kuijk FJ. Effects of ultraviolet light on the eye: role of protective glasses. Environ Health Perspect 1991;96:177-84.

9. Tuft SJ, Kemeny DM, Dart JK, Buckley RJ. Clinical features of atopic keratoconjunctivitis. Ophthalmology 1991;98(2):150-8.

20. Tu EY, Rheinstrom S. Dry eye. In: Ophthalmology. 3rd edition, Yanoff M, Duker JS, (Eds.), Mosby Elsevier: St. Louis, MO 2008:p.324-9.

10. Beigelman MN. Vernal conjunctivitis. Los Angeles. University of Southern California Press, 1950.

21. Yanoff M, Cameron D. Diseases of the visual system. In: Cecil Medicine. 24th edition, Goldman L, Ausiello D (Eds.), Saunders Elsevier: Philadelphia, Pa; 2011.

11. Stock EL Meisler DM. Vernal conjunctivitis. In: Duane’s Clinical Ophthalmology. Vol. 4. Tasman W, Jaeger EA (Eds.), JB Lippincott: Philadelphia 1995:p.9.1-5. 12. Foster CS, Duncan J. Randomized clinical trial of topically administered cromolyn sodium for vernal keratoconjunctivitis. Am J Ophthalmol 1980;90(2):175-81. 13. Rheinstrom SD. The conjunctiva. In: Textbook of Ophthalmology. Vol. 8: External Diseases. Chandler JW,

22. Nguyen T, Latkany R. Review of hydroxypropyl cellulose ophthalmic inserts for treatment of dry eye. Clin Ophthalmol 2011;5:587-91. 23. Carsons S. Sjögren’s syndrome. In: Kelley’s Textbook of Rheumatology. 8th edition, Firestein GS, Budd RC, Harris ED Jr, et al. (Eds.), Saunders Elsevier: Philadelphia, Pa 2008:p.1149-68.

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Ching-Chun Lin, MA, from the Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taiwan, and colleagues have reported in the August issue of Ophthalmology that patients with sleep apnea were 1.67 times more likely to develop glaucoma than patients without apnea. The study compared more than 1,000 apnea patients aged 40 years and older with more than 6,000 age-matched participants. (Source: Medscape)

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Pharmacology

Torsemide: A New Loop Diuretic M. Vadivelan*, AS Dabhi*

Abstract Loop diuretics are often administered to hospitalized patients to augment urinary output. They play an essential role in the treatment of fluid overload in patients of congestive heart failure and chronic renal failure. Torsemide is a new loop diuretic that has revolutionized the therapy of fluid overload disorders. Torsemide has a higher bioavailability, greater potency and longer duration of action than frusemide. Torsemide causes significantly greater diuresis, natriuresis, lesser kaluresis, greater reduction in body weight and improvement in edema and ascites as compared to frusemide.

Keywords: Loop diuretics, diuretic resistance

A

loop diuretic inhibits the activity of the Na+/ K+/2Cl– symporter in the thick limb of loop of Henle. Loop diuretics are sometimes called high –ceiling diuretics due to their high efficacy.

It also inhibits Ca+2 and Mg+2 reabsorption in the ascending limb of loop of Henle by abolishing the transepithelial potential difference that is the dominant driving force for the reabsorption of these cations.2

Torsemide is a new agent in this class. Torsemide is an oral as well as intravenous (IV) loop diuretic, the most active of a new series of anilinopyridine sulfonylurea derivatives. Torsemide received approval for clinical use by the US Food and Drug Administration (FDA) on August 23, 1993.

Thus, torsemide has a significant hemodynamic effect in patients with essential hypertension and chronic renal failure - in both the conditions; it lowers the systolic and diastolic blood pressure. It reduces both preload and after load in patients with heart failure.

CLINICAL PHARMACOLOGY

Owing to blockade of the Na+/K+/2Cl– symporter, torsemide increases the urinary excretion of Na+ and Cl– profoundly. Initially, it increases the excretion of uric acid whereas chronic administration results in reduced uric acid excretion. The chronic effects on uric acid excretion may be due to enhanced transport in the proximal tubules secondary to volume depletion, leading to increased uric acid reabsorption or to competition between torsemide and uric acid for the organic acid secretory mechanism in the proximal tubule, leading to reduced uric acid excretion.

Mechanism of Action The actions of torsemide can be mediated by several mechanisms operating within the thick, medullary segment of ascending loop of Henle. These include a) interference with Na+/K+/2Cl– co-transporter at the luminal surface; b) Na–K pump and c) anion exchange.1 Torsemide selectively blocks the active sodium and chloride reabsorption in the thick ascending loop of Henle promoting rapid excretion of water, sodium and chloride. This action is a result of binding of the diuretic to a chloride ion-binding site of the transport molecule.

*Assistant Professor, Dept. of Medicine Medical College and SSG Hospital, Vadodara, Gujarat Address for correspondence Dr M Vadivelan B-290, Saurabh Park Behind Samta Flats, Subhanpura, Vadodara, Gujarat - 390 023 E-mail: mevadivelan @hotmail.com

Effects on Urinary Excretion

Effects on Renal Hemodynamics Torsemide does not have a significant effect on the glomerular filtration rate (GFR). Torsemide is known to induce a rise in serum level of renin and this response is thought to be mediated by renal prostaglandins. Fifty percent of the diuretic effect of torsemide may be secondary to increased production of renal prostaglandins resulting in renal vasodilatation.

Other Actions Before the onset of diuresis, torsemide acutely decreases systemic venous capacitance and thereby

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Pharmacology Table 1. Comparison of Pharmacokinetics of Torsemide - IV Versus Oral Torsemide IV Bioavailability

100%

91%

10 minutes

<60 minutes

Tmax

30 minutes

90 minutes

3 hours

3 hours 30 minutes

27%

21%

Excretion Kidney Liver Diuresis effect

Torsemide IV has 100% bioavailability and oral has 91% bioavailability compared to just 40% with oral frusemide which indicates that switching over from torsemide IV to oral with the same dose is possible due to the high bioavailability of both IV and oral torsemide. Thus, with any active dose, the diuresis is as large after oral as after IV administration of torsemide.

ÂÂ

Torsemide has three times longer half-life than frusemide (3 hours vs. 0.8 hours). Independent of the rate of administration of torsemide, diuresis lasts about 6-8 hours and is 3 times longer than frusemide.

ÂÂ

Torsemide is mainly eliminated hepatically (73%), while frusemide is excreted renally (83%). This prevents the accumulation of torsemide in patients with renal insufficiency. Volume of distribution, plasma clearance and half-life are not altered despite the fall in renal clearance due to renal failure with the use of torsemide. These characteristics make torsemide a good choice for the treatment of patients with renal failure.

ÂÂ

Torsemide causes less loss of potassium in comparison to frusemide. This may be accounted by the fact that torsemide in contrast to frusemide is devoid of a proximal tubular site of action.3

ÂÂ

Torsemide is twice as potent compared to frusemide by IV route.3

ÂÂ

Torsemide demonstrates longer natriuretic activity than frusemide.3

Torsemide oral

Onset of action Half life

ÂÂ

73%

79%

6-8 hours

6-8 hours

reduces left ventricular filling pressure. This effect that may be mediated by prostaglandins and requires intact kidneys, hence benefits patients with pulmonary edema. Torsemide also appears to have an antialdosterone effect that can achieve more efficient diuresis in patients with liver disease. PHARMACOKINETICS Plasma protein binding of torsemide is 97-99%. The duration of diuresis is independent of the route of administration and lasts for 6-8 hours. The volume of distribution of torsemide is 12-15 liters in normal adults or in patients with mild-to-moderate renal failure or congestive heart failure. In patients with cirrhosis, the volume of distribution is approximately doubled. Metabolism and elimination: Torsemide is metabolized by the hepatic cytochrome P450 enzyme system. About 73% is excreted through liver metabolism, and 27% is excreted in urine (Table 1). Renal failure reduces torsemide renal clearance, but plasma elimination half-life is unchanged. A diuretic response in renal failure may still be achieved if patients are given higher doses. The total plasma clearance and elimination half-life of IV torsemide remains normal under impaired renal function because metabolic elimination by liver remains intact. In patients with hepatic cirrhosis, the volume of distribution, plasma half-life and renal clearance are all increased, but total clearance is unchanged. The pharmacokinetic profile of torsemide in healthy elderly subjects is similar to that in young subjects total plasma clearance and elimination half-life remain unchanged. Pharmacological frusemide:3

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superiority

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APPROVED INDICATIONS1 Torsemide can be used for the treatment of: ÂÂ

Acute pulmonary edema: Torsemide increases median fractional sodium excretion significantly along with hourly urine output. This results in significant improvement in both pulmonary rales and orthopnea.4

ÂÂ

Congestive heart failure (CHF): Torsemide is well-tolerated in the treatment of sodium and fluid retention resulting from moderate-to-severe CHF. Torsemide reduces pulmonary congestion, peripheral edema, ascites, jugular venous pressure and body weight. Thus, it improves cardiac function and exercise tolerance.

ÂÂ

Chronic renal failure (CRF): Torsemide increases fractional excretion of urinary volume, sodium and chloride. It is found to be efficacious even in patients with hemodialysis.5


Pharmacology Torsemide also leads to a marked decrease in body weight due to reduction in edema. Similarly, reduction in blood pressure is also seen with torsemide. The cumulative natriuresis response is essentially the same after IV and oral administration of torsemide that is consistent with the complete bioavailability of torsemide (IV and oral) in CRF patients.5

CONTRAINDICATIONS1 Torsemide is contraindicated in ÂÂ

Patients with known hypersensitivity to torsemide or to sulfonylureas.

ÂÂ

Anuric patients.

ÂÂ

ÂÂ

Acute renal failure (ARF): Torsemide has been shown to convert oliguric phase to non-oliguric phase in ARF patients.

Patients with electrolyte imbalance e.g. Hypokalemia, hyponatremia, hypochloremia or hypomagnesemia. Monitoring of serum electrolytes is recommended during torsemide therapy.

ÂÂ

Cirrhotic ascites: Torsemide induces higher urinary excretion of sodium and urine flow rate at 1 hour than frusemide.6

Patients with ventricular arrhythmias should be monitored closely since torsemide-induced hypokalemia can exacerbate these conditions.

ÂÂ

Hypertension: Torsemide causes reduction in both systolic and diastolic blood pressures (20 and 8 mmHg, respectively). This reduction is seen 2 hours after the initial dose.4

WARNINGS ÂÂ

Ototoxicity: Tinnitus and reversible hearing loss have been observed after rapid IV injection especially in high doses. But, it is much less common as compared to frusemide.

ÂÂ

Excessive diuresis with torsemide may cause dehydration, hypovolemia and electrolyte imbalance.

ÂÂ

The risk of hypokalemia is greatest in patients with cirrhosis of the liver, those experiencing a brisk diuresis, those with inadequate oral intake of electrolytes and patients receiving corticosteroids.

DOSAGE AND ADMINISTRATION Because of the higher bioavailability of torsemide, oral and IV doses are equivalent. Thus patients may be switched to and from the IV form with no change in dose. Torsemide IV should be administered either slowly as a bolus over a period of two minutes or administered as a continuous infusion. Initial starting dose is 10-20 mg o.d. Single maximum dose should not exceed 200 mg. No dosage adjustment is needed in patients with hepatic or renal impairment. High doses of torsemide may be effective in patients with end-stage renal disease. No dosage adjustment is needed in patients undergoing intermittent hemodialysis as torsemide is not removed by hemodialysis.

Over Dosage There is no human experience with overdosage of torsemide, but the signs and symptoms of overdosage can be anticipated to those of excessive pharmacological effects resulting in dehydration, hypovolemia, hypotension, hypokalemia, hyponatremia, hypochloremic alkalosis and hemoconcentration. Treatment of overdosage should include IV fluids and electrolyte replacement. Laboratory determination of serum levels of torsemide and its metabolites are not widely available. No data are available to suggest physiological maneuvers that might accelerate elimination of torsemide and its metabolites. Torsemide is not dialyzable, so hemodialysis will not accelerate elimination.

ADVERSE EVENTS1 The following adverse drug reactions have been noted with the use of torsemide – ÂÂ

Dizziness and headache

ÂÂ

Insomnia and nausea

ÂÂ

Orthostatic hypotension

ÂÂ

Arrhythmias e.g., atrial fibrillation, ventricular tachycardia.

ÂÂ

Hypokalemia

ÂÂ

Hyperuricemia

ÂÂ

Pain

DRUG-DRUG INTERACTIONS1 Torsemide when used along with some drugs can lead to specific interactions as follows: ÂÂ

Spironolactone: Torsemide decreases the renal clearance of spironolactone.

ÂÂ

Salicylates - In high doses, torsemide can lead to salicylate toxicity.

ÂÂ

Indomethacin: Natriuretic effect of torsemide is partially inhibited under dietary sodium restriction.

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Pharmacology ÂÂ

Probenecid: Decreases the diuretic activity of torsemide.

Advantages of torsemide continuous infusion (CI): ÂÂ

persistently maintains effective amounts of torsemide at the active site; thus making it a more efficient dosing regimen.

ÂÂ

CI produces a more consistent urine flow.

ÂÂ

CI has less chances of causing alterations in fluid balance and electrolytes.

ÂÂ

CI has less toxicity due to the avoidance of high peak serum concentrations.

ÂÂ

CI overcomes diuretic resistance: Diuretic resistance also known as diuretic tolerance, occurs when the kidneys adapt to chronic high dose diuretic therapy by stimulating sodium retention.7 This is more commonly seen in moderate and severe CHF.

ÂÂ

CI overcomes diuretic braking- Diuretic braking is a process by which the body slowly adapts to and resists the diuretic effect of diuretics by increasing the activity of the sympathetic nervous system, renin-angiotensin-aldosterone system and the release of antidiuretic hormone.

SUMMARY Torsemide is a potent loop diuretic with a rapid onset of action, long half-life and duration of action. It has high bioavailability and is twice more potent than frusemide. Unlike frusemide, the half-life and duration of action of torsemide are not dependent on renal function and so, it does not accumulate in renal failure. No dosage adjustment is required in elderly patients when torsemide is used. Torsemide improves pulmonary rales and orthopnea in patients with acute pulmonary edema.

Similarly, in CHF, torsemide causes significant diuresis and natriuresis and decreases body weight. In ARF, torsemide converts oliguric phase to nonoliguric phase. Torsemide causes greater sodium excretion and decrease in body weight as compared to frusemide in CHF. Torsemide CI has greater efficacy than single dosage that helps in overcoming diuretic resistance and diuretic braking phenomenon. REFERENCES 1. Kruck F, Mutschler E, Knauf H. Mechanism of action of torsemide, indications, contraindications, adverse events and drug interactions. Physician’s desk reference 2004;58th edition:p.2900-2. 2. Edwin K. Jackson-Mechanism of action of loop diuretics. Goodman and Gilman - The Pharmacological Basis of Therapeutics.11th edition. Mc-Graw Hill: USA 2006:p.749-52. 3. Lesne M. Comparison of the pharmacokinetics and pharmacodynamics of torasemide and furosemide in healthy volunteers. Arzneimittelforschung 1988;38(1A):160-3. 4. Stringer KA, Watson W, Gratton M, Wolfe R. Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema. J Clin Pharmacol 1994;34(11):1083-7. 5. Boesken WH, Kult J. High-dose torasemide, given once daily intravenously for one week, in patients with advanced chronic renal failure. Clin Nephrol 1997;48(1):22-8. 6. Gentilini P, La Villa G, Marra F, Carloni V, Melani L, Foschi M, et al. Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites. J Hepatol 1996;25(4):481-90. 7. Paul S. Balancing diuretic therapy in heart failure: loop diuretics, thiazides, and aldosterone antagonists. Congest Heart Fail 2002;8(6):307-12.

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A mobile-bearing, bone-sparing cervical spinal disc device for single-level replacement has been approved by the FDA. The Mobi-C Cervical Disc device, the first such replacement disc to win FDA approval is an attractive treatment alternative to anterior cervical discectomy fusion according to the manufacturer. The approval was based on a trial comparing the discectomy procedure with disk replacement using the Mobi–C device. After two years, LDR said, outcomes showed that the device was not inferior to the discectomy surgery. Overall treatment success rates were slightly higher with the device (73.7% vs 65.3%) and secondary surgeries at the index level for the device were less frequent (1.2% vs 6.2%). (Source: Medpage Today)

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mediLAW

When can Hospitals be Liable for Medical Negligence Deaths?

I

f a patient dies due to medical negligence in a hospital then its management cannot be prosecuted and it is only the doctors who should be penalized, the Delhi High Court has ruled. However, the Court held that the management of the hospital would be liable in case of administrative negligence and failure to provide basic infrastructure to patients.

complaint case under Section 336/337/471 read with Section 34 IPC qua the petitioner. It is submitted that petitioner Indraprastha Medical Corporation Limited was a company incorporated under Companies Act and the company being only a juristic person was incapable of committing a crime of medical negligence, because it involved personal negligent act.

Justice SN Dhingra passed the order on a petition filed by Indraprastha Medical Corporation Limited challenging a metropolitan magistrate’s order for registration of a first information report against it for alleged medical negligence resulting in the death of a patient in 2007.

A complaint was filed before the learned M.M. against the petitioner company and the Doctors involved in the treatment of deceased wherein it was alleged that deceased died due to gross medical negligence of the Doctors. It is also submitted that Doctors involved in treatment advised wrong/superfluous treatments in order to extract extra money. The petitioner’s counsel stated that petitioner is not assailing the order as against Doctors but is assailing it so far as company was concerned on the ground that the company running the hospital, could not have acted in the manner in which it is assailed by the complainant.

Setting aside the trial court order, Justice Dhingra said: “The hospital or company cannot be held liable for the personal negligence of the doctor in giving wrong treatment.” “If there is an administrative negligence or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable”. The Court, said that it is the doctor who treats the patients and hospitals should not be punished due to error on part of its medical staff. “The offence of medical criminal negligence cannot be fastened on the company since the company can neither treat nor operate a patient of its own.” “It is the doctor working in the hospital who treats and performs operations. It is the doctors who examines the patients and prescribe medicines. If there is a deliberate or negligent act of the doctor working in the hospital, it is the liability of the doctor and not of the hospitals for criminal negligence,” the court said. In the present case, the company contended that the hospital could not be held responsible as the patient was being treated by three doctors from the Dept. of Cardiology a few years back. Judgment: Present petition has been filed by the petitioner for quashing of order dated 19th December, 2007, passed by learned Metropolitan Magistrate in a

In Standard Chartered Bank Vs. Directorate of Enforcement, 2005 SCC (Cri.) 961, SC made following observations regarding criminal liability of the Corporation: “6. There is no dispute that a company is liable to be prosecuted and punished for criminal offences. Although there are earlier authorities to the effect that corporations cannot commit a crime, the generally accepted modern rule is that except for such crimes as a corporation is held incapable of committing by reason of the fact that they involve personal malicious intent, a corporation may be subject to indictment or other criminal process, although the criminal act is committed through its agents. 8. Inasmuch as all criminal and quasi-criminal offences are creatures of statute, the amenability of the corporation to prosecution necessarily depends upon the terminology employed in the statute. In the case of strict liability, the terminology employed by the legislature is such as to reveal an intent that guilt shall not be predicated upon the automatic breach of the statute but on the establishment of the actus reus, subject to the defence of due diligence. The law is primarily based on the terms of the statutes. In the case of absolute liability where the legislature by the clearest

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mediLAW intendment establishes an offence where liability arises instantly upon the breach of the statutory prohibition, no particular state of mind is a prerequisite to guilt. Corporations and individual persons stand on the same footing in the face of such a statutory offence. It is a case of automatic primary responsibility. It is only in a case requiring mens rea, a question arises whether a corporation could be attributed with requisite mens rea to prove the guilt. But as we are not concerned with this question in these proceedings, we do not express any opinion on that issue.” In Kalpnath Rai Vs. State, 1998 AIR (SC) 201, SC made following observations: “The company is not a natural person. We are aware that in many recent penal statutes, companies or corporations are deemed to be offenders on the strength of the acts committed by persons responsible for the management of affairs of such company or corporations e.g. Essential Commodities Act, Prevention of Food Adulteration Act, etc. But there is no such provision in TADA, which makes the company liable for the acts of its officers. Hence, there is no scope whatsoever to prosecute a company for the offence under Section 3(4) of TADA. The corollary is that the conviction passed against A-12 is liable to be set aside.” In Standard Chartered Bank Vs. Vinay Kumar Sood & Ors, 2009 (1) JCC 756, this court had observed as under: “Undisputedly, the petitioner is a bank incorporated in England with limited liability by Royal Charter, 1853 and, therefore, is a corporation/company. A company cannot be in any case held to have committed an offence under Section 500 IPC because; most essential ingredient of the said offence i.e. ‘mens rea’ would be missing as a company is a juristic entity or an artificial person, whereas a Director is not a company. The company may be made liable for offences, however, if there is anything in the definition or context of a particular Section or a particular statute, which would prevent the application of the said section to a limited company, the limited company cannot be proceeded against. There are number of provisions of law in which it would be physically impossible by a limited company to commit the offence. A limited company, therefore, cannot generally be tried for offences where mens rea is essential. Similarly, a company cannot face the punishment of imprisonment for obvious reasons that company cannot be sent to prison by way of a sentence.” 5. The offence of criminal negligence requires a specific state of mind in respect of the person committing the offence. The offence of medical criminal negligence cannot be fastened on the company since the company

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can neither treat nor operate a patient of its own. It is the Doctor working in the company who treats and performs operations. It is the Doctor who examines the patients and prescribes medicines. If there is a deliberate or negligent act of the Doctor working in the Corporation/Hospital, it is the liability of the Doctor and not of the Corporation for criminal negligence despite the fact that due to the act of the Doctor of treating patients the Corporation was getting some revenue. These days, all Doctors with big hospitals, are on panels where they have fixed fee for examination of patients and for conducting operations. Out of this fee, a percentage is paid to the hospital. The hospital/ company cannot be held liable for the personal negligence of the Doctor in giving wrong treatment. However, if there is an administrative negligence, or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable. But, in the case of medical negligence, which is personal to the Doctor who gave treatment, the Corporation would not be liable and it is the Doctor who can be indicted for medial criminal negligence. 6. I therefore, allow this petition in respect of the petitioner. The order passed by learned M.M. qua the petitioner is hereby quashed. Comments 1. Is an important judgment. 2. Needs to be read in totality. 3. Is applicable mainly for the criminal act and not for compensation purposes 4. A criminal negligence on the part of a resident will be the responsibility of the resident and not the hospital. 5. But a fault of a resident where compensation is awarded will have to be paid by the hospital as he is the full time salaried staff of that hospital. 6. The judgment lines “However, if there is an administrative negligence, or a negligence of not providing basic infrastructure, which results into some harm to an aggrieved person or such negligence which is impersonal, the hospital can be held liable” Covers a lot of situations. A mistake by the nurse, resident, pathology services, radiology services, etc. will come under the “providing basic infrastructure services”.


emedinews inspiration

The Tiger’s Whisker

O

nce upon a time, a young wife named Yun Ok was at her wit’s end. Her husband had always been a tender and loving soul mate before he had left for the wars but, ever since he returned home, he was cross, angry and unpredictable. She was almost afraid to live with her own husband. Only in glancing moments did she catch a shadow of the husband she used to know and love. When one ailment or another bothered people in her village, they would often rush for a cure to a hermit who lived deep in the mountains. Not Yun Ok. She always prided herself that she could heal her own troubles. But this time was different. She was desperate. As Yun Ok approached the hermit’s hut, she saw the door was open. The old man said without turning around: “I hear you. What’s your problem?” She explained the situation. His back still to her, he said, “Ah yes, it’s often that way when soldiers return from the war. What do you expect me to do about it?” “Make me a potion!” cried the young wife. “Or an amulet, a drink, whatever it takes to get my husband back the way he used to be.” The old man turned around. “Young woman, your request doesn’t exactly fall into the same category as a broken bone or ear infection.” “I know”, said she. “It will take three days before I can even look into it. Come back then.” Three days later, Yun Ok returned to the hermit’s hut. “Yun Ok”, he greeted her with a smile, “I have good news. There is a potion that will restore your husband to the way he used to be, but you should know that it requires an unusual ingredient. You must bring me a whisker from a live tiger.” “What?” she gasped. “Such a thing is impossible!” “I cannot make the potion without it!” he shouted, startling her. He turned his back. “There is nothing more to say. As you can see, I’m very busy.” That night Yun Ok tossed and turned. How could she get a whisker from a live tiger? The next day before dawn, she crept out of the house with a bowl of rice covered with meat sauce. She went to a cave on the mountainside where a tiger was known to live. She clicked her tongue very softly as she crept up, her heart pounding, and carefully set the bowl on the grass. Then, trying to make as little noise as she could, she backed away. The next day before dawn, she took another bowl of rice covered with meat sauce to the cave. She approached the same spot, clicking softly with her tongue. She saw that the bowl was empty, replaced the empty one with a fresh one, and again left, clicking softly and trying not to break twigs or rustle leaves, or do anything else to startle and unsettle the wild beast. So it went, day after day, for several months. She never saw the tiger (thank goodness for that! she thought) though she knew from footprints on the ground that the tiger - and not a smaller mountain creature - had been eating her food. Then one day as she approached, she

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noticed the tiger’s head poking out of its cave. Glancing downward, she stepped very carefully to the same spot and with as little noise as she could, set down the fresh bowl and, her heart pounding, picked up the one that was empty. After a few weeks, she noticed the tiger would come out of its cave as it heard her footsteps, though it stayed a distance away (again, thank goodness! she thought, though she knew that someday, in order to get the whisker, she’d have to come closer to it). Another month went by. Then the tiger would wait by the empty food bowl as it heard her approaching. As she picked up the old bowl and replaced it with a fresh one, she could smell its scent, as it could surely smell hers. “Actually”, she thought, remembering its almost kittenish look as she set down a fresh bowl, “it is a rather friendly creature, when you get to know it.” The next time she visited, she glanced up at the tiger briefly and noticed what a lovely downturn of reddish fur it had from over one of its eyebrows to the next. Not a week later, the tiger allowed her to gently rub its head, and it purred and stretched like a house cat. Then she knew the time had come. The next morning, very early, she brought with her a small knife. After she set down the fresh bowl and the tiger allowed her to pet its head, she said in a low voice: “Oh, my tiger, may I please have just one of your whiskers?” While petting the tiger with one hand, she held one whisker at its base and, with the other hand, in one quick stroke, she carved the whisker off. She stood up, speaking softly her thanks, and left, for the last time. The next morning seemed endless. At last her husband left for the rice fields. She ran to the hermit’s hut, clutching the precious whisker in her fist. Bursting in, she cried to the hermit: “I have it! I have the tiger’s whisker!” “You don’t say?” he said, turning around. “From a live tiger?” “Yes!” she said. “Tell me”, said the hermit, interested. “How did you do it?” Yun Ok told the hermit how, for the last six months, she had earned the trust of the creature and it had finally permitted her to cut off one of its whiskers. With pride she handed him the whisker. The hermit examined it, satisfied himself that it was indeed a whisker from a live tiger, then flicked it into the fire where it sizzled and burned in an instant. “Yun Ok”, the hermit said softly, “you no longer need the whisker. Tell me, is a man more vicious than a tiger? If a dangerous wild beast will respond to your gradual and patient care, do you think a man will respond any less willingly?” Yun Ok stood speechless. Then she turned and stepped down the trail, turning over in her mind images of the tiger and of her husband, back and forth. She knew what she could do.


eMedi Quiz

Quiz Time 1.

The symptoms of toxic oil syndrome most closely resemble, which dermatologic disease?

A. SLE B.

Panniculitis

C.

Scleroderma

D. Giving the neonate only glucose water for the first 24 hours 4.

D. Dermatomyositis 2.

The inherited deficiency of which enzyme is responsible for the fish odor syndrome?

A. Trimethylamine oxidase B.

Trimethylamine reductase

C.

Flavin monooxygenase

A. Neonates: 10.6-16.5 g/dl B.

3 months: 10.6-16.5 g/dl

C.

3 years: 9.4-15.5 g/dl

D. 10 years: 10.7-15.5 g/dl 5.

D. Choline esterase 3.

Dr Smith suspects tracheoesophageal fistula in a 1-day-old neonate. Which nursing intervention is most appropriate for this child?

A. Avoiding suctioning unless cyanosis occurs

When caring for children who are sick, who have sustained traumas or who are suffering from nutritional inadequacies, nurse Ron should know the correct hemoglobin (Hb) values for children. Which of the following ranges would be inaccurate?

A female client is admitted for treatment of chronic renal failure (CRF). Nurse Juliet knows that this disorder increases the client’s risk of:

A. Water and sodium retention secondary to a severe decrease in the glomerular filtration rate. B.

A decreased serum phosphate level secondary to kidney failure

B.

Elevating the neonate’s head and giving nothing by mouth

C. An increased serum calcium level secondary to kidney failure.

C.

Elevating the neonate’s head for 1 hour after feedings

D. Metabolic alkalosis secondary to retention of hydrogen ions.

Answers to eMedi Quiz Published in August 2013 Issue Q1. (c) Oxidation-mediated injury of the vascular endothelium Q2. (b) Fluid overload Q3. (c) Bacteria are absent on urine culture Q4. (d) All the above

Send your answers to the Editor-Indian Journal of Clinical Practice. E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP.

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

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lighter reading

Make Sure

During Medical Practice A patient of gross ascites presents with complaints of difficulty in breathing on lying down.

Oh my God! Why did you drain so much ascitic fluid?

Quote

Lighter Side of Medicine Mediocrity knows nothing higher than itself, but talent instantly recognizes genius.

—-Arthur Conan Doyle, Sr.

Mind Trivia 1. What is this word? c o n

Make sure to evaluate the patient thoroughly and only moderately tap the ascitic fluid since overenthusiastic tapping can be life-threatening. KK Aggarwal

Situation: A patient came with category 4 gallbladder disease (typical biliary symptoms but without gallstones on ultrasound).

©IJCP Academy

you need further evaluation for functional gallbladder disorder

Lesson: Category 4 patients with biliary colic but no gallstones detected after a

thorough evaluation for both biliary and non-biliary causes of their pain should be evaluated for functional gallbladder disorder, as patients with functional gallbladder disorder often respond to cholecystectomy. If the evaluation for functional gallbladder disorder is negative, patients are generally treated for functional dyspepsia or irritable bowel syndrome. Dr KK Aggarwal

396

unf (_ _ _ ) est

to (_ _ _) tures

hic (_ _ _) ful

eit (_ _ _) etic

ILLUSION

Dr. Good & Dr. Bad

Nothing can be done

Ans. (1) Condescending (2) unfold - oldest, topic - pictures, hiccup - cupful, either - heretic.

©IJCP Academy

2. Below are incomplete words. Place three (3) letters in each bracket so that you can complete the word on the left and begin the word on the right. Good luck.

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013


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 –

– –

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.

All pages should be numbered consecutively beginning with the title page.

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. –

Do not use clips/staples on photographs and artwork.

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. –

398

The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013

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


Indian Journal of Clinical Practice, Vol. 24, No. 4, September 2013


R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi


Ijcp September 2013