October 2016 by ejima

Volume 114 u Number 10 u Kolkata u October 2016

WORLD LAPAROSCOPY HOSPITAL D. MAS Diploma in Minimal Access Surgery

F. MAS Diploma in Minimal Access Surgery

FICRS Fellowship of International College of Robotic Surgeons

Fellowship & Diploma in Laparoscopic & Robotic Surgery University Recognised Hands-on Course for Surgeon & Gynaecologist

For Prospectus and Admission Contact : Cyber City, DLF Phase-II, Gurgaon, NCR Delhi, Ph. : 9540993399 | Email : admission@laparoscopyhospital.com Website : www.laparoscopyhospital.com 1

OCTOBER 2016

Vol 114 No. 10

Dr S S Agarwal

Dr K K Aggarwal

Dr Debasish Mukherjee

Dr Santanu Sen

National President, IMA

Honorary Secretary General, IMA

Honorary Editor, JIMA

Honorary Secretary, JIMA

Volume 114 u Number 10 u Kolkata u October 2016

CONTENTS Editorial : u Sudden Hearing Loss — Cause, Diagnosis & Management — Debasish Mukherjee .......................7 Originals and Papers : u Burden of risk factors and vulnerability to coronary heart disease in slum population of urban Patna — Rashmi Singh, Madhumita Mukherjee, Rajeev Kumar, Ritu Singh .......................9 Practitioners’ Series : u Evaluation of clinical efficacy and safety of lactitol versus lactulose in the treatment of constipation — Santhosh Kumar M, Bopanna I C, Durai P, Latha Reddy R, Ramalingaiah A, Ravi H B, Ravindra Kumar, Sathyanarayana S V, Shankarlingaiah S C, Vijayaraghavan ..............................................................14 u To study the status of free radicals and oxidative stress (superoxide dismutase activity) and the role of antioxidants (tocopherol and ascorbic acid) in the patients of Epilepsy — Chandrapal Singh, Paritosh Tiwari ............................................................................18 GP Forums : u Prevalence of hypertension in children in a rural population of North India — a population based study — Rajeev Bhardwaj, Arvind Kandoria, Rajeev Marwah, Piyush Vaidya, Bakshish Singh, Pravesh Dhiman, Avinash Sharma ........................23 u Study of bone mineral density and it’s correlation with serum estradiol level in postmenopausal women — Manjari Sinha, Pratiksha Gupta, Pushpa Bhatia, Sudhir K Kapoor ......................................................................................................25 Case Notes : u Tumoral mycetoma thigh without overlying sinuses — an unusual presentation — S S Rathore, Mohan Lal, Anil Kumar .........................................................................29 u Acute intermittent porphyria : diagnostic and therapeutic challenges in India — Rupal V Dosi, Rushad D Patell, Gundurao alias Harsh M Joshi, Purav C Shah.............................31 u Repeated pregnancy outcome in a case of takayasu arteritis — Subesha Basu Roy, Shilpa Basu Roy ..............................................................................................33 u Torsade de pointes complicating congenital complete atrioventricular block in a pregnancy with pre-eclamptic toxaemia — Ajay Mishra, Kishor Viradiya .....................................34 Pictorial CME : u Caput medusae with cruveilhier- baumgarten murmur : a syndrome of clinical significance — Laxmi Nand, Dhiraj Kapur, Atul Mahajan, YP Sharma.............................................36 Book Review ...............................................................................................................................................36 22

Vol 114 No. 10

OCTOBER 2016

IMA PRAYER

Vol 114 No. 10

OCTOBER 2016

FLAG SALUTATION

May everybody be happy

We, the members of Indian Medical Association Stand here to salute our National Flag. Its honour and glory shall be our light and strength And its course shall be our course. We pledge our allegiance to it And realizing our responsibilities as the accredited members of this national organization, We swear We will dedicate everything in our power To see it fly high in the comity of nations. JAI HIND LONG LIVE IMA!

May every one of us see to it That nobody suffers from any pain or sorrow I do not ask for crown Nor I wish to be in Heaven or reborn I only want to alleviate the suffering of those people Who are burning in fire of sorrow http://www.ima-india.org/ima/left-side-bar.php?scid=14

Office bearers for the year 2015-16 IMA Headquarters Dr SS Agarwal (National President) Prof (Dr) A Marthanda Pillai (Imm Past National President) Dr Shailendra N Vora (National Vice President) Dr K Prameela Surender Rao (National Vice President) Dr Om Parkash Singh Kande (National Vice President) Dr Sharad Kumar Agarwal (National Vice President) Dr KK Aggarwal (Hony. Secretary General) Dr RN Tandon (Hony. Finance Secretary) Dr Rajeev Ardey (Hony. Jt. Secretary) Dr Ravi Malik (Hony. Jt. Secretary), Dr Ramesh Kumar Datta (Hony. Jt. Secretary) Dr Sanjoy Banerjee (Hony. Jt. Secretary, Calcutta) Dr Pravin Gogia (Hony. Jt. Secretary) Dr Hans Raj Satija (Hony. Asst. Secretary) Dr Manjul Mehta (Hony. Asst. Secretary) Dr Harish Gupta (Hony. Jt. Fin. Secretary) Dr Ujjwal Kr Sengupta (Hony. Jt. Fin. Secretary, Calcutta) IMA CGP DrVinod Kumar Monga (Dean of Studies) Dr A Raja Rajeshwar (Hony. Secretary)

IMA AMS Dr Kranshankar W Deoras (Chairman) Dr Pullarao Pasumarthy (Hony. Secretary)

IMA NSS Scheme Dr Kirti M Patel (Chairman) Dr Yogendra S Modi (Hony. Secretary)

IMA AKN Sinha Institute Dr Shivkumar Utture (Hony. Director) Dr Arbind Kumar Sinha (Hony. Executive Secretary)

IMA NPP Scheme Dr Krishna M Parate (Chairman) Dr Jayairishnan A V (Hony. Secretary)

JIMA Dr Debasish Mukherjee (Hony. Editor) Dr Ranjan Kumar Chakraborty (Hony. Assoc. Editor) Dr Minakshi Gangopadhyay (Hony. Assoc. Editor) Dr Santanu Sen (Hony. Secretary) Dr Sukomol Das (Hony. Asst. Secretary)

IMA Hospital Board of India Dr RV Asokan (Chairman) Dr Ravi Wankhedkar (Hony. Secretary) Dr Anil S Pachnekar (HQs. Secretary)

Your Health Dr Amitabha Bhattacharya (Hony. Editor) Dr Rahul Dutta (Hony. Secretary) Apka Swasthya Dr Prabhat Kumar Tewari (Hony. Editor) Dr Arvind Singh (Hony. Secretary)

IMA National Health Scheme Dr Ashok S Adhao (Chairman) Dr Alex Franklin (Hony. Secretary) IMA National Pension Scheme Dr Sudipto Roy (Chairman) Dr KV Devadas (Hony. Secretary)

OCTOBER 2016

Vol. 114 No. 10

Editorial Sudden Hearing Loss — Cause, Diagnosis & Management

efinitions of sudden hearing loss have been based on severity, time course, audiometric criteria, and frequency spectrum of the loss. Abrupt as well as rapidly progressive losses have been included under a single definition of sudden hearing loss. Awakening with a hearing loss, Dr Debasish Mukherjee hearing loss noted over a few days, selective low- or high-frequency loss, and distortions in speech MBBS, DLO, MS perception have all been classified as sudden hearing losses. A commonly used criterion to qualify for Honorary Editor, JIMA this diagnosis is a sensorineural hearing loss of greater than 30 dB over 3 contiguous pure-tone frequencies occurring within 3 days’ period. Fortunately, the vast majority of cases of sudden hearing loss are unilateral, and the prognosis for some recovery of hearing is good. Usually it presents as unilateral loss of hearing; bilateral involvement is rare, and simultaneous bilateral involvement is very rare. Sudden deafness or sudden sensorineural hearing loss (SNHL) has many possible etiologies. Pathophysiology — The postulated pathophysiology for idiopathic sudden sensory hearing loss (ISSHL) has 4 theoretical pathways, as follows : Labyrinthine viral infection, Labyrinthine vascular compromise, Intracochlear membrane ruptures, Immune-mediated inner ear disease. A disease process involving any of these theoretical possibilities could have sudden hearing loss as a symptom. Each theory may explain a fraction of the episodes of sudden sensory hearing loss, but none of the existing theories individually could account for all episodes. Viral infection — The evidence to implicate viral infection as one cause of sudden idiopathic sensory hearing loss is circumstantial. Studies of patients with ISSHL show a moderate prevalence of recent viral-type illness. Sometimes, evidence of recent viral seroconversion or inner ear histopathology consistent with viral infection is present. The weakest of these links is the history of a recent viral illness. Noncontrolled studies report that 17-33% of patients recall a recent viral illness. Should those numbers seem significant, 25% of patients without hearing loss visiting an otolaryngology clinic had experienced a virallike illness within a month. Comparing patients experiencing ISSHL with control patients has produced some evidence of viral seroconversion. Rates of seroconversion for the herpesvirus family were significantly higher in the population of patients with sudden hearing loss. Finally, temporal bone histopathologic studies of patients who experienced ISSHL found damage in the cochlea consistent with viral injuries. Loss of hair cells and supporting cells, atrophy of the tectorial membrane, atrophy of the stria vascularis, and neuronal loss were observed. These patterns were similar to findings in documented cases of hearing loss secondary to mumps, measles, and maternal rubella. Viral infection can be implicated as a cause of ISSHL, but this cannot, as yet, be proven. Infections with mumps virus provide the best model for a virally induced sensorineural hearing loss. In one study of ISSHL, subclinical mumps infections were documented in 9 of 130 patients by positive immunoglobulin M (IgM) mumps antibodies. Vascular compromise — The cochlea is an end organ with respect to its blood supply, with no collateral vasculature. Cochlear function is exquisitely sensitive to changes in blood supply. Vascular compromise of the cochlea due to thrombosis, embolus, reduced blood flow, or vasospasm seems to be a likely etiology for ISSHL. The time course correlates well with a vascular event, a sudden or abrupt loss. A reduction in oxygenation of the cochlea is the likely consequence of alterations in cochlear blood flow. Alterations in perilymph oxygen tension have been measured in response to changes in systemic blood pressure or intravascular carbon dioxide partial pressure (pCO2). Histologic evidence of cochlear damage following occlusion of the labyrinthine vessels was documented in temporal bone studies in animals and humans. Intracochlear hemorrhage was noted as an early development; subsequently, fibrosis and ossification of the cochlea evolved. In one study, a partial overlap was found between classical coronary risk factors and risk factors for sudden hearing loss. Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) were not found to be apparent major risk factors for sudden hearing loss, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking were associated with an increased risk for ISSHL. In contrast to the above study, a historical prospective cohort study by Chang et al indicated that hypercholesterolemia is associated with an increased risk for idiopathic sudden sensorineural hearing loss (ISSNHL). Comparing nearly 74,000 patients with hypercholesterolemia with the same number of age-matched controls, the investigators found the incidence of ISSNHL to be 1.62 times greater in the hypercholesterolemia group. Altogether, the various study findings suggest a vascular involvement in the pathogenesis of ISSHL. This may have important implications for the development of therapeutic and preventive strategies for ISSHL. Intracochlear membrane rupture Thin membranes separate the inner ear from the middle ear, and within the cochlea, delicate membranes separate the perilymphatic and endolymphatic spaces. Rupture of either or both sets of membranes theoretically could produce a sensory hearing loss. A leak of perilymph fluid into the middle ear via the round window or oval window has been postulated to produce hearing loss by creating a state of relative endolymphatic hydrops or by producing intracochlear membrane breaks. Rupture of intracochlear membranes would allow mixing of perilymph and endolymph, effectively altering the endocochlear potential. The theory of intracochlear membrane rupture was favored by Simmons and Goodhill, and histologic evidence has been documented by Gussen. Immune-mediated inner ear disease — Sensorineural hearing loss induced by an immune process has gained greater and greater 6

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

notoriety since the concept was introduced in 1979. Progressive sensorineural loss is observed with this condition. Whether or not sudden hearing loss occurs with immune-mediated inner ear disease is unclear, but immunologic activity in the cochlea is supported by greater and greater evidence. The association of hearing loss in Cogan syndrome, systemic lupus erythematosus, and other autoimmune rheumatologic disorders has been well documented. With better markers for inner ear autoimmunity, perhaps a greater linkage with ISSNHL will be found. A recent prospective study on 51 patients with ISSNHL supported the existence of multiple immunemediated disorders in these patients. Iron-deficiency anemia — A study by Chung et al indicated that iron-deficiency anemia increases the risk for sudden sensorineural hearing loss. The report, which involved about 4000 persons with sudden sensorineural hearing loss and approximately 12,000 controls, found that 4.3% of the group with hearing loss had previously been diagnosed with iron-deficiency anemia, compared with 3.0% of the control group. The link between hearing loss and anemia seemed to be strongest in persons aged 44 years or younger. • Epidemiology • Frequency • United States Estimates of the annual incidence of sudden sensory hearing loss range from 5-20 cases per 100,000 persons. Many cases likely go unreported, and the incidence may be higher. A sudden hearing loss may resolve before the patient can be evaluated medically, making it unlikely for that individual to seek care. Sex — The female-to-male distribution appears to be equal. Combined data from several studies show a slight male preponderance, at 53%. However, a single large study of 1220 patients had slightly more females. Sex does not seem to be a risk factor. An equal distribution of right- and left-sided cases should be expected. As with sex, no greater risk for right-sided losses compared with left-sided losses seems to exist. Bilateral sudden hearing loss occurs in approximately 1-2% of cases. Age — People of all age groups are affected by sudden hearing loss, but fewer cases are reported in children and the elderly. The peak incidence appears to be in the sixth decade of life. Young adults have incidence rates similar to those of middle-aged adults. The median age at presentation ranges from 40-54 years. The occurrence of sudden hearing loss across all age groups is an indication of the multifactorial nature of this clinical problem. A literature review by Sara et al indicated that the onset of bilateral sudden sensorineural hearing loss tends to occur at a younger age than the unilateral form. What are the symptoms of SSHL ? You may notice hearing loss right after you wake up in the morning. You may also become aware of it when you use headphones or hold a phone to your affected ear. Sudden hearing loss is sometimes preceded by a loud popping sound. Other signs include : • Trouble following group conversations • Muffled conversation sounds • Inability to hear well when there’s a lot of background noise

• • • •

Difficulty hearing high-pitched sounds Dizziness Balance problems Tinnitus, which occurs when you hear ringing or buzzing sounds in your ear Nine out of 10 people with SSHL experience hearing loss in only one ear. How is SSHL diagnosed ? To diagnose SSHL, your doctor will ask you about your medical history and perform a physical exam. Make sure to tell your doctor about other medical conditions you may have and about any overthe-counter and prescription medications you’re taking. During the physical exam, you may be asked to cover one ear at a time while listening to various sounds at different volumes. Your doctor may also perform some tests using a tuning fork, which is an instrument that can measure vibrations in the ear. These tests can check for damage to the parts of the middle ear and eardrum that vibrate. Audiometry tests may be done to check your hearing more thoroughly and precisely. During these tests, an audiologist will test your hearing ability using earphones. A series of different sounds and volume levels may be sent to each ear individually. This can help determine the level at which your hearing begins to fade. An MRI scan may also be ordered to look for any abnormalities in your ear, such as tumors or cysts. The imaging test will take detailed pictures of your brain and inner ear, which can help your doctor find the underlying cause of SSHL. How is SSHL treated? Early treatment may increase your chances for a full recovery. However, your doctor will try to find the cause of your hearing loss before starting treatment. Steroids are the most common treatment. They can reduce inflammation and swelling. This is especially helpful in people who have diseases of the immune system, such as Cogan’s syndrome. Your doctor may also prescribe antibiotics if your SSHL was caused by an infection. In some cases, a cochlear implant can be surgically inserted into your ear. This implant doesn’t completely restore hearing, but it can amplify sounds to a more normal level. Outlook for People with SSHL About two-thirds of people with SSHL will experience partial recovery of their hearing. One study found that 54.5 percent of people with SSHL showed at least partial recovery in the first 10 days. The recovery is more complete among individuals who experience either high- or low-frequency hearing loss, as opposed to those whose hearing loss is across all frequencies. Only about 3.6 percent of people with SSHL will fully recover their hearing. There is less chance of recovery among older adults and those with vertigo. Hearing aids and telephone amplifiers can help if your hearing doesn’t improve. Sign language and lip reading can also improve communication for people with severe hearing loss.

Originals and Papers Burden of risk factors and vulnerability to coronary heart disease in slum population of urban Patna Rashmi Singh , Madhumita Mukherjee , Rajeev Kumar , Ritu Singh 1

Coronary Heart Diseases (CHDs), a major cause of disability and death are showing an increasing trend. Conventionally they are regarded as diseases of affluence and lifestyle. There are adverse effects on the economy if the productive segments of the population is affected. Objective: To assess the magnitude of risk factors of CHDs in the poorer population segment of urban slum. Methods: This was a population based cross sectional study conducted in the slums of urban Patna among the persons above 30 years of age to assess the risk factors of CHDs. Results: Out of a total of 3118 (1357 male & 1761 female) participants, 16.36 percent (95percent CI 15.62 – 17.1) were hypertensive; 26.3 percent (95percent CI 25.42 – 27.18) had elevated random capillary blood glucose (RCBG) and 4.46 percent had symptoms of Diabetes mellitus. Overall, high body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR) was noted in 31.98 percent, 50.45 percent and 86.53 percent respectively; 33.64 percent were sedentary, 12.54 percent and 9.14 percent reported use of tobacco and alcohol respectively. Hypertension was significantly associated with high BMI, WC, WHtR and tobacco use. Further, high RCBG was significantly associated with high BMI. Conclusion: There is notable load of CHD risk factors in slum population of Patna. This is a matter of concern as urban poor already have the burden of communicable diseases, hence the necessity of including them in the ambit of preventive care and intervention cannot be overemphasized. [J Indian Med Assoc 2016; 114: 9-13]

Key words : Coronary Heart Diseases, Urban Slums, Risk Factors.

In planning of health services, the priority is generally given to the vast rural population with a focus on the communicable diseases and maternal and child health problems. National urban health mission is yet to roll out; the growing urban poor are yet to receive attention.

orld Health Report (WHO) 2002 predicts that by 2020 AD, cardiovascular diseases (CVDs) will be the leading cause of death and disability. In India, 2.6 million are predicted to die of coronary heart disease (CHD) comprising 54.1 percent of all CVD deaths; half of CHD deaths will be in the age range of 30-69 years. Overall economic growth and globalization have helped surfacing of CHDs even in the developing countries where they were conventionally labelled as the diseases of affluence . The section of urban poor is escalating in the developing world due to migration of rural population who have to bear the stress of urban lifestyles with the underprivileged economy and poor health care delivery services. Health hazards of urban slum dwellers are directly related to poverty, pollution and stressful environment. CHDs are emerging as major public health problems. With the increase in urban population of India to 31.80 percent, 22.76 percent now dwell in urban slums; urbanization is expected to rise to 50 percent by 2021 and the proportion of urban poor will double in 5 years .

Few studies have been done on health of slum dwellers in India, but none in Bihar. This study was undertaken to get baseline data of health of urban poor living in the slums of Patna especially in reference to risk factors of CHDs.

1,2

MATERIAL AND METHOD

This was a cross sectional observational study to obtain baseline data on the CHD risk factors among slum population of Patna. It focused on diabetes and hypertension, Body Mass Index (BMI), Waist Circumference (WC). Waist Height ratio (WHtR), use of tobacco and alcohol and physical inactivity as risk factors of CHD. A list of 90 approved slums of Patna was obtained from Municipal Corporation, Patna. Two teams consisting of 3 doctors and paramedics each were trained at Patna Medical College to conduct health checkups including anthropometric, blood pressure and random capillary blood glucose (RCBG)

3-5

Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. JIMA assumes no responsibility for the authenticity or reliability of any product, equipment, gadget or any claim by medical establishments/institutions/manufacturers or any training programme in the form of advertisements appearing in JIMA and also does not endorse or give any guarantee to such products or training programme or promote any such thing or claims made so after. — Hony Editor

Department of Community Medicine, Patna Medical College, Patna 800004 1 MBBS, MD, Professor and Head 2 MBBS, MD, Tutor 3 MBBS, Jr Resident 4 MBBS, Field Investigator 9

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

measurements. The 2 teams visited all the 90 slums consecutively on prefixed days to conduct health checkups in camp setting. Each camp was preceded by field visits and health education activities to motivate the slum dwellers to avail the facilities of the health camps and participate in study. Study population: All adults above 30 years of age attending health camps. Exclusion criteria: Persons below the age of 30 years, seriously ill and nonconsenting. Data collection procedure: On the prefixed dates, the health teams from Patna Medical College visited the slum. Informed consents were obtained from the participants. Then socio-demographic data, details of personal life styles including consumption of tobacco in any form or alcohol intake and their duration were recorded in a pretested questionnaire followed by clinical examinations, anthropometry, blood pressure and RCBG measurements. Those who screened positive with undiagnosed hypertension, hyperglycemia and or diabetes were referred to Patna Medical College for further evaluations. Case definitions used were those of WHO STEPS Manual: for exercise, alcohol users and smokers . Heights were recorded to the nearest centimeters (cms) using portable height measuring stand; weights were recorded using standard bathroom scales; waist circumference was measured using flexible nonstretchable measuring tape in standing position. Blood pressures were taken by mercury sphygmomanometer as per JNC 7 criteria and was considered positive if the systolic blood Pressures (SBP) of > 140 mmHg and or diastolic blood pressures (DBP) of >90 mmHg or if they reported previous diagnosis of hypertension . Random capillary glucometer blood tests were performed by finger prick method irrespective of the time of food intake and blood glucose was measured by On Call Plus glucometer of ACON Laboratories, India. The random capillary blood glucose (RCBG) was taken positive > 140 mg/ dl (7.8 mmol/l) based on WHO diabetes diagnostic criteria to distinguish a group with significantly increased premature mortality and increased risk of microvascular and cardiovascular complications . This value of RCBG has the same sensitivity and specificity as venous blood to discriminate prediabetics with impaired glucose tolerance test . With the reported specific symptoms of diabetes, those with RCBG > 200 mg/ dl (11.1 mmol/l) and any one of the classic symptom or weight loss were also diagnosed as positive cases of diabetes mellitus . BMI was calculated by the standard formula of weight in kg / height in m and > 25 was taken as cut off. Waist circumference (WC) of more than 90 cms in males and 80 cms in females respectively were taken as cut off . Waist to height ratio (WHtR) was calculated by waist circumference (WC) in cm / height in cm; cut offs for high WHtR were > 0.48 in males and >0.45 in females . 6

BURDEN OF RISK FACTORS AND VULNERABILITY TO CORONARY HEART DISEASE — SINGH ET AL

Statistical analysis: Data were entered into Excel spreadsheets Percentages and proportions were used to analyze the risk factors using SPSS Version 17.

Table 1 — Showing age & sex distribution of subjects with hypertension and elevated RCBG Male =1357

OBSERVATIONS

Of the 3118 subjects, 1357 (43.52%) were males and 1761 (56.48%) females. Age breakup revealed largest number of males in 50 – 59 age group (25.06%) whereas largest number of females were in the 40 - 49 years (28.28%). Overall, hypertension was present in 16.36 percent (95% CI 15.62 – 17.1); 18.79 percent in males 14.48 percent in females. Age and sex wise, highest number of hypertensives were males in the age group of 50 – 59 years (5.82%); for females it was in 40-49 age group (4.32%). Elevated RCBG levels (> 140 mg/ dl 7.8 mmol/l); was noted in 26.3 percent (95% CI 25.42 – 27.18) subjects, of which 25.94 percent were males and 26.58 percent females; largest proportion of males were in age group of > 60 years and females in the 40 – 49 year age group. Using the criteria of elevated RCBG levels > 200 mg/ dl (11.1 mmol/l) and presence of any of the classic symptom, 4.46 percent of the study participants were labeled as diabetic. (Table 1) BMI was high in 996 (31.94 %); 432 (31.83%) males and 564 (32.03% ) females. WC was higher in 1573 (50.45%), out of which 531 (39.1%) were males and 1042 (59.17%) females. WHtR were higher in 2698 (86.53%); 1128 (83.12%) in male and 1570 (89.15%) in female. Usage of tobacco in any form was 391 (12.54 %); higher in males (21.15 %) than females (5.91 %). Alcohol users were 285 (9.14 %); 226 (16.65 %) were males and only 59 (3.35 %) were females. In lifestyles, 1049 (33.64 %) were sedentary and physically inactive; 538 (30.55%) males and 511 (37.65%) females. (Table 2) A significantly higher BMI was noted in hypertensive as compared to normotensive (χ = 17.329, P value = 0.000). A significantly higher WC was found in both males and females with hypertension as compared to normotensive (χ = 19.57, 15.01 respectively; P value = 0.000). There was significant association in both males and females (p < 0.0001) with hypertension and their WHtR. Hypertension was also associated with the lifestyle factors of the tobacco, alcohol use and also physical inactivity (c =23.34, 27.80, 2.64, P Value 0.000) High RCBG levels were significantly associated with BMI (χ = 5-78, P value =.014) but not with WC, WHtR, tobacco, alcohol use or lifestyle. (Table 3) 2

DISCUSSION

This CHD risk factor study was carried out in a hitherto poorly studied urban setting of the lowest socioeconomic strata spread across 90 wards of Patna Municipal Area. The study subjects, mostly rural migrants who had come to Patna for economic reasons and were residing in the slums showed a marked prevalence hypertension and

Female =1761 Elevated Blood Sugar (mg/dl) (>140)

Age No of Group subjects (percent)

HTN No of subjects (percent)

30-39 40-49 50-59 >= 60 Total

41 (3.02) 37 (2.73) 71 (5.23) 64 (4.72) 79 (5.82) 52 (3.83) 64 (4.72) 67 (4.94) 255 (18.79) 220 (16.21)

293 (21.59) 411 (30.29) 340 (25.06) 313 (23.07) 1357 (100)

140 – 200 No of subjects (percent)

> 200 No of subject (percent)

Total No of subject (percent)

Elevated Blood Sugar (mg/dl) (>140) Age Group

7 (0.52) 44 (3.24) 30-39 34 (2.51) 98 (7.22) 40-49 47 (3.46) 99 (7.30) 50-59 44 (3.24) 111 (8.18) >= 60 132 (9.73) 352 (25.94) Total 63* (4.64)

No of subject (percent)

HTN No of subject (percent)

140 – 200 No of subject (percent)

575 (32.65) 55 (3.12) 80 (4.54) 498 (28.28) 76 (4.32) 114 (6.47) 348 (19.76) 60 (3.41) 65 (3.69) 340 (19.31) 64 (3.63) 72 (4.09) 1761(100) 255(14.48) 331(18.80)

> 200 No of subject (percent)

Total No of subject (percent)

15 (0.85) 36 (2.04) 41 (2.33) 45 (2.56) 137(7.78) 73* (4.15)

95 (5.39) 150 (8.52) 106 (6.02) 117 (6.64) 468(26.58)

* Also had classical symptoms of diabetes HTN = Hypertension RCBG = Random Capillary Blood Glucose

hyperglycemia and obesity indices. The study conducted BMI levels of >25 was significantly associated with both on a population of slum dwellers showed a 16.36 percent hypertension (HTN) and elevated blood glucose levels in prevalence of hypertension. Studies conducted in slums this study; similar results were observed in Indians living of Faridabad, Delhi and urban Chennai in lower in Mauritius who had increased rates of type 2 diabetes socioeconomic group reported a prevalence of 17.2, 12 and HTN at these BMI levels . Prevalence of diabetes and and 8.4 percent respectively . There is also a prevalence impaired glucose tolerance was lower in low income of 26.3 percent of elevated RCBS. According to the group (LIG) than high Income group (HIG); high BMI recommendation adopted by WHO in 1999 impaired was significantly associated with diabetes; hypertension glucose tolerance is a not clinical entity but rather a risk was more in LIG than HIG (53% versus 40% ). factor for future diabetes and adverse outcome . Studies of Hyperglycemia, dyslipidmia, hypertension, smoking and elevated RCBS were not found but in a similar study of alcohol consumption was more in LIG group . urban slum population prevalence of diabetes mellitus was In our study it was seen that the prevalence of central found to be 10.3 percent and in another study on railway employees it was found to be 7.57percent . In the studies reported from Chennai, RCBG cut points were also used to report and Table 2 — Showing distribution of subjects with high levels of Risk identify diabetes . Factors for Cardiovascular diseases 18

13-15

12,13

A limited no of studies have been done to assess the prevalence of CHD risk factors in this segment of the population. Prevalence of overweight and obesity was 31.94 percent in this study. In urban Chennai, Mohan et al reported 33percent prevalence of overweight and obesity in low income group and the prevalence increased with increase in income . Misra et al and ICMR Task force study reported a prevalence of 25 percent and 20 percent respectively in Delhi slums 14,17. 15

Parameters

Male =1357 n (percent)

Hypertension Elevated Random Capillary Blood Glucose (RCBG) Body Mass Index Waist Circumference Waist Height Ratio Tobacco Alcohol Physical Inactivity

255 (18.79)

255 (14.48)

510 (16.36)

352 (25.94) 432 (31.83) 531 (39.13) 1128 (83.12) 287 (21.15) 226 (16.65) 511 (37.65)

468 (26.58) 564 (32.03) 1042 (59.17) 1570 (89.15) 104 (5.91) 59 (3.35) 538 (30.55)

820 (26.30) 996 (31.94) 1573 (50.45) 2698 (86.53) 391 (12.54) 285 (9.14) 1049 (33.64)

HTN = Hypertension RCBG = Random Capillary Blood Glucose

Female = 1761 Total =3118 n (percent) n (percent)

BURDEN OF RISK FACTORS AND VULNERABILITY TO CORONARY HEART DISEASE — SINGH ET AL

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

Table 3 — Association of Risk Factors with Hypertension & Elevated RCBG Risk Factors

Association with HTN n (percent ) Statistical test p value 203 (39.80) χ = 17.329 Male – 183 χ = 19.57 (71.7%) Female – 127 χ = 15.01 (49.8%) 471 (92.35) χ = 26.92 97 (19.02) χ = 23.34 78 (15.29) χ = 27.801 36 (7.05) χ = 2.64 2

Body Mass Index Waist Circumference

Waist Height Ratio Tobacco Alcohol Physical Inactivity

Association with Elevated RCBG n (percent ) Statistical test p value

0.000* 0.000* 0.000* 0.000* 0.000* 0.000* 0.067

χ = 5.78 χ = .014

0.014* 0.906

χ = 4.258

0.139

χ = .913 χ = .010 χ = .174 χ = .640

0.172 0.919 0.677 0.424

290 (35.37) Male = 278 (59.4) Female = 154 (43.75) 721 (87.93) 102 (12.44) 72 (8.78) 283 (34.51)

*P-value<0.05 is significant. df = 1 for χ test 2

obesity indicators was higher in females as compared to males. Waist circumference more than 90 cm in males and 80 cm in females was taken to be a risk factor in for development of metabolic syndrome and measure of CHD risk . Recently there has been exponential increase in the evidence from other investigations showing the superiority of waist height ratio (WHtR) as a predictor of metabolic and cardiovascular risk based on studies in both adults and children . Using the International Diabetes Federation (IDF) criteria, waist circumference was high in 50.45 percent of the study population. Misra et al reports 12 percent and the ICMR Task Force 31percent in Delhi slums using higher cut offs . New research shows that WHtR and not BMI is a better assessment tool for diabetes & CHD risk and WHtR represents the best predictor of the risk and mortality . with a relative risk of 2.75 of cardiovascular mortality . WHtR was abnormal in 86.5percent in this study, it was 82percent in a study on anthropometric indices and coronary risk factors in a study on railway employees . Tobacco consumption in either smoky or chewable form was found to 12.54 percent in the study population which is less than the prevalence rate of 22.75percent in those above 15 years and both sexes and all social classes in Bihar . Several studies from developing countries have shown the presence of hypertension and other risk factors for CHDs in urban compared with rural populations . Based on available trends, by 2020 CVDs are predicted to account for 73 percent of deaths and 60percent of disease burden globally . WHO has developed guidelines for the identification of the magnitude and patterns of major risk factors by countries which is fundamental for their prevention of urban poor . The study at 8 purposively selected communities of Chandigarh and Haryana during 2004-05, on 400 adults 11

14,17

>or =30 years of age, selected by cluster sampling, the prevalence of hypertension was found in urban (39%; 95% CI 29.5%-49.2%), slum (35%; 95% CI 27.2%-42.9%) and rural (33%; 95% CI 25.4%-40.8%) communities was found to be statistically similar after controlling for age, gender and education. The prevalence of physical inactivity (17% versus 12%), central obesity (90% versus 88%), overweight (20% versus 19%) and hypertension (34% versus 36%), were found to be statistically similar among literate and illiterate population after controlling for the effect of age, sex and place of residence. However, the risk of tobacco use was significantly lower among literates (OR 0.3, 95% CI 0.1-0.8). The researchers concluded that in selected communities of northern India, most of the cardiovascular disease risk factors did not have a social gradient except tobacco use, which was more common in the lower social group . 26

20,21

In a cross-sectional survey conducted on male employees working in an urban industrial male population in Chennai the prevalence of the metabolic syndrome was 41.3% and 51.4% using IDF and AHA/NHLBI criteria respectively. Risk factors were age above 35 years, family history of diabetes and body mass index (BMI) above 23.9 kg/m2 . 27

A cross-sectional study was conducted on urban poor in New Delhi on 531 using the WHO STEPS-1 questionnaire. About 73 (13.7%) were known hypertensives; 40.3%) did not partake in any kind of specific physical activity . 28

In this study valuable baseline data on the health status of slum dwellers was obtained and it underlines the vulnerability of the slum dwellers to CHD risk and the necessity of interventions.. The health camp approach enrolled 3118 participants which probably would not have been possible by any other methodology, however other risk factors such as dietary intake and dyslipedemia

could not be studied. It also endorses the fact that the traditional categorization of CHDs as a diseases of affluence needs to be changed. The use of RCBG testing for screening of elevated blood glucose level has the advantage that it can be done at any time of the day. does not require venpuncture and can be carried out even by lay people with training. Though the association of these risk factors with disease is well established, there were no such studies in Bihar; more studies including multivariate analysis can be undertaken in future. The magnitudes of CHD risk factors in slum population of Patna is a matter of concern; there is necessity of including them in the ambit of preventive care and intervention. Since the poor also have the burden of communicable diseases, it could very well be that all major diseases are diseases of the poor. The finding of this study will assist in developing targeted programs and monitoring intervention on CHDs. ACKNOWLEDGMENT

We are grateful to State Health Society Bihar for giving us an opportunity to conduct this baseline study of the risk factors of coronary heart disease with particular focus on hypertension and hyperglycemia. The study was conducted as directed by Government of Bihar by Department of Community Medicine, Patna Medical College with logistic support of District Heath Society, and Civil Surgeon Patna. REFERENCES 1 National Cardiovascular Disease Database sticker no SE/04/233208 IC Health supported by Ministry of Health and Family Welfare and World Health Organization 2002. Available at www.whoindia.org/linkfiles/NMH resources. Accessed on 12/08/2011. 2 Cardiovascular diseases on a global scale: No longer a disease of the rich. Available at http://theheart.org/article/45381.do accessed on 20th Aug 2011. 3 Census of India 2011. Provisional Population Totals. Paper 2 Volume 1 of 2011 Rural-Urban Distribution India Series 1:7-8. Available at www.censusindia.gov.in accessed on 12 Aug 2011. 4 Census of India. 2001. Metadata and Brief Highlights on Slum Population. Available at www.censusindia.gov.in /Data_Products/Data_Highlights. accessed on 12/08/2011. 5 Planning commission 11th Five year plan (vol 2) :Government of India 2008:78-80. 6 WHO STEP wise approach to chronic disease risk factor surveillance. Available at www.who.int/chp/steps/en Accessed on 10th Nov 2010. 7 The 7th Report of National Committee on Prevention, Detection, Evaluation of high blood pressure. 2004; 11-18. Available at www.nhlbi.nih.gov/guidelines /hypertension/jnc-7 Accessed on 10th Nov 2010. 8 Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia 2005; Report of WHO/IDF Consultation:1-17 9 Somannavar S, Ganesan A, Deepa M, Datta M, Mohan V— Random Capillary Blood Glucose Cut point For Diabetes and Pre-Diabetes derived from Community Based Opportunistic Screening in India. Available at http://care.diabetesjournals.org/content/ early/2008/12/10/ accessed on 12th Aug 2010. 10 Kasper DL, Braunwald E, Fauci AS et al, Diabetes Mellitus,

11 12 13

17 18 19 20 21

23 24 25 26 27

Alvin C Powers Ed. Harrison’s Principles of Internal Medicine Vol II 17th ed. New York, NY:Mcgraw-hills, 2008; 2275-77. IDF consensus worldwide definition of the METABOLIC SYNDROME. International Diabetes Federation 2006; 7-11. Patil VC, Parale GP, Kulkarni PM. Patil HV. Relation of anthropometric variables to coronary artery disease risk factors. Indian J Endocn Metab 2011; 15: 31-7. Anand Shah B, Yadav K, Singh R, Mathur P, Paul E — Are the Urban poor vulnerable to non-communicable diseases? A survey of risk factors for non-communicable diseases in urban slums of Faridabad. Natl Med J India 2007; 20: 11520. Misra A, Pandey RM, Devi JR, Vikram NK, Khanna N — High prevalence of diabetes obesity and dyslipidimia in urban slum population of northern India. Int J Obes Relat Metab Disord 2001; 11: 1722-9. Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R — Intra urban differences in the prevalence of the metabolic syndrome in Southern India. The Chennai Urban population Study. (CUPS). Diabet Med 2001; 18: 280-7. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organization 1999:14-15 available at http://whqlibdoc.who.int/hq/1999/ who_ncd_ncs_99.2.pdf accessed on 10th Nov 2010. ICMR Task force project on collaborative study of coronary heart disease; National cardiovascular disease Database sticker no: SE/04/233208: 15-8. AC Bell, Linda S Adair, Barry M. Popkin. Ethnic difference in association between body mass index and Hypertension. Am J Epidemiol 2002; 155: 346-43. Ramchandra A, Snehalatha C, Vijay V, King H — Impact of poverty on prevalence of diabetes and its complications in urban southern India. Diabet Med 2002; 19: 130-5. Hsieh SD, Ashwell M, Muto T, Tsuji H, Arase Y, Murase T — Urgency of reassessment of role of obesity indices for metabolic risks. Metab Clin Exper 2010; 59: 834-40. Schneider HJ, Friedrich N, Klotsche J, Pieper L, Nauck M — The predictive value of different measures of obesity for incident cardiovascular events & mortality. J Clin Endocrinol Metab 2010; 95: 1777-85 Rani M, S Bonu, Jha P, SN Njuyen, L Jamjourm — Tobacco use in India: prevalence and predicators of smoking and chewing in a national cross sectional household survey . Tobaco Control 2003;12(4). Available at www.tobaccocontrol.com /cgi/content/full/ 12/4/ e4 Accessed on 28th Aug 2011 Reddy KS, Prabhakaran D, Shah P, Shah B — Differences in body mass index and waist: hip ratios in North Indian rural and urban populations. Obesity Reviews 2002; 3:197-202. Zimmet PZ, K George, Alberti MM. Globalization and Noncommunicable Disease Epidemic. Obesity 2006; 14(1). Nauru NCD Risk factors STEPS Report. 2006. Available at www.spc.int/prism/ country/nr/stats/publication/surveys. Accessed on 12/08/2011. Kar SS, Thakur JS, Virdi NK, Jain S, Kumar R — Risk factors for cardiovascular diseases: is the social gradient reversing in northern India? Natl Med J India 2010; 23: 206-9. Kaur P, Radhakrishnan E, Rao SR, Sankarasubbaiyan S, Rao TV, Gupte MD. The metabolic syndrome and associated risk factors in an urban industrial male population in South India. J Assoc Physicians India 2010; 58: 363-6, 371. Nath A, Garg S, Deb S, Ray A, Kaur R — A study of the profile of behavioral risk factors of non communicable diseases in an urban setting using the WHO steps 1 approach. Ann Trop Med Public Health 2009; 2: 15-9.

Practitioners' Series

EVALUATION OF CLINICAL EFFICACY AND SAFETY OF LACTITOL — KUMAR M ET AL

Primary causes of constipation can be classified into 3 groups:

Evaluation of clinical efficacy and safety of lactitol versus lactulose in the treatment of constipation 1

Santhosh Kumar M , Bopanna I C , Durai P , Latha Reddy R , Ramalingaiah A , Ravi H B , 7 8 9 10 Ravindra Kumar , Sathyanarayana S V , Shankarlingaiah S C , Vijayaraghavan

Constipation is a chronic problem occurring in all age groups and regularly seen by doctors of most specialties. Recently, lactitol - an osmotic laxative similar to lactulose, has been actively promoted and received acceptance in the treatment of constipation. It has been shown to have the advantage of being better tolerated and producing more predictable catharsis as compared to lactulose. The effect of these two osmotic laxatives was evaluated for the treatment of constipation in this post-marketing surveillance study conducted in 90 patients. Episodes of spontaneous bowel movement, side effects, palatability and patient’s acceptability were recorded for a period of seven days of treatment. During the study, the number of bowel evacuations per week was 9.302 ± 1.090 in lactitol group versus 7.209 ± 0.6857 in lactulose group (p>0.05). Lactitol was found to be significantly superior to lactulose in terms of less number of adverse reactions, 27.16 ± 3.923 % versus 42.93 ± 5.122 % (p<0.05). The patients inferred lactitol to have better response, found it to be more palatable and had better compliance as compared to lactulose group. We conclude that lactitol is as effective as lactulose with lesser side effect profile and patients satisfaction superior to lactulose in treatment of constipation. [J Indian Med Assoc 2016; 114: 14-7]

Key words : Constipation, osmotic laxative, lactitol, lactulose.

conducted in India, a literature review mentions the incidence of constipation to be around 15% in India . The incidence of constipation increases with age, and women are more likely to report constipation than men. This fact is particularly relevant when considering the additional risk of constipation in pregnant women with a prevalence as high as 11-38% .

onstipation is a symptom, not a disease and almost everyone experiences it at some point in their life with poor diet typically being the cause . Epidemiologic data on incidence of constipation vary considerably as a result of differences among diagnostic criteria, definition, dietary and cultural characteristics, subjectivity of self reports and patient population . Depending on these factors, constipation surveys show prevalence between 1% and more than 20% in the western population. In studies of the elderly population, up to 20% of community dwelling individuals and 50% of institutionalized elderly persons reported symptoms . Though there are no exact prevalence studies

Definition : Though constipation is a chronic problem in many patients all over the world, the terminology associated with constipation is problematic. The word constipation has several meanings and the way it is used may differ not only between patients but also among different cultures and regions . As per the Rome III Criteria for functional constipation; there is constipation if patients who do not take laxatives, fulfill the following two or more criteria with at least 25% of defecations for at least 3 months prior to baseline visit: Straining during defecations, Lumpy or hard stools, Sensation of incomplete evacuation, Sensation of anorectal obstruction/blockage, Manual maneuvers to facilitate defecations (eg, digital evacuation, support of the pelvic floor) and Fewer than three defecations per week .

MBBS, MD, Medical Advisor, Anglo-French Drugs & Industries Ltd, Bangalore 560010 2 MBBS, MS (Ortho), Consultant Orthopaedic Surgeon, Church of South India Hospital, Bangalore 560051 3 MBBS, FAIMS, MCCP, MRSH, G Dip (Diabetology), Consultant Diabetologist, SV Diabetes Centre, Chennai 600017 4 MBBS, MD, Physician, Sri Nagendra Clinic, Bangalore 560033 5 MBBS, MS (Ortho), Professor of Orthopaedic Surgery, Abhilash Orthopaedic Hospital, Bangalore 560085 6 MBBS, DVD, Dermatologist, Sridevi Clinic, Bangalore 560050 7 MBBS, DCH, Consulting Pediatrician, Bangalore Diagnostic Centre, Bangalore 560084 8 BSc, MBBS, D ORTH, MS (Ortho), MNAMS, FICS, Senior Consultant Orthopaedic Surgeon, Chennai 600024 9 MBBS, MD, Physician, Clinic #2017/A, Bangalore 560040 10 MBBS, Physician, Life Span Clinic, Chennai 600017

Causes : The etiology of constipation is usually multifactorial, but it can be broadly divided into 2 main groups: Primary constipation and secondary constipation. 14

Normal transit constipation: also known as functional constipation is the most common in which although the stool passes through colon at a normal rate, patients find it difficult to evacuate their bowels. The common causes include bad dietary habits, stool withholding habits, lack of fluid intake and lack of physical activity, etc. Slow transit constipation: There is prolonged delay in passage of stool through the colon with complaints of abdominal bloating and infrequent bowel movements. Although the causes remain unclear, abnormalities of myenteric plexus, defective cholinergic innervations, etc. are postulated causes. Anorectal dysfunction: The inefficient coordination of the pelvic musculature in the evacuation mechanism may lead to a feeling of incomplete evacuation, a sense of obstruction, or a need for digital manipulation. It may be an acquired behavioral disorder, or the process of defecation may not have been learned in childhood . 7

In secondary constipation, a medical condition or medication is the cause of constipation and eliminating the particular medication or treating the underlying medical condition may relieve the constipation. The potential causes of secondary constipation include: Endocrine and Metabolic diseases like Diabetes mellitus, Hypercalcemia, Hyperparathyroidism, Hypothyroidism, Uremia, Cushing syndrome; Myopathic conditions like Amyloidosis, Myotonic dystrophy, Scleroderma; Neurologic diseases like Autonomic neuropathy, Cerebrovascular disease, Hirschsprung’s disease, Multiple sclerosis, Parkinson’s disease, Spinal cord injury, tumors; Structural abnormalities like Anal fissures, strictures, hemorrhoids, Colonic strictures, Inflammatory bowel disease, Obstructive colonic mass lesions, Rectal prolapse or rectocele; Psychological conditions like Anxiety, Depression, Somatization; Medications like Opioids, antidepressants, antacids, calcium channel blockers, iron, anticholinergics, psychotropics; and in other conditions like pregnancy and irritable bowel syndrome . 7

Risk factors: Some of the common risk factors for constipation are inadequate diet (fluid or fiber), age >55 years, pregnancy, limited mobility, medications (polypharmacy) especially in the elderly, depression, low income and lower education level, physical and sexual abuse, female gender (higher reporting), recent abdominal or perianal/pelvic surgery, laxative abuse, travel and terminal care patients. Treatment: The cleansing therapy of alimentary canal as mentioned in Ayurveda has many formulae/ herbs used as laxatives, which were described more than 5000 years ago. “Feeling irregular” might have been a common question in ancient Egypt, since laxatives appear to have

dominated their medicinal use, with bulk laxatives such as figs, bran and dates in common use. Since then we have come a long way in use of different laxatives according to their mode of action. There is however some degree of overlap between different groups and in some cases the exact mechanisms of action are not known clearly. Many traditionally used laxatives have fallen from use, owing to the violence of their action or their adverse effect profile. Of late, osmotic laxatives are widely used throughout all age groups commonly for their precise and effective action. Osmotic laxatives act by increasing intestinal osmotic pressure thereby promoting fluid retention within the bowel. The drugs used under this class are magnesium and sodium salts, glycerol, lactulose and lactitol. Lactulose (β -galactosido-fructose) has been used since 1966 for hepatic encephalopathy and is now widely accepted and used as the drug of choice for treatment of constipation. It is a synthetic non-digestible sugar disaccharide containing b-galactose and fructose. 8

Lactitol (β -galactosido-sorbitol), a disaccharide analogue of lactulose has also been described and used as a laxative . This compound is easily produced from lactose in a chemically pure form and can be dispensed as both powder and syrup form. It is similar to lactulose in that it is neither broken down nor absorbed in the small intestine, but is extensively metabolized by colonic bacteria. It would seem the ideal replacement to lactulose for treatment of both constipation and hepatic encephalopathy due to its better safety profile and patients acceptability. 9

Aim of the study : To evaluate the clinical efficacy and safety profile of lactitol monohydrate versus reference laxative (lactulose) in the treatment of constipation. Study design : This was an open label, parallel design and active comparative post marketing surveillance study. MATERIALS AND METHODS

Study population: The study was conducted amongst 90 patients aged 18 years and above attending 9 clinics (3 in Chennai and 6 in Bangalore) with a history of constipation. The concerned doctor in each clinic enrolled 5 patients in lactitol (Exitol) group and 5 patients in lactulose group randomly. Inclusion criteria: Men and non-pregnant women above 18 years of age fulfilling the Rome III diagnostic criteria for functional constipation were included in the study. Exclusion criteria: Patients on drugs like opioids, antidepressants, antacids, calcium channel blockers, iron, anticholinergics, psychotropics, etc. were excluded from the study. Also patients with secondary constipation as mentioned above were excluded from the study. Patients with severe renal or hepatic insufficiency, pregnant or lactating women and patients with cardiac conditions were also excluded from the study.

EVALUATION OF CLINICAL EFFICACY AND SAFETY OF LACTITOL — KUMAR M ET AL

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

Study procedure: 45 patients with a history of constipation were enrolled in either the lactitol or lactulose group. After detailed history and clinical examination, patients were enrolled in either of the study groups after fulfilling the above study criteria. Each patient was given a free sample bottle of either lactitol (Exitol) or lactulose with instructions on dosage and duration. All patients were advised to consume 15 ml/day orally as a single dose for first three days, and an increased dose of 30 ml per day orally as a single dose for next four days. The dose was to be taken after night meal or just before going to bed for seven consecutive days. Follow-up and assessment: All patients in both the study groups were instructed to attend the clinic on day 4 and on day 8 for clinical evaluation. At these follow-up visits, the patients’ responses to the study drug were recorded in a structured form for both the study groups. They were enquired about the Spontaneous Bowel Movement (SBM) count or number of stools passed, SBM (stools passed) within 24 hours and 48 hours of first drug administration, frequency of enemas, suppository used or digital evacuations in seven days of treatment. Patients self assessed the taste and palatability of the drug as satisfactory, average or unsatisfactory. They were also enquired for subjective symptomatic relief (pain and straining during defecation, belching/flatulence, feeling of fullness in stomach, consistency of stools, abdominal distention and sensation of incomplete evacuation). The overall patient’s response to the drug was assessed as satisfactory, average or unsatisfactory. Study end points: Primary end point was the proportion of patients with SBM count of 3 or more at the end of 7 days known as complete response to treatment without using any other laxatives during this period. The secondary end point was proportion of patients with a SBM within 24 hours and 48 hours of first drug administration and the drug’s safety profile. Safety and tolerability assessment were carried out throughout 7 days of study period. OBSERVATIONS

in lactitol group versus 7.2 in lactulose group. Proportion of patients with their first SBM after first drug administration within 24 hours was 73% in lactitol group versus 53.33% of patients in lactulose group and within 48 hours was 93% in lactitol group and 84.44% of patients in lactulose group. Though the frequency of evacuations were more in lactitol group compared to lactulose group, we found that there was no significant difference (p = 0.1079) in terms of bowel movement produced by lactitol (9.302 ± 1.090) or lactulose (7.209 ± 0.6857). Consistency of stools: Normal/soft consistency stools were seen in 75.28% patients of lactitol group compared to 67.05% in lactulose group. Palatability of the drug: Taste and the palatability of drug were found satisfactory by 80.90% of patients in lactitol group compared to 48.86% in lactulose group. A significant proportion of patients treated with lactitol found it to be more palatable and had better patient compliance as compared to patients treated with lactulose. Overall patient’s acceptability: The overall patient’s response was satisfactory for 80.90% of patients in lactitol group and 47.73% in lactulose group. Incidence of adverse events: There were 3 cases of major adverse reactions though not serious in nature, two in lactulose group and one in lactitol group. In lactulose group, one patient had severe abdominal pain with weakness and the other had severe dehydration with weakness. Both these patients stopped treatment after three days of taking medication. In lactitol group, one patient stopped medication by third day due to watery stools. There were higher frequency of minor adverse effects like pain and straining on defecation, nausea and vomiting sensation due to excessive sweetness, sensation of incomplete evacuation and flatulence in lactulose group compared to lactitol group. Lactitol was found to be significantly superior to lactulose in terms of less number of adverse reactions (p=0.0309) i.e., 27.16 ± 3.923 % versus 42.93 ± 5.122 % (Table 1). DISCUSSION

Constipation has become a common problem, both in hospitalized and community dwelling population. Though the definition of normal bowel function varies, it has been suggested that normal defecation frequency is between three times a days to three times per week .

Analysis and Results: Statistical analysis was carried out with help of Graph pad prism (version 5) software to find out significant differences between the two laxatives. We analyzed the study data for Spontaneous Bowel Movement (efficacy) and incidence of adverse Table 1 — Summary of Results events (safety profile in both the study groups) using unpaired t-test with 95% confidence interval. Parameters Lactitol Spontaneous Bowel Movement: The Spontaneous Bowel Movement/week 9.302 ± 1.090 proportion of patients having a SBM count of 3 or Incidence of side effects 27.16 ± 3.923% more at the end of 7 days having a complete response Consistency of stools (normal/soft) 75.28% Satisfactory taste and palatability of drug 80.90% to treatment was found to be equal in both the study Overall patient’s acceptability of drug 80.90% groups (93%). The average SBM per week was 9.3 10

In this current post marketing surveillance study, lactitol and lactulose were administered to 45 patients each with history of constipation based on inclusion and exclusion criteria. Lactitol was found to be at par with lactulose in terms of SBM (9.302 ± 1.090 versus 7.209 ± 0.6857, p=0.1079). Normal/Soft consistency stools were seen in 75.28% patients of lactitol group compared to 67.05% in lactulose group in our study. As per Hammer and Ravelli study 76% of patients with lactitol reported normal or soft stools compared to 67 % patients with lactulose and similarly in Doffoel et al study it was 85% and 83% with lactitol and lactulose respectively. Our results were found to be comparable with the previous comparative studies of lactitol and lactulose with respect to normal/soft consistency of stools. Lactitol was found to be significantly superior to lactulose in terms of less number of adverse reactions (27.16 ± 3.923 % versus 42.93 ± 5.122 %, p=0.0309) in this study. In the Hammer and Ravelli comparative trial, adverse events were observed in 32% patients treated with lactitol compared to 61% patients with lactulose (p=0.02) and similarly a meta analysis conducted by Amit Maydeo in constipation had reported incidence of adverse reaction of 31.20± 0.800 versus 62.10 ± 1.100%, p=0.0019 with lactitol and lactulose respectively. The significant difference in adverse reaction profile between lactitol and lactulose seen in our study are similar to published literature (p<0.05). Taste and the palatability of drug were found satisfactory by 80.90% of patients in lactitol group compared to 48.86% in lactulose group. Our study results were found to be similar to the previous study by Pitzalis et al , where patients treated with lactitol found it to be more palatable and had better compliance compared to lactulose. A study by Lanthier et al had stated that the reasons for greater acceptability of lactitol over lactulose were its more predictable cathartic effect, convenient once a day dose formulation and preference of its less sweet taste. The overall patient’s response was satisfactory for 80.90% of patients in lactitol group and 47.73% in lactulose group. This was comparable to the study by Sacchetta et al with an overall patient’s acceptability of 73 % in lactitol group and 26.8 % in lactulose group. A meta-analysis study by Amit Maydeo shows patients acceptability for lactitol was 73.2 % compared to 26.8% in lactulose group. The low acceptance of lactulose could be due to its excessive sweetness leading to nausea and gastro-intestinal side effects like meteorism and flatulence . Several clinical trials have shown that lactitol consumption does not increase blood glucose or insulin levels. The FDA allows the use of a self determined value of 2 kcal/g for lactitol. As sugars normally have 4 kcal/g, the net energy contribution of lactitol is therefore only 50%. This could be advantageous for treating constipation in diabetic patients. Based on the above facts 11

Lactulose 7.209 ± 0.6857 42.93 ± 5.122% 67.05% 48.86% 47.73%

and studies lactitol could be the ideal successor to lactulose in treatment of constipation. Conclusion: In view of the current post marketing surveillance study and review of previous literature, we recommend lactitol to be the ideal drug in the treatment of constipation, as lactitol offers efficacy comparable to lactulose with lesser adverse effects and patient’s satisfaction superior to lactulose. Acknowledgement: We thank Padma Shri Dr. Ahmed Ali (Consultant Gastroenterologist, Chennai) for his support and advice for the study, the patients who took part in the study with their valuable feedback, Mr. Abhay Kanoria (CMD – AFDIL), Mr. Partha Mukherjee (VP sales-AFDIL) & Mr. Ravi Kumar (SM, South-AFDIL) for logistics support and Ms. Shobhita Jayarama (AFDIL) for helping in preparation of this manuscript. REFERENCES 1 National Digestive Diseases Information Clearinghouse, National Institute of Health – Constipation: Fact Sheet. http://digestive.niddk.nih.gov/ddiseases/pubs/constipation / (accessed on June 28, 2011). 2 Chang L — Irritable bowel syndrome and functional constipation: scope of the problem. Adv Stud Med 2005; 5: S947-954. 3 World Gastroenterology Organization Global guideline: Constipation - A global perspective. Journal of Clinical Gastroenterology 2011; 45: 483-7. 4 Constipation, Myths, Misconceptions and methods to overcome it. www.healthjockey.com (Accessed on June 28, 2011). 5 Tytgat GN, Heading RC, Muller-Lissner S, Kamm MA, Scholmerich J, Berstad A et al — Contemporary understanding and management of reflux constipation in the general population and pregnancy: a consensus meeting. Aliment Pharmacol Ther 2003; 18: 291-301. 6 Rome III Diagnostic Criteria for functional gastrointestinal disorders, Rome Foundation - Appendix A. http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_8 85-898.pdf (accessed on June 29, 2011). 7 Hsieh C — Treatment of constipation in older adults. Am Fam Physician. 2005; 72: 2277-84. 8 Lanthier PL, Morgan MY — Lactitol in the treatment of chronic hepatic Encephalopathy: an open comparison with lactulose. Gut 1985; 26: 415-420. 9 Patil DH, Westaby D, Mahida YR, Palmer KR, Rees R, Clark ML et al — Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy. Gut 1987; 28: 255-9. 10 Drossman DA, Zhiming L, Andruzzi E, Temple RD, Talley NJ, Thompson G et al — U.S. Householder survey of functional gastrointestinal disorders Prevalence, sociodemography and health impact. Dig Dis Sci 1993; 38: 1569-80. 11 Maydeo A — Lactitol or lactulose in the treatment of chronic constipation: result of a systematic. J Indian Med Assoc 2010; 108: 789-92. 12 Pitzalis G, Deganello F, Mariani P, Chiarini-Testa MB, Virgilii F, Gasparri R, et al — Lactitol in chronic idiopathic constipation in children [Eng Abstr]. Pediatr Med Chir 1995; 17: 223-6. 13 Riggio MD, Balducci D, Ariosto F, Merli M, Pieche U, Pinto G et al — Lactitol in prevention of recurrent episodes of hepatic encephalopathy in cirrhotic patients with portalsystemic shunt. Digestive Diseases and Sciences 1989, 34: 823-9. 14 Mesters P — Lactitol, Bulk sweetener for sugar free and reduced calories hard candy. The Manufacturing Confectioner 1995; 61.

Practitioners' Series

TO STUDY THE STATUS OF FREE RADICALS AND OXIDATIVE STRESS — SINGH AND TIWARI

To study the status of free radicals and oxidative stress (superoxide dismutase activity) and the role of antioxidants (tocopherol and ascorbic acid) in the patients of Epilepsy 1

Chandrapal Singh , Paritosh Tiwari

The level of MDA a formed product in oxidative reaction and SOD an enzyme that participates in oxidative reactions help in scavenging the free radicals. The level of MDA is higher and SOD is lower than normal in epileptic cases but therapy with antioxidants (Tocopherol and Ascorbic acid) decreases levels of MDA and increases levels of SOD in epileptic cases after completion of 12-14 weeks therapy along with reduced seizure frequency. [J Indian Med Assoc 2016; 114: 18-22]

Key words : Tocopherol, ascorbic acid, MDA, SOD, TBARS, free radicals.

ree Radicals are defined as molecular species capable of independent existence and contain one or more unpaired electrons in their outermost orbit. Such molecules are highly reactive and produced in our body due to various oxidative processes.

(2) To study the role of antioxidants (tocopherol and ascorbic acid) in the patients of Epilepsy. MATERIALS AND METHODS

The material for present study comprised of cases of different types of epilepsy, admitted in Department of Medicine or Medical Out door of NIMS Medical College and Hospital, Jaipur. Each case of epilepsy was subjected to detailed clinical history from patients or from the attendants of the patient who were witness to the seizure. For each patient the information was collected on several variables of known or suspected contributor. It included age, sex, age at the onset of seizures, frequency of seizures, seizures type, aetiological factor, precipitating factors. Routine investigation carried out in each case included blood for Hb, TLC, DLC, ESR; Urine for routine and microscopic examination for sugar, albumin and casts; Mantoux Test was done when needed; Liver function tests- Serum bilirubin, SGOT, SGPT, Prothrombin Time; Kidney function test- Blood Urea, Serum creatinine, Serum Na /K ; Blood sugar Fasting, Post-Prandinal; Chest X-Ray-PA and lateral views. EEG (Electroencephalogram), CT scan head and /or MRI brain was carried out in as many cases as possible for the classification of epileptic cases

The nervous system is especially vulnerable to the damaging effects of highly reactive Free Radicals for a number of reasons. The brain contains high amount of polyunsaturated fatty acids that are susceptible to lipid per-oxidation, receive a large percentage of oxygen and is relatively deficient in certain anti-oxidant enzymes. Researchers have evaluated the role of oxidative stress in epilepsy in several animal models and its correlation in human beings. Several antioxidants have also been studied, especially Vitamin E and Vitamin C, and a beneficial effect with respect to epilepsy was shown. As per the studies, vitamin E and vitamin C are thought to have a possible role in delaying/preventing the neurodegenerative effects of oxidative stress. However, clinical guidelines for their use mandate a thorough evaluation of the cause and effect relationship for universal acceptance.

Aims and Objectives : (1) To study the status of free redicals and oxidative stress (superoxide dismutase activity) in epileptic cases

Study Cases : Cases were divided into two study groups: Group-I : Epileptic cases Group-II : Control Group

Department of Medicine, NIMS Medical College and Hospital, Jaipur 303001 1 MBBS, MD (Med), Assistant Professor 2 MBBS, Resident 18

Inclusion Criteria : (1) Age between 15 to 60 years, ensuring a representative sample of epileptics, comparable with the standardization samples of the questionnaire used. (2) Epilepsy corroborated on the basis of clinical history and /or abnormal E.E.G. (3) A minimum period of epilepsy with one year, during which five or more epileptic attacks had occurred. (4) Both new and follow up patients of epilepsy were taken for the study. (5) No clinical evidence of drug overdose and postictal effects at the time of assessment.

Exclusion Criteria (1) Patients beyond the age group i.e. more than 60 years and less than 15 years. (2) Patients’ suffering from organic brain syndrome due to causes other then epilepsy. Special care was taken to exclude patients with a progressive cerebral disorder. (3) Any other co-morbid condition like hypertension, stroke, diabetes mellitus , superadded infections etc. which can lead to oxidative stress.

Estimation of Free Radicals : Direct detection of super-oxide and hydroxyl radicals with in biological system is very difficult primarily because of their low concentrations (10-11 m) and their extremely short life span (only a few milliseconds). Three principal approaches are currently used to ascertain whether oxidative stress has occurred. The first of these is to use exogenous spin traps for free radical species and then analyze for the trapped species by electron spin resonance. Another approach is to analyze biological materials for products of reactive oxygen species (shiff bases), lipids (lipid per- oxidation markers, fatty acid profiles) and nucleic acids (8-hydroxy guanine). Thirdly, it may be possible to determine whether there is depletion of anti-oxidant status).

Collection of Blood for Bio-chemical Analysis : After obtaining informed consent from the patients and controls of the study groups, blood sample were taken at the time of inclusion of patient for the study. Blood (10 ml) was withdrawn from the anticubital vein using disposable plastic syringes fitted with twenty gauge needle and transferred in to plastic tubes containing 3.89% tri-sodium citrate in the ratio of 9:1. The contents in the tube were mixed gently and processed for the biochemical examination.

Preparation of Platelet Rich Plasma and Isolation of Platelets : Blood was centrifuged at 200 xg for 10 minutes and the supernatant containing platelet rich plasma (PRP) was aspirated out into another plastic tubes. The PRP was centrifuged at ISOOxg for 20 minute at 4 C to sediment the platelets. The platelets were washed with platelet buffer (PH 6.5) and finally re-suspended in 0.1 M phosphate buffer saline (PH 7.4) and then it was used for the determination of lipid per-oxidation products and activities of super-oxide dismutase (SOD). 0

Bio-chemical Analysis : (A) Assay of lipid per-oxidation products as a marker of oxidative stress: malonal dialdehyde (MDA): As a measure of lipid per oxidation malonaldialdehyde formation (MDA) was estimated using the level of thio-barbituric acid reactive substances (TBARS) according to the method of Bohme et al, 1997 . This is one of the most commonly applied assays to, measure malonaldialdehyde (MDA) as a maker of lipid per-oxidation products. Procedure — Equal volumes 120 µl Of EDTA (10m M) ascorbate (10m M) and mixture of EDTA (16.7m M) and FeSO4 (16.7 m M) were mixed. Then platelet suspension (840 µl) was added in this mixture. In starting, mixture was incubated at 37 C for O and 90 minutes. The reaction was stopped by adding 1ml of ice-cold 10% trichloroacetic acid (TCA). The mixture was centrifuged at 200 xg for 10 minutes and supernatant was aspirated out. Deproteinised homogenates were centrifuged at 200 xg for 10 minutes and supernatant was aspirated out. Supernatant (2 ml) was fixed with equal amount of 0.67% TEA and kept in boiling water bath 15-20 minutes. The intensity of pink color developed was read at 532 nm on a spectrophotometer. MDA is read as n. moles MDA formed/hr/108 platelets. (B) Assay of super-oxide dismutase activity : The assay of super-oxide dismutase (SOD) activity was carried out following the method of Kakkar et al. (1984) with minor modification . The assay mixture in a final volume of 3 ml contain sodium pyrophosphate buffer (0.082 M., PH 8.3), phenazonium methosulphate (18>n/1), nitroblue tetrazolium (300 nM), NADH (780uM), diluted enzyme preparation and distilled water. The reaction was initiated by addition of NADH, followed by incubation at 37 C for 90 seconds. The reaction was stopped by adding 1 ml in butanol. The mixture was allowed to stand for 10 minutes, centrifuged and butanol layer was separated. The color intensity of the chromogen in butanol layer was measured at 560 nm against butanol over a spectrophotometer. A mixture without enzyme preparation was run in parallel to 1

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

serve as control. The SOD activity was expressed unit/minute/108 platelets. One unit of the enzyme was the amount required to inhibit the rate of chromogen formation by 50%. Patients and controls were given 400 mg of vitamin E and 500 mg of vitamin C for a period of 12-14 weeks. Values of superoxide dismutase (SOD) and Malonaldialdehyde (MDA) were measured prior to giving vita E and C and values were again checked after completion of 12-14 weeks of therapy and the two values were then compared with each other.

TO STUDY THE STATUS OF FREE RADICALS AND OXIDATIVE STRESS — SINGH AND TIWARI Table 1 — Average Levels of MDA in Platelets of Epileptic Groups of Patients and Control Group according to Sex Groups

Epileptic Group Control Group Groups

Male

Sex

Female

OBSERVATIONS

A total of 135 patients were included in the study. They were divided into two groups. The numbers of patients in each group were as follows: Group-I : Epileptic cases n= 85 (62.96%) Group-II : Control group n=50 (37.04%) The total cases included in the study were 135 out of which 88 (65%) were males and 47 (35%) were females. Total epileptic cases were 85 in which 59 (69.41%) were male and 26 (30.59%) were female. In control group 50cases were out of which 29 (58%) were male and 21 (42%) were female. The mean age of epileptic cases was 30.00 ± 10.38 year, in group II was 23.42 ± 11.27. The age of onset of epilepsy in 4 (4.71%) patients was less than 10 years, 23 (27.06%) patients belonged to the group with 11-20 years, 39 (45.88%) patients belonged to the group of 21 to 30 years, and 14 (16.47%) patients belong to the age group of 31 to 40 years and 5 (5.88%) patients in group of 41 to 50 years. Mean age of onset of seizure in group was 23.19 ± 8.09 years. The group of distribution of patients according to duration of epilepsy is less than 5years in 34 cases, 5 to10years in 32cases, 10 to15years in15 cases, and 21 to25years in 4 cases. The mean duration of epilepsy was 6.39 ± 5.14 years. The numbers of episodes of seizures less than 20 in 41 cases, 21 to 40 in 18 cases, 41 to 60 in 8 cases, 61 to 80 in 13 cases, 81 to 100 in 3 cases and more than 100 in 2 case. The mean number of episode was 34.99±28.10. Levels of MDA were significantly raised and that of SOD were significantly decreased in all types of epilepsy without any significant statistical difference amongst different types of seizure activities. Table 1 shows average value of MDA in the patients in different groups of patients according to their sex and if we compare average value of MDA of epileptic patient (includes all types of seizure activities) with control group the average values of MDA significantly differ from control group and these data were statistically significant i.e., p< 0.001.

Table 3 — Average Levels of MDA in Platelets of Epileptic Group and Control Group of Patients according to Sex after Tocopherol and Ascorbic Acid (Vitamin E and C) Therapy

Total

No. Mean SD T P

59 2.33 0.3 30.769 < 0.001

29 0.5 0.16

No. Mean SD T P

23 2.32 0.22 35.293 < 0.001

21 0.46 0.111

No. Mean SD T P

85 2.32 0.27 44.477 < 0.001

50 0.484 0.145

Sex

Table 2 shows the average level of SOD in platelets in epileptic group (includes all types of seizure activities) of patients and control group according to their sex. The difference of average values of epileptic group was statistically significant (p<0.001) from the control group.

Table 2 — Average Levels of SOD (Superoxide Dismutase) in Platelets Epileptic Group and Control Group of Patient according to Sex Groups

Male

Sex

Female

Total

Group I

Control

No. Mean SD T P

59 3.4 0.42 11.878 < 0.001

29 4.41 0.23 -

No. Mean SD T P

26 3.39 0.49 8.377 < 0.001

21 4.37 0.24

No. Mean SD T P

85 3.4 0.42 15.367 < 0.001

50 4.398 0.236

Control

Male

No. Mean SD T P

59 1.83 0.3 30.769 < 0.001

29 0.5 0.16 -

Female

No. Mean SD T P

26 1.82 0.22 35.293 < 0.001

21 0.46 0.111

Total

No. Mean SD T P

85 1.82 0.27 44.477 < 0.001

50 0.484 0.145

Table 4 — Average Levels of SOD (Superoxide Dismutase) in Platelets of Epileptic group and Control Group of Patient according to Sex after Tocopherol and Ascorbic Acid (Vitamin E and C) Therapy Groups

Table 3 shows average value of MDA in the patients in different groups of patients according to their sex, it has been observed that after giving the tocopherol and ascorbic acid (12-14 weeks) the level of MDA was decreased in comparison to the data in Table 1. The Table 4 shows that average values of SOD were significantly higher in epilepsy patient in comparison with previous data in table 2 after tocopherol and ascorbic acid (12-14 week, Vitamin E and Vitamin C Therapy), these data are found statistically significant (p<0.001).

Group I

Sex

Group I

Control

Male

No. Mean SD T P

59 3.9 0.42 11.878 < 0.001

29 4.41 0.23 -

Female

No. Mean SD T P

26 3.89 0.49 8.377 < 0.001

21 4.37 0.24

Total

No. Mean SD T P

85 3.5 0.42 15.367 < 0.001

50 4.398 0.236

DISCUSSION

Nervous system is especially vulnerable to the damaging effects of highly reactive free radicals for a number of reasons. The brain contains high amount of polyunsaturated fatty acid that are susceptible to lipid peroxidation, receives a large percentage of oxygen and is relatively deficient in certain antioxidant enzymes and hence antioxidant defenses are critically important to protect the brain. Brain has an antioxidant, defense mechanism. The brain micro vessels, which constitute the blood brain barrier, protect the brain from various toxic injuries

including oxidative damage. The majority of available research on the role of antioxidant nutrient in neurological functions and disease has focused on Tocopherol and Ascorbic Acid (Vitamin E and Vitamin C), which are major antioxidants. In the body, they protect the integrity of membranes by inhibiting lipid per-oxidation. It is known that oxidative stress occurs in patients of epilepsy and present study was conducted to find if there is any change of oxidative stress in patients of epilepsy and role of antioxidants (Tocopherol and Ascorbic Acid). To study these we measured the level of MDA (malonedialdehyde), a formed product in oxidative reactions and SOD (superoxide dismutase) an enzyme that participates in the oxidative reactions that help in scavenging the free radicals, thus preventing the damaging effect of these free radicals. The study of oxidative stress was done in 85 epileptic patients and 50 patients were controls. The mean MDA levels in cases of epilepsy were 2.41 ± 0.2 and in controls 0.484 ± 0.145. Similarly the level of SOD was measured in the above mentioned groups. The level of SOD in epileptic cases was 3.40 ± 0.42 and in controls 4.398 ± 0.236. The mean MDA levels were 1.82 ± 0.27 in cases of epilepsy and in controls 0.484 ± 0.145. The mean MDA level was significantly decreased after tocopherol and ascorbic acid therapy in patients of epilepsy. Similarly the level of SOD was measured in the above mentioned groups. The level of SOD in epileptic Group was 3.90 ± 0.42 and in controls was 4.398 ± 0.236. It was found that mean levels of SOD were higher in epileptic cases after tocopherol and ascorbic acid therapy in comparison to without tocopherol and ascorbic acid therapy and these data are found statistically significant ie, p < 0.001. This observation is substantiated by studies showing a very important role of oxidative stress in epilepsy. Sudha, Rao and Rao (2001) showed the role of oxidative stress in their study on 29 epileptic patients, by demonstrating a decrease in various antioxidant defenses and an increase in oxidative stress parameters . Rokyta, Racek and Holecek (1996) reiterated the role of free radicals in epilepsy and the benefit of antioxidants in them . Ramackers et al (1994) in their study demonstrated increased oxidative stress in epilepsy and showed improvement with antioxidant in the form of selenium supplementation . Weber et al (1991) demonstrated glutathione peroxidase deficiency in childhood seizures and improvement in clinical state after discontinuation of anticonvulsant medication and selenium substitution . Kryzhanovski et al (1984) showed in a study of 43 patients that lipid per-oxidation products and free 3

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

fatty acids in both CSF and plasma were significantly higher in epileptic patients thus proving the role of oxidative stress in epilepsy . Similar, studies of oxidative stress in epilepsy in animal models further substantiate the results. Lores et al (1998) demonstrated that increase in oxidant species and not depletion of antioxidant defenses is responsible for the actual oxidative stress during epilepsy . Ueda et al (1998) supported the note of oxidative stress in epilepsy in his work . Singh and Pathak (1990) in their work by induction of epilepsy of FeCI demonstrated an increase in peroxidation product especially on the side of epileptogenic foci coupled with a decrease in glutathione peroxidase level . The mean age of epileptic cases was 30.00 ± 10.38 years and control group was 23.42 ± 11.27 years. The age onset of epilepsy in epileptic cases patients was 23.19 ± 8.09 years. The average duration of epilepsy was 6.39 ± 5.14 years in epileptic cases which is comparable to the other studies. The mean level of MDA was lower after tocopherol and ascorbic acid (Vitamin E and Vitamin C) therapy in epilepsy and in comparison with control the difference was statistically significant (p< 0.001). In this study the average level of SOD was higher after tocopherol and ascorbic acid (Vitamin E and Vitamin C) therapy in patients of epilepsy compared to control the difference was statistically significant (p<0.001). Epileptic patients had higher level of SOD and lower level of MDA in the platelets in comparison to previous data after tocopherol and ascorbic acid therapy. The study demonstrates that abnormalities in MDA and SOD occur in patients with epilepsy. Whether these changes indicate a generalized metabolic disturbance that contributes to the pre-disposition of epilepsy remains to be proved. All patients were given Tocopherol and Ascorbic acid for minimum of 12 to 14 weeks along with optimum antiepileptic therapy. Patients were followed for one and half year duration only. There was slight decrease in the seizure frequency but as we also continued optimum antiepileptic therapy, it is difficult to determine whether the decrease in seizure frequency is because of anti oxidants or antiepileptic drug therapy. We also have not decreased the doses of antiepileptics. This requires long term follow up study including large no. of patients. 7

REFERENCES 1 Karlsson J — Introduction to Nutraology and Radical Formation. In: Antioxidants and Exercise. Illinois: Human Kinetics Press, 1997, p 1-143. 2 Kakkar P, Das B, Vishwanathan PW — A modifies spectrohotometric assay of Superoxide dismutase. Indian J Biochem Biopsys 1984; 21: 130-2. 3 Sudha K, Rao AV, Rao A — Oxidative stress and antioxidants in epilepsy. Clin ChjRf Ada 2001; 303: 15-24, 51. 4 Rokyta R , Racek J , Holecek v : Free radicals in the central nervous system Cesk Fysiol 1996; 451:4-12. 5 Ramackers VT, Calomme M, Vanden Bergh D — Selenium

deficiency triggering intractable seizures. Neuropediatrics 1994; 25: 217-23. Weber GF, Maertens P, Meng XZ — Glutathione peroxidase deficiency and childhood seizures. Lancet 1991; 337: 14434. Kryhanovski GN, Nikushkin EV, Voronko VA, Kovalenko VM, Pronina IG — Concentration of lipid peroxidation products and free fatty acids in the plasma and cerebrospinal fluid of epileptics. Zhural Neuropatologii I Psikhiatrii Imeni SS- Korsakova 1984; 84: 806-9. Lores Amaiz S, Travackr M, LIsuy S, Rodriguez de Lorez Amaiz G — Regional vulnerability to oxidative stress in a model of experimental epilepsy. Neurochem Res 1998; 23: 1477- 83. Ueda Y, Yokoyama H, Ohya-Nishiguchi H, Kamada H — ESR spectroscopy for analysis of hippocampal elimination of a nitroxide radical during kainic acid-induced seizures in rats. Magn Reson Med 1998; 40: 491-3. Singh R, Pathak DN — Upid peroxidation and glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and glucose 6 phosphate dehydrogenase activities in FeCI3-induced epileptogenic fod in rat brain. Epilepsia 1990; 3: 15-26.

Our Respectful Homage To Mohandas Karamchand Gandhi

GP Forum Prevalence of hypertension in children in a rural population of North India — a population based study 1

Most of the hypertensive children are asymptomatic and we do not normally examine their blood pressure, and so hypertension goes undetected, hence the purpose of the study. Two hundred and seventeen children above the age of 6 years in a village were examined in a population based survey. Blood pressure was recorded in all. Mean age was 11.26±3.39 years. One hundred and twelve were male (51.6%) and 105 were females (48.4%), 50 were found to be hypertensive (23.1%), out of which 26 were male and 24 were females. Mean age was 12.11±3.75 years, 20 had high normal blood pressure (9.5%). Family history of hypertension was present in 32(64%) hypertensive children. Prevalence of hypertension was high in children. Majority of hypertensive children had family history of hypertension. [J Indian Med Assoc 2016; 114: 23-4 & 28]

Key words : Blood Pressure, Hypertension, Prevalence.

ypertension (HT) is a major public health problem world wide and is major risk factor for coronary artery disease and cerebro-vascular disease . By the time HT is detected in adults, end organ damage might have started. It has been suggested that adult HT may start early in childhood .There are many studies of HT in children but very few community based studies.

(BP) was recorded in all children. All efforts were made to eliminate the factors which might affect the BP, like anxiety, fear, stress, crying, laughing and recent activity. The children were explained that no painful procedure will be done during the examination. The BP was measured by standardized method according to Task Force recommendation using the mercury sphygmomanometer. Resting BP was determined by auscultation in right upper limb after 10 min. of resting period, in sitting position with exposed stretched arm resting on the table, using appropriate cuff size for age . Kortkaff sounds 1 and 5 were used to determine systolic and diastolic BP respectively. HT and pre HT were defined as per revised norms of fourth report on diagnosis, evaluation and treatment of high BP in children and adoledcents . If a child was found to have high BP, his BP was again recorded after minimum of 5 min. If the BP was still high, only then was the child labeled to have HT. BP of parents of the hypertensive child was also recorded. If any of the parents was hypertensive or there was family history of HT, the child was labeled to have family history of HT. The clinical examination of child was also done to find out any secondary cause for HT.

1-3

MATERIAL AND METHODS

This population based study was conducted in a village “Kunihar” in Solan District oh Himachal Pradesh (HP), which is around 40 km from the state head quarter, Shimla. Village has an affluent population with good per capita income and most of the people are in government job or are businessmen. The study was conducted by seven doctors, including two consultants in Cardiology, two senior residents in Cardiology, two junior residents in internal Medicine and one junior resident in Pediatrics. All children of the village between 6 to 18 years present on the days of study, whose parents volunteered, were examined. The study was conducted on three consecutive holidays, so that most of the children were available. Blood pressure

Born : 2 October 1869 Died : 30 January 1948

Rajeev Bhardwaj , Arvind Kandoria , Rajeev Marwah , Piyush Vaidya , Bakshish Singh , 6 7 Pravesh Dhiman , Avinash Sharma

Results :

Department of Cardiology, Indira Gandhi Medical College, Shimla 171001 1 DM (Cardiol), Professor 2 DM (Cardiol), Assistant Professor 3 MD (Med), Senior Resident 4 MD (Med), Senior resident 5 MD (Med), Junior resident, Department of Medicine 6 MD (Med), Junior resident, Department of Medicine 7 MD (Paediatric), Junior resident, Department of Paediatrics

Two hundred and seventeen children between 6 to 18 years were examined. Mean age was 11.26±years, 112 were males and 105 were females. Fifty of these were found to have HT (23.1%). Twentysix of 112 males had HT (24.07%), where as 24 out of 105 had HT (23.5%). Table 1 shows the prevalence of HT and pre-HT in children. 23

GP Forum

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

Twenty children were found to have pre-HT (9.2%) Table 2 shows the age distribution of children examined, hypertensive and pre hypertensive children. It is seen that the prevalence of HT increases from 17.8% in children below 9 yrs to 33.35 in children between 16 to 18 yrs. 32 children had family history of HT (64%). Since most of the children did not turn up for further investigation, the number of children having secondary HT is not known. DISCUSSION

Information on the prevalence of HT in the community is important, as it a health hazard, is often asymptomatic and patient may come later on with end organ damage. Although the prevalence is lower in children and adolescents than in adults, increasing evidence indicates that essential HT begins to develop during first two decades of life . Our study found a high prevalence of HT and pre-HT in children. The high prevalence could be due to the fact that we just made one screening, and subsequent screening could have found a lower prevalence. In a study, approximately 13% subjects were found to have HT when first examined, but less than 1% had HT when examined again . In a study carried out in USA prevalence of HT in children, when first examined was 10%, where as sustained HT was less than 2% . In another American study, the prevalence of HT after first, 2nd and 3rd screening was 19.4%, 9.5% and 4.5% respectively . In 7

Table 1 — Hypertension, Pre-hypertension and family history of hypertension in children Total children Male Female Mean age (years) Hypertensive Male Female Mean age (years) Pre hypertensive Male Female Family history of HT (hypertensive) Family history of HT (pre-hypertensive)

217 112(51.6%) 105(48.4%) 11.26±3.39 50(23.8%) 26(24.1%) 24(23.5%) 12.11±3.75 20(9.2%) 12(10.1%) 08(7.6%) 32(64%) 12(60%)

Table 2 — Age wise distribution of Hypertension and Prehypertension in children Age (years) Number All 6-8 9-12 13-15 16-18

217 56 86 45 30

Pre HT

Normal

50(23.1%) 10(17.8%) 17(19.7%) 13(28.8%) 10(33.3%)

20(9.2%) 2(3.6%) 11(12.8%) 4(9.1%) 3(10.1%)

147(67.7%) 44(78.6%) 58(7.4%) 28(62.2%) 17(56.1%)

Kuwait, the prevalence of systolic and diastolic HT in children by 18 yrs of age was 12.4% and 7.9% respectively . In an Indian study, 6.6% children were found to have HT on first contact but the prevalence declined to 0.4% in examination after 2 months . Verma et al studied 2560 school children from 5-15 yrs. 2.8% of children had HT on first contact and the prevalence declined to 1.31% when children were re-assessed after 6 months . However, these are all studies of last decades, and prevalence might have increased since then. The present study, though did screen only once and could have overestimated the prevalence of HT, still it also reflects the emerging scenario of epidemic of cardio vascular diseases in recent era . In a similar study in adults in the same village the prevalence of HT was found to be 42.4% (unpublished data), similar to the trend in urban areas, probably due to the nature of population. So the high prevalence in children could also be a reflection of what is seen in adults. An association between family history of HT and HT in children has been found by various workers. In our study, 32 (64%) of hypertensive children had family history of HT(father -15, mother -11, both parents -5 and grand parents-1). Gupta found that 81.3% of children with sustained HT had a family history of HT . Verma et al reported that 85.7% of hypertensive children had a positive family history. In conclusion, the prevalence of HT is high in the community. Since none of the hypertensive children was symptomatic, it underlines the importance of community surveys and school surveys for detection of HT, so that it could be identified and controlled before end organ damage occurs. Since most of the children had a family history of HT, the children with family history of HT require regular screening, being a high risk group. 10

Study of bone mineral density and it’s correlation with serum estradiol level in postmenopausal women 1

Manjari Sinha , Pratiksha Gupta , Pushpa Bhatia , Sudhir K Kapoor

Osteoporotic fractures are a major cause of morbidity and mortality amongst postmenopausal and elderly women. Low bone mass is an important determinant of skeletal fragility and fracture risk. This is due to decreased levels of estrogen /estradiol, produced mainly in the ovaries, leading to reduced bone mineral density (BMD), which is the gold standard for diagnosis of osteoporosis. The purpose of the present study was to determine the relationship between serum estradiol levels and BMD in Indian postmenopausal women. The study, which was of cross-sectional design, involved 53 postmenopausal women meeting the inclusion criteria, viz. healthy postmenopausal women aged 40 years and above having taken no hormonal medications in the previous 3 years. BMD was measured at the lumbar spine, right femoral neck and at the left distal radius by the dual-energy X-ray absorptiometry (DEXA) instrument. The mean serum estradiol concentration was 12.16 ± 8.58 pg/ml, while in 37.74% of the subjects the estradiol concentration was < 5 pg/ml. Serum estradiol level was positively correlated with BMD of Right femoral neck, Lumbar spine and Distal radius as evidence by Karl Pearson coefficient of correlation were 0.792 , 0.670 and 0.594 respectively. The correlation was more stronger in cases with serum estradiol level less than 5pg/ml (Karl Pearson coefficient of correlation 0.821, 0.807 and 0.873 at lumbar spine, right femur and distal radius respectively). Thus the higher the serum estradiol levels, the higher the BMD values. In conclusion, the results of this study point to estradiol levels as a major factor in determining the BMD values in postmenopausal women. [J Indian Med Assoc 2016; 114: 25-8]

Limitations of Study : (1) The BP of hypertensive children was not reassessed after some interval and so the study could have overestimated the prevalence of HT. (2) Weight and height were not recorded. So no record of obesity in the community is available, which itself is a high risk group for HT. Hence a larger study, with follow up at least once children found to be hypertensive is recommended to find the true prevalence of Ht in children. REFERENCES 1 Report of a WHO expert committee. World health Organization. Arterial hypertension. Tech Rep Ser 1978; 628: 7-26. 2 Yamini MH, Massie BM — Hypertension, myocardial ischemia and sudden death. Curr Open Cardiol 1944; 9: 542-50. 3 Petrovitch H, Curb JD, Bloom-Marcus E — Isolated systolic hypertension and risk of stroke in Japanese- American men. Stroke 1995; 26: 25-9. (Continued on page 28)

Key words : Postmenopausal, Estradiol, Bone mineral density, Dual energy X-ray absorptiometry.

enopause is defined as the cessation of menstrua-tion for 12 months in a woman and occurs on an average at the age of 51 years. It represents permanent failure of ovarian function secondary to depletion of the follicular pool. With the increasing longevity there is a concomitant increase in the number of elderly particularly postmenopausal women in developed as well as developing countries. In postmenopausal period, the ovaries are no longer functional leading to decreased level of estradiol . The remaining source of estradiol is the adrenals, adipose tissues and muscle through aromatization of androstenedione . After the age of 30 years, there is gradual diminution of bone mass which is most clearly seen in women who experience significant decreases in bone mass. This is associated with lowered estrogen production several years prior to the onset of menopause . The abrupt decline in serum estradiol levels after menopause contributes to accelerated bone loss4.

Osteoporosis is a condition of diminished bone mass and change in bone architecture upto the fracture threshold without clinical signs or symptoms . In this disorder, the rate of bone formation is frequently normal but the rate of bone absorption is increased. Bone loss occurs more frequently in trabecular bone such as in the vertebrae, femoral neck and distal radius . Estrogen deficiency causes bone loss by two mechanisms , activation of new bone remodeling and exaggeration of imbalance between bone formation and resorption. Bone mineral density is the amount of matter per cubic centimeter of bone. It is used as indirect indicator of osteoporosis and fracture risk. DualEnergy X-ray Absorptiometry (DEXA) scan is used most widely and this test is highly accurate to measure bone mineral density. 5

MATERIALS AND METHODS

Present study is a cross-sectional study. A total of 53 cases were enrolled in study group who fulfilled the inclusion and exclusion criteria from outpatient department and admitted in wards ESIC-PGIMSR, Basaidarapur, New Delhi. Inclusion Criteria are postmenopausal women 40 years and above, actively mobile (Requiring no walking

Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Sciences and research, ESIC, New Delhi 110015 1 Post Graduate Student (MD) 2 MD, Associate Professor 3 MD, Professor & Head 4 MS, Professor & Head of the Department of Orthopaedics 25

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

aids) and willing to participate in study. Exclusion Criteria are women undergone hysterectomy or bilateral Oophrectomy (surgical menopause), acute infection, Diabetes Mellitus, diseases of Kidneyand Liver, malignancies, hormonal therapy in the last 3 years and chemo radiation. After measurement of serum estradiol level and BMD by DEXA scan at lumbar spine, right femoral neck and distal radius, correlations were calculated. Informed consent and thorough history was taken from all subjects and followed by clinical examination. Anthropometric examination and Pap smear examination was done for all patients. Serum estradiol and Follicular stimulating hormone (FSH) levels were measured by ELISA technique on weekly basis. Standard curves were plotted for both the tests using multipoint calibration and values were calculated from the standard curve. Bone Mineral Density of Lumbar Spine, the right femoral neck and distal radius were determined by Dual Energy X-ray Absorptiometry (DEXA) scan using a Dexa lunar prodigy system. In our study WHO guidelines was used for assessment of bone loss. Normal -T Score above -1, Osteopenia -T Score between -1 to -2.5 and Osteoporosis -T Score below -2.5. Statistical analysis- Karl Pearson’s correlation coefficients were calculated. The level of significance was set as p-value less than or equal to 0.05. RESULTS

Out of 53 cases in the study group, total subjects were divided into group A(serum estradiol level <5pg/dl) and group B (serum estradiol level >5pg/dl). A total of 20 cases were enrolled in group A and 33 cases were enrolled in group B. Age wise distribution(yrs) of cases were, 40 to 443.77%(2/53), 45 to 49 -11.32% (6/53), 50 to 54 – 30.19% (16/53), 55 to 59 – 39.62% (21/53) & 60 to 64 - 15.09% (8/53). According to body mass index, cases were underweight-39.62% (21/53), normal- 39.62%(21/53), overweight- 20.75%(11/53) and obese- 0%(0/53). Mean lumbar T-score was –1.96 ± 0.63, mean femoral neck Tscore was –1.59 ± 0.49, and mean distal radial T-score was –1.95 ± 0.62 (Table 1). In this study, the highest prevalence of Osteopenia was for the right femoral neck (92.45%),while the prevalence of osteoporosis was highest in the left distal radius (33.96%) (Table 2). The Karl Pearson Coefficient of correlation showed a positive correlation between serum estradiol and BMD of the Lumbar spine (r=0.670; p<0.001), Right femoral neck (r=0.666; p<0.001) and Distal Radius (r= 0.594; p <0.001) (Table3). Thus the higher the serum estradiol levels,the higher the BMD values for all three region. BMD is more strongly correlated with serum estradiol

GP FORUM Table 1 — Mean values for age, BMI, lumbar, femoral and radial Tscores and estradiol level in postmenopausal women General characteristics

Mean ± SD

Age (years) Body mass index (kg/m2) Underweight Normal Overweight Lumbar T-score Right femoral T-score Left radial T-score Estradiol (pg/dl) < 5.0 > 5.0

54.58± 4.26 20.98 ± 3.94 39.62% 39.62% 20.75% -1.96 ± 0.63 -1.59 ± 0.49 -1.95 ± 0.62 12.16 ± 8.58 37.74% 62.26%

Table 2 — Distribution of Osteopenia and osteoporosis by BMD site in postmenopausal women

Lumbar Spine Right Femoral Neck Distal Radius

Normal

Osteopenia

Osteoporosis

00% 1.89% 00%

75.47% 92.45% 66.04%

24.53% 5.66% 33.96%

level in subjects with serum estradiol level less than 5pg/dl (Table 4). DISCUSSION

Correlation of Lumbar Spine BMD with serum estradiol level : In our study bone mineral density of lumbar spine was significantly correlated with serum estradiol level of study subjects(r =0.670, p<0.001). Women in group A had substantially less BMD at lumbar spine.Cases with serum estradiol level less than 5pg/ml, mean estradiol and mean BMD of lumbar spine were 3.95+/-0.63 and -2.29+/-0.66 respectively. In this group more strong correlation was found (r =0.821, p<0.001). Table 3 — Correlation between serum estradiol and bone mineral density in postmenopausal women

Lumbar Spine Right Femoral Neck Distal Radius

Correlation coefficient

P value

0.670 0.666 0.594

<0.001 <0.001 <0.001

Table 4 — Comparison of Correlation coefficient between serum estradiol and bone mineral density among subject with serum estradiol level <5pg/dl and >5pg/dl in postmenopausal women

Lumbar Spine Right Femoral Neck Distal Radius

r among estradiol <5pg/dl

r among estradiol >5pg/dl

0.821(p<0.001) 0.807(p<0.001) 0.873(p<0.001)

0.792(p<0.001) 0.654(p<0.001) 0.669(p<0.001)

In group B, mean serum estradiol level and mean BMD of lumbar spine were 17.13+/-7.20 and -1.76+/-0.53 respectively. In this group also a strong significant correlation was found (r = 0.792, p<0.001). Additional supportive data were reported by Bagur et al.2004 in postmenopausal women < 65 years of age, who had estradiol levels of > 10 pg/ml and higher BMD values in all skeletal sites examined, in comparison with women whose estradiol levels were < 10 pg/ml . Van Geel et al 2009 in his study involving 370 postmenopausal women aged between 55 and 85 years found a significant positive relationship between serum estradiol levels and BMD values for the lumbar spine (r= 0.201, p<0.001) . In the study by Rogers et al 2002 a positive association was found between estradiol and bone density at all body sites examined (r=0.19, p<0.01) . Zarrabeitia et al 2007 revealed a significant correlation of serum estradiol concentration with BMD of the spine in postmenopausal women. Murphy et al 1992 in his study found a positive correlation between total estradiol and BMD of lumbar spine(Correlation coefficient- 0.30 p < 0.01) . Ettinger et al 1998 found BMD of lumbar spine showed a similar trend to be higher with higher levels of estradiol. Compared to women with serum estradiol levels less than 5 pg/mL, those with levels between 10–25 pg/mL had statistically significant greater mean BMD at lumbar spine; the differences were 7.2% (p<0.05) . Our study hypothesized that bone mineral density of lumbar spine was positively correlated with serum estradiol level. We have extended and validated the findings of Bagur et al 2004 , Van Geel et al 2009 , Rogers et al 2002 , Zarrabeitia et al 2007 , Murphy et al 1992 and Ettinger et al 1998 . Correlation of Right Femoral neck BMD with serum estradiol level : BMD of right femoral neck was significantly correlated with serum estradiol level of study subjects (r = 0.666, p<0.001). Postmenopausal women in group A had substantially less BMD at right femoral neck. In this group, mean estradiol and mean BMD of right femoral neck were 3.95+/-0.63 and —1.90+/-0.48 respectively. In this group more strong correlation was found (r = 0.807, p<0.001). In Group B, mean estradiol and mean BMD of right femoral neck were 17.13+/-7.20 and —1.40+/-0.40 respectively. In this group also strong significant correlation was found (r = 0.654, p<0.001). The results of present study was similar to study done by Mawi 2010 in postmenopausal women aged between 47 and 60 years with the estradiol concentration more than 5 pg/ml, showed a significant positive relationship between estradiol levels and T-scores for the femoral neck region. Van Geel et al 2009 in his study involving 370 8

(10)

(14)

postmenopausal women aged between 55 and 85 years found a significant positive relationship between serum estradiol levels and BMD values for the femoral neck (r= 0.188, r<0.001) . Murphy et al 1992 in his study found a positive correlation between total estradiol and BMD of femoral neck (Correlation coefficient- 0.26 p<0.05) . Ettinger et al 1998 found BMD of total hip showed a similar trend to be higher with higher levels of estradiol . Compared to women with serum estradiol levels less than 5 pg/mL, those with levels between 10–25 pg/mL had statistically significant greater mean BMD at total hip; the differences were 4.6% (p<0.05) . Rogers et al 2002 also found a positive correlation between estradiol and BMD of femoral neck (r=0.20, p<0.01) . Correlation of Distal Radius BMD with serum estradiol level : Bone mineral density of distal radius was significantly correlated with serum estradiol level of study subject (r = 0.594, p<0.001). In group A, mean estradiol and mean BMD of distal radius were 3.95+/-0.63 and -2.22+/-0.61 respectively. In this group more strong correlation was found (r = 0.873, p<0.001). In Group B, mean estradiol and mean BMD of lumbar spine were 17.13+/-7.20 and -1.79+/-0.58 respectively. In this group also strong significant correlation was found (r = 0.669, p<0.001). Ettinger et al 1998 found BMD of proximal radius showed a similar trend to be higher with higher levels of estradiol. Compared with women with serum estradiol levels less than 5 pg/mL, those with levels between 10–25 pg/mL had statistically significantly greater mean BMD at proximal radius; the differences were 5.8% (p<0.05) . Thus the results of our study were similar to the result observed by Bagur et al , Mawi , Van Geel et al , Rogers et al , Zarrabeitia et al , Murphy et al and Ettinger et al . Subsequently, Stone et al 1998 found an inverse association between serum estradiol level and femoral bone loss among randomly chosen women (not using estrogen). They also found an inverse association between serum estradiol and bone loss at the calcaneus . Cummings et al 1995 found that higher estrone levels were associated with increased risk of incident vertebral fractures . The results of present study indicated that in postmenopausal women correlation of serum estradiol level with BMD was strongest at right femoral neck followed by lumbar spine and distal radius (r = 0.792, 0.670 and 0.594 respectively). With the increased longevity there is concomitant increase in the numbers of the elderly, particularly 12

Case Note

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

postmenopausal women, in developed as well as developing countries. There is a paucity of Indian study regarding serum estradiol level and bone mineral density in postmenopausal women.Due to a relative paucity of Indian studies in this field, and its high significance it is important that more studies to be done on this topic. Our study was therefore an attempt to bring to light the risk of osteopenia and osteoporosis in Indian postmenopausal women. This will help in counseling these subjects regarding the relevant lifestyle modifications and hormone replacement therapy. REFERENCES 1 Sacco SM, Ward WE — Revisiting estrogen: efficacy and safety for postmenopausal bone health. J Osteoporos 2010; 2010: 1-7 2 Simpson ER — Aromatization of androgens in women: current concepts and findings. FertilSteril 2002; 77: 6-10. 3 Nurhonni SA — Osteoporosis and Pencegahannya. Maj KedoktIndon 2000; 50: 565-8. 4 Ettinger B, Pressman A, Sklarin P, Bauer D, Cauley J, Cummings S — Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures. J Clin Endocrinol Metab 1998; 83: 2239-43. 5 Sowers MR, Jannausch M, Mc Connell D, Little R, Greendale GA, Filkelstein JS, et al — Hormone predictors of bone mineral density changes during the menopausal transition. J Clin Endocrinol Metab 2006; 91: 1261-7. 6 Tana L — Pencegahan osteoporosis. Media Litbang Kesehatan 2005; 15: 50-7. 7 Lindsay R, Cosman F: Osteoporosis In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson

JL, et al — Harrisons Principal of Internal Medicine. 17thed . United State of America 2008; 348: 2397-408. 8 Bagur A, Oliveri B, Mautalen C, Beotti M, Mastaglia S, Yankelevich D, et al— Low level of endogenous estradiol protects bone mineral density in young postmenopausal women. Climacteric 2004; 7: 181-8. 9 Rogers A, Saleh G, Hannon RA, Greenfield D, Eastell A — Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 4470-5. 10 Zarrabeitia MT, Hernandez JL, Valero C, Ziarrabeitia A, Amado JA, Macias JG, et al — Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density. Eur J Endocrinol 2007; 156: 117-22. 11 Stone K, Bauer DC, Black DM, Sklarin P, Ensrud KE, Cummings SR — Hormonal predictors of bone loss in elderly women: a prospective study. J Bone Miner Res 1998; 13: 1167-74. 12 Van Geel TACM, Geusens PP, Winkens B, Sels JPJE, Dinant GJ — Measures of bioavailable testosterone and estradiol and their relationships with muscle mass, muscle strength and bone mineral density in postmenopausal women: a cross-sectional study. Eur J Endocrinol 2009; 160: 681-7. 13 Murphy S, Khaw KT, Sneyd MJ and Compston JE — Endogenous sex hormones and bone mineral density among community-based postmenopausal women. Postgrad Med J 1992; 68: 908-13. 14 Mawi M — Serum estradiol levels and bone mineral density in postmenopausal women. Univ Med 2010; 29: 90-5. 15 Cummings SR, Nevitt MC, Browner WS — Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332: 767–77.

(Continued from page 24) 4 Shear CL, Burke GL, Freedman DS, Berenson GS — Value of childhood blood pressure measurements and family history in predicting future BP status: Results from 8 years of follow up in Bogalusa Heart Study. Pediatrics 1986; 77: 8629. 5 Update on the 1987 task force on high BP in children & adolescents — A working group report from the national high BP education program. Pediatrics 1996; 98: 649-58. 6 Fourth report on diagnosis, evaluation & treatment of high BP in children and adolescents. Pediatrics 2004; 114: 55575. 7 Stamler J — Blood pressure and high blood pressure: aspects of risk. Hypertension 1991; 18: 95-107. 8 Rames Lk, Clarke WR, Connor WE, Reiter MA, Lauer RM — Normal blood pressure and evaluation of sustained blood pressure elevation in childhood: the Muscatine study. Pediatrics 1978; 61: 245-1.

9 Fixler DE, Laird WP — Validity of mass blood pressure screening in children. Pediatrics 1983; 72: 459-61. 10 Sorof JM, Lai D, Turner J, poffenbarger T, Portman RJ — Overweight, ethinicity, and prevalence of hypertension in school aged children. Pediatrics 2004; 113: 475-82. 11 Gupta AK, Ahmed AJ — Normal blood pressure and the evaluation of sustained blood pressure elevation in childhood. Indian Pediatr 1990; 27: 33-42. 12 Verma M, Chhatwal J, George SM — Obesity and hypertension in children. Indian Pediatr 1994; 31: 1065-9. 13 Reddy KS — Cardiovascular diseases in the developing countries: dimensions, determinants, dynamics and directions for public health action. Public health Nutr 2002; 5: 143-69. 14 Gupta AK — Influence of family history of morbid cardiovascular events on blood pressure level to school children. Indian Pediatr 1991; 28: 131-9.

Tumoral mycetoma thigh without overlying sinuses — an unusual presentation S S Rathore , Mohan Lal , Anil Kumar 1

Usually Mycetoma presents as clinical triad of a subcutaneous mass, sinuses, and granular discharge, but in our case there was only cystic tumor. We present a case which was diagnosed preoperatively as tumour but intraoperative finding were suggestive of mycetoma & confirmed on biopsy. Extensive review of literature revealed only 2 cases of mycetoma presenting as cystic tumor without sinuses and granular discharge . 1,2

[J Indian Med Assoc 2016; 114: 29-30]

Key words : Cyst, Mycetoma, Tumoral, Eumycetoma, Actinomycetoma.

sinuses, and granular discharge, seen in patients from an endemic area, is diagnostic for mycetoma. The morphological characteristics and colour of the grains provides clues about the species of the agents . Many microorganisms are capable of causing mycetoma and several of these organisms seem to have their natural habitat in soil or plant materials including thorns. Madurella species are well known agents of black-grain mycetoma. Two species are recognized, M mycetomatis and M grisea . The most prevalent causative agent of eumycetoma is Madurella mycetomatis . Mycetoma initially presents as a slowly progressive and painless subcutaneous swelling, sometimes in combination with a history of preceding trauma . The subcutaneous swelling is usually firm and rounded but it can also be soft and lobular. It is rarely cystic , and is often movable. The subcutaneous nodule increases in size and secondary nodules might evolve as well . The nodules might suppurate and drain through multiple sinus tracts, and these sinuses can close transiently after discharge during the active phase of the disease. Fresh adjacent sinuses might open whereas some of the old ones might heal completely. The nodules are connected to each other through deep sterile abscesses, and to the skin surface . Most cases are usually seen in the feet (70%), followed by hands (12%), then legs and knee joints . In highly endemic areas, other parts of the body might become affected as well. Infection is more common in herdsmen, farmers, and other field laborers who are in frequent and direct contact with the field environment . Magnetic resonance imaging for instance has been shown to be informative in the detection and even identification of fungal grains and for the assessment of therapeutic success. Additionally, magnetic resonance imaging facilitates the detection of specific morphological features of the fungal grains (so-called dot-in circle signs) which are suggested to be highly specific for mycetoma lesions. Identification of etiological agent may require examination of grains, culture, biopsy, specific polymerase chain reaction . Proper management of mycetoma strongly depends on the identification of the causative organism. Actinomycetoma generally responds well to antibacterial treatment and, in a few cases, surgery is indicated. Eumycetoma should be treated with

45 year old man was admitted to our department with swelling over back of right thigh from last 4 years. From last 2 years patient feels on and off, non-radiating, dull aching pain in swelling. Examination — Patient’s vitals were within normal range. Swelling was 10cm x10cm in size, soft, cystic in consistency, mobile, non-pulsatile, without overlying sinuses, heavy to feel and visible veins. Swelling was not fixed to underlying structures. Peripheral pulses, sensation, movements of joints were normal. Patient have no history of similar swelling in past. No history of previous hospitalization. Investigations — Laboratory investigations including complete blood count, blood sugar, liver function tests were within normal range. CT SCAN of thigh shows well circumscribed complex fluid (20-22 HU) density non-enhancing cystic lesion in postero-medial right thigh in subcutaneous plane. It shows echogenic fluid with fluid debris level on USG screening & radiologist opinion was sebaceous cyst. Fine needle aspiration cytology show necrotic tissue. Our Preoperative suspicion was benign soft tissue cystic tumor e.g., mesenchymal tumor, sebaceous cyst. Management — Patient was prepared for excision of cystic tumor. On excision of swelling it showed black granules with yellowish fluid mixed debris. So it was suspected to be a mycetoma thigh and tissue was sent for histopathological examination. Patient was kept on tablet ketoconazole 400 mg oral daily for 9 months with regular monitoring of liver function. Patient is still on monthly follow up. Histopathology — Biopsy report was suggestive of Madurella mycetoma.

4,5

4-6

5,6

DISCUSSION

Mycetoma is a chronic granulomatous infection caused by true fungi (eumycetoma) or bacterial actinomycetes (actinomycetoma). The clinical triad of a subcutaneous mass,

Department of General Surgery, Dr S N Medical College, Jodhpur 342001 1 MS (General Surgery), Associate professor 2 MS (General Surgery), Senior Resident 3 MS (General Surgery), Assistant Professor 29

Case Note

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

adequate antifungal therapy and surgery . The most popular treatment regimes now a day for eumycetoma are Tablet ketoconazole 400–800 mg/day or Tablet itraconazole 400 mg/day orally for extended periods of time with a mean duration of 9-12 months. There are some sporadic case reports on the susceptibility of eumycetoma causative organisms to various antifungals including terbinafine, posaconazole, voriconazole, caspofungin and anidulafungin, but these need further clinical trials to establish their therapeutic potential, safety and efficacy for the treatment of eumycetoma . Mycetoma usually presents as clinical triad of subcutaneous mass, sinuses, granular discharge but our case presented unusually as a tumoral swelling at unusual site (thigh). Diagnosis was a more of intraoperative clinical surprise than a microbiological and histopathological surprise as preoperative clinical examination shows cystic tumor, fine needle aspiration cytology shows necrotic tissue, CT scan shows sebaceous cyst, but intraoperative finding of black granules made us suspect mycetoma and confirmed to be Madura mycetoma on microbiological and histopathological examination. 3

Acute intermittent porphyria : diagnostic and therapeutic challenges in India 1

Rupal V Dosi , Rushad D Patell , Gundurao alias Harsh M Joshi , Purav C Shah

Acute intermittent porphyria (AIP) is a rare metabolic disease involving a defect in heme biosynthesis resulting in accumulation and excessive secretion of porphyrins and its precursors. Acute attacks present with episodes of severe abdominal pain, nausea, confusion and severe life-threatening seizures. A high index of suspicion is required for the initial diagnosis of AIP. We present the case of a young male who presented with AIP succesfully treated with human hematin. [J Indian Med Assoc 2016; 114: 31-2] Fig 1 — CT SCAN showing cystic swelling

Key words : Acute Intermitent Porphyria, Human Hematin.

REFERENCES

1 Ly F, Develoux M, Deme A, Dangou JM, Kane A, Ndiaye B, Toure P — Tumoral mycetoma of the buttock. Ann Dermatol Venereol 2000; 127: 67-9. 2 AH Fahal, AM El Hassan, AO Abdelalla, HE Sheik — Cystic mycetoma: an unusual clinical presentation of Madurella mycetomatis infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 1998; 92: 66-7. 3 Abdalla OA Ahmed a, Willem van Leeuwen c, Ahmed Fahal b, Wendy van de Sande c, Henri Verbrugh c, Dr Alex van Belkum c — Mycetoma caused by Madurella mycetomatis: a neglected infectious burden. The Lancet Infectious Diseases 2004; 4: 566-74. 4 Boiron P, Locci R, Goodfellow M — Nocardia, nocardiosis and mycetoma. Med Mycol 1998; 36: 26-37. 5 McGinnis MR — Mycetoma. Dermatol Clin 1996; 14: 97104. 6 Fahal AH, Suliman SH — Clinical presentation of mycetoma. Sudan Med J 1994; 32: 46-66. 7 Ahmed Hassan Fahal — Management of mycetoma. Expert Review of Dermatology 2010; 5: 87-93.

Fig 2 — Intra operative finding showing cystic swelling with black granules

Know Your JIMA : www.ejima.in : jima1930@rediffmail.com : jimacir@gmail.com

For Marketing General

: :

jimamkt@gmail.com j_ima@vsnl.net

We request you to send Quality Articles addressed to : Hony. Editor, Journal of IMA (JIMA), 53, Sir Nilratan Sircar Sarani (Creek Row), Kolkata 700 014 Dr. Debasish Mukherjee Hony. Editor, JIMA

Table 1— Laboratory Investigations

CASE REPORT

If you want to send your queries and receive the response on any subject from JIMA, please use the E-mail facility. Website For Editorial For Circulation

systems including the abdomen and skin was not contributory. He was admitted in the intensive care unit, intubated and mechanical ventilation as well as other supportive mangement was begun. Hematological, biochemical investigations and a blood gas analysis were done (Table1). Urine was found to be pinkish and it further darkened on exposure to light (Fig 1), however no blood

cute intermittent porphyria (AIP) is a part of a group of disorders involved in defective heme biosynthesis resulting in accumulation and excessive secretion of porphyrins and its precursors. AIP is the second most common porphyria preceded only by porphyria cutanea tarda . Porphyrias present with acute episodes of severe abdominal pain, nausea, confusion and severe life-threatening seizures . A high index of suspicion is required for the initial diagnosis of AIP. We present the case of a young male who presented with AIP succesfully treated with human hematin.

Dr. Santanu Sen Hony. Secretary, JIMA Hony. Secretary, IMA Bengal

Test

A 18-year old male presented to us with complaints of generalized abdominal pain with fever, generalized tonic clonic convulsions and rapidly progressing bilateral symmetric weakness of all 4 limbs without ocular, bladder or bowel involvement over the past 4 months. A week before admission his relatives reported a gradual obtundation of sensorium and laboured respiration. The patient was hospitalized multiple times at various hospitals earlier for abdominal pain and fever and despite multiple evaluations including repeated endoscopies, an ultrasound and a CT scan of the abdomen no definite etiology of his abdominal pain had been identified. For his neurological complaints an extensive workup including a hematological profile, blood and CSF cultures and an MRI of the brain (that showed showed bilateral basal ganglia hyper intensity on T2 weighted images and FLAIR possibility of metabolic deposit/encephalopathy) had not pointed to a specific etiology. Moreover there was a positive family history of a similar condition in the sibling who passed away following a similar history without a definite diagnosis a year prior. On presentation, the patient was in respiratory distress. He was unconscious and did not respond to deep pain stimulation with reactive pupis. Glasgow Coma scale was 5/15. The patient had generalized hypotonia and areflexia. Examination of other

Hb (gm/dl) Total count (/cmm) Differential Count

Result

Normal Range

13.0 14.0-17.0 6800 4000-11000 74/22/4/0 P/ L/ E/B Platelet count 227000 150000-450000 ESR 12 Peripheral Smear Normocytic Normochromic RBCs, est normal Urea (mg/dl) 42 15-45 Creatinine (mg/dl) 0.9 0.8-1.3 Bilirubin (mg/dl)–Total 0.9 0-1 Direct 0.3 0-0.4 Indirect 0.6 0.2-0.8 SGPT (mcg/L) 104 <49 SGOT (mcg/L) 77 <49 Total protein (gm/dL) 7 6.5-8.5 Serum Albumin (gm/dL) 4.1 3.4-4.8 Sodium (mmol/L) 127 135-145 Potassium (mmol/L) 5 3.5-5.5 Random Blood Sugar (mg/dL) 123 Upto 140 Urine : Color Reddish brown Reaction Acidic Protein Absent Glucose Absent Pus cells Nil Red cells Nil Casts Nil Total porphyrins Positive Porphobilinogen Positive

Department of Medicine, Government Medical College & SSG Hospital, Vadodara 390001 1 MD (Gen Med), Additional Professor 2 MD (Gen Med), Senior Resident 3 MD (Gen Med), Assistant Professor 4 MBBS, Intern 31

Case Note

J INDIAN MED ASSOC, VOL 114, NO 10, OCTOBER 2016

or RBCs were detected. A qualitative screening test for porphobilinogen was strongly positive. This was confirmed by a 24 hour quantitiative test (28 mg/24 hour, normal <3.4 mg/24hour). Acute Poprhyria most likely Acute Intermittent Porphyria was diagnosed. Confirmation of the diagnosis requires enzymatic assay levels and genetic tests however, these are not available in India, and were thus not possible due to economic and logistic constraints. A nerve conduction study showed bilaterally symmetrical motor axonal neuropathy of all 4 limbs. The patient was treated with Heme Arginate (Normosang , Orphan Europe), 3 mg/kg/day for 4 days intravenously. After two weeks of intensive care , the patient was weaned off the ventilator and transferred to a general ward. GCS at the tme was 7/15, spontaneous eye opening was present however he was non responsive and immobile. A MRI brain at this juncture revealed focal symmetrical abnormal non enhancing signal abnormalities involving bilalteral capsuloganglionic, temporal and frontla lobe basal ganglia and thalami with leukomalacic cystic changes involving internal capsule exernal capsule and subcortical white matter on both sides (Fig 2). Over the course of the next two months he made an almost complete neurological recovery and at the time of writing this case report can ride a bicycle, write, perform personal hygiene and is infact preparing to return to school in the next academic year. TM

DISCUSSION

A majority of acute attacks of porphyria present with abdominal pain, dysautonomia and CNS symptoms. CNS manifestations include seizures, neuropathic pain, encephalopathy and global hyporeflexia . MRI changes usually 2

Fig 1: Pink urine darkened to deep red on exposure to light

Fig 2 : MRI reveals focal symmetrical abnormal non enhancing signal abnormalities involving bilalteral capsuloganglionic, temporal, frontal lobe, basal ganglia and thalami as well as internal capsule, exernal capsule and subcortical white matter on both sides.

include symmetric and reversible involvement of the cortical and subcortical areas of the occipital and parietal lobes. These changes are consistent with an evolving ischemic injury due to vasogenic edema and transient breakdown of blood brain barrier2,3. The urinary PBG test is the best initial test for the diagnosis of AIP and other porphyrias namely, hereditary corpoporphyria (HCP) and variegate porhyria (VP). Screening test is followed by a 24 hour urine sample is collected for quantitative measurement of amino levulinic acid (ALA), PBG and total porphyrins4. As the acute porphyrias are treated on similar lines, once there is definite laboratory documentation of a substantial increase in urinary or plasma PBG, treatment can be begun while further testing is in progress. The biochemical and genomic tests for definite diagnosis are not widely available. Although difficult to procure, Human hematin is the drug of choice in acute intermittent porphyria5. It reduces the overproduction of aminolevulinic acid which causes the symptoms of AIP, including encephalopathy and neuropathy. As only two companies in the world manufacture it, we had to make direct contact with the manufacturer in France. Besides raising the requisite sum (about two lakh rupees), special permission had to be sought from the Customs and the Central Drugs Standard Control Organization on an urgent basis to import it in. We managed to do this over the telephone with the cooperation of the concerned authorities over a few days and the patient received his first dose roughly a fortnight after admission. Hematin is known to reverse the neurological deficits in AIP. The neurological damage caused by accumulation of heme precursors is reversed by intravenous heme which does not cross blood-brain or bloodneuron barrier6. Early initiation of treatment can prevent long term neuropathy in AIP patients7. It is important to remember that, although a very difficult drug to obtain, heme produces excellent results in patients with AIP. Every patient with AIP should be given a trial of heme arginate before moving to alternate forms of therapy. The excellent recovery seen in our patient in a matter of months with complete reversal of encephalopathy and neuropathy further justifies the herculean efforts to overcome financial and bureacutic hurdles in obtaining and using this ‘wonder’ drug in AIP. REFERENCES 1 Puy H, Gouya L, Deybach JC — Porphyrias. Lancet 2010; 375: 924. 2 Pischik E, Kauppinem, R — Neurological manifestations of acute intermittent porphyria. Cell Mol Biol 2009; 55: 72-83. 3 C Gurses, A Durukan, S Sencer, S Akca, B Baykan, A Gokygit — A severe neurological sequela in acute intermittent porphyria: presentation of a case from encephalopathy to quadriparesis. Br J Radiol May 2008; 81: e135-e140. 4 Anderson KE, Bloomer JR, Bonkovsky HL — Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005; 142: 439. 5 Harper P, Wahlin S — Treatment options in acute p o rp h yri a , p o rp h yri a cu ta n e a ta rd a , a n d erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10: 444. 6 Watson CJ. Hematin and porphyria. N Eng J Med 1975; 293: 605-7. 7 Kuo H-C, Lee M-J, Chuang W-L, Huang C-C — acute intermittent porphyria with peripheral neuropathy: a follow-up study after hematin treatment. J Neurol Sci 2007; 260: 231-5.

Repeated pregnancy outcome in a case of takayasu arteritis 1

Subesha Basu Roy , Shilpa Basu Roy

Takayasu Arteritis (TA) is a chronic inflammatory progressive idiopathic disease that causes narrowing, occlusion and aneurysms of systemic and pulmonary arteries affecting mainly the aorta and its branches1,2. TA affects women of childbearing age. However, the optimal management for the disease in pregnancy has not yet been defined. The course seems to be neither affected nor worsened by pregnancy3,4. Here we describe a 38 years old post Caesarean section (CS) fifth gravida (G5 P1+3) who presented at 37 weeks& 5 days of gestation with activeTA disease. She had an emergency LUCS 1 year 4 Months ago, when at 34weeks a preterm baby was delivered &admitted in NCCU after birth. Our patient did not present with high blood pressure or features of aortitis. The course of her disease was unremarkable. [J Indian Med Assoc 2016; 114: 33 & 35]

Key words : Takayasu Arteritis, Pregnancy, Immuno suppressive therapy.

other routine blood investigation reports were within normal limits. She had a normal echocardiography report.

akayasu’s Arteritis (TA) is an inflammatory disease of the arter-ies that affects women of child bearing age . It is a rare chronic vasculitiswith unknownaetiologywhich was justly described in 1908 by the Japanese ophthalmologist Mikoto Takayasu. It has variable geographical distribution with the greatest prevalence in Asia, especially Japan. The women in their second and third decades of life are more commonly affected with an incidence of 80-90%thus, reflected in a synonym for TA as “young femalearthritis”. It is not uncommon to encounter the disease during pregnancy. Optimal management for pregnant patients with this disease has not yet been established due to the manifoldcardiovascular complications that can occur in the course of the disease. Management of pregnancies in TA patients is a challenge for the obstetrician, the rheumatologist and cardiologist. 2,5,6

Aortic & peripheral angiography (done 2 years ago) revealed a normal ascending and arch of aorta. The Innominate artery was grossly narrowed with normal bifurcation into right subclavian and carotid arteries. The lower half of descending thoracic aorta showed a reduction in luminal calibre with mild irregularity of wall. However, the upper part of abdominal aorta up to renal artery origin had a normal course, calibre and branching pattern. Severe narrowing was seen at the origins of the bilateral renal arteries. A 3-4cm segment of the abdominal aorta from the level of origin of the renal arteries showed near complete occlusion & only a thread like lumen was visualized. The part of the abdominal aorta distal to this narrowed segment showed normal course, calibre and bifurcation into bilateral common iliac arteries. The bilateral common, external and superficial arteries were grossly normal in course, calibre and branching pattern up to popliteal bifurcation. Ultrasonography (done around the same time) revealed a significantly smaller right kidney (measuring 9.5 x 4.5 cm) whereas the left kidney was of normal size. This may be attributed to renal artery stenosis. These findings were suggestive of Takayasu’s arteritis.

CASE REPORT

We describe a 38-year-oldpatient (G5P1+3) who presented at 37 weeks 5 days of pregnancy with H/O syncopal attack and intermitted claudication. Two years ago this patient was advised for a aorto-bi-iliac grafting by the Cardiothoracic & Vascular Surgery department of our Institute which she refused to undergo. On clinical examination all pulses were absent in the right upper limb. Pulses in all other limbs were normal. Cardiological examination was within normal limits.Bruits were audible over the right and left carotid and was louder on the right side. Blood pressure was 110/70 mm. of Hg measured on the left arm but unrecordable on the right arm. There was no history of fever. The neurological examination was normal. Laboratory values showedelevated C-reactive protein (10mg/dc) and total leukocyte count was 12,800/cu mm. All

Her latest aortic & peripheral angiographyshowed a long segment structureof abdominal aorta measuring 3.5cm. just below the origin of renal arteries. Pre-stenotic dilation (measuring 19mm in widest diameter) was noted. Multiple collaterals were noted in the region of narrowing connecting the pre-stenotic and post stenotic region of the aorta. There was narrowing in right renal artery near its aortic origin. All the branch arteries from the aortic bifurcation up to the arteria dorsalis pedis (in the bilateral lower limbs) revealed normal flow and was devoid of any significant stricture. Immunosuppressive therapy with high dose cortisone (methyl prednisolone 40 mg/day) was started. The ultrasound examination at 38 weeks gestation showed 2730 gm estimated weight of foetus

MBBS, MS, Assistant Professor, Department of Gynaecology & Obstetrics, IPGMER & SSKM Hospital, Kolkata 700020 2 MBBS, MS, MCh (CTVS), Medical Officer, Department of CTVS, IPGME&R & SSKM Hospital, Kolkata 700020 33

(Continued on page 35)

Case Note

TORSADE DE POINTES COMPLICATING CONGENITAL — MISHRA AND VIRADIYA

Torsade de pointes complicating congenital complete atrioventricular block in a pregnancy with pre-eclamptic toxaemia Ajay Mishra1, Kishor Viradiya1

A 30-year-old pregnant female presented for the first time with complete congenital atrioventricular block, pre-eclamptic toxaemia and disseminated intravascular coagulation. Torsade de pointes complicated the complete congenital atrioventricular block during the postpartum period. The electrocardiographic phenomenon of torsade de pointes was recorded. Prolonged QT interval with hypomagnesaemia was identified as the predisposing factor. Cardioversion and intravenous magnesium sulfate abolished the torsade phenomena. [J Indian Med Assoc 2016; 114: 34-5]

Key words : Torsade de pointes, congenital complete atrioventricular block, pregnancy, pre-eclamptic toxaemia.

ongenital complete heart block with prolonged QT interval is uncommon and has been reported mainly in paediatrics age group. Though there have been earlier reports of congenital complete heart block with pregnancy, to the best of our knowledge congenital complete heart block with prolonged QT interval complicated by pre-eclamptic toxaemia, disseminated intervescular coagulation and torsade de pointes in pregnancy has not been reported. Following, is a case report of congenital complete heart block and prolonged QT interval in pregnancy with preeclamptic toxaemia.

million/cmm, platelet count 5000/ml, prothrombin time (T) 21.2sec, (C) 16sec, INR 1.15, APTT more than 120 seconds, Ddimer 14.2mg (normal range- less than 0.5µg fibrinogen equivalent unit/ml), serum albumin 2.65mg/dl, total serum bilirubin of 1.65mg/dl with indirect bilirubin 1mg/dl, urine showed +3 proteinuria and arterial blood gase analysis was suggestive of respiratory alkalosis. Echocardiographic examination was normal. She had normal serum electrolytes, serum transaminases, renal and thyroid function. Her ANA profile and VDRL were negative.A diagnosis of congenital complete atrioventricular block with pre-eclamptic toxaemia and DIC due to abruptio placentae was made. Management — She received blood products and labour was induced. Temporary pacemaker was kept on standby. She was monitored during labour and successfully delivered a preterm live male baby. Retroplacental clot was detected on manual removal of placenta. No bleeding, syncopal or presyncopal symptoms or complex arrhythmia was noted during labour. During postpartum period she developed hypomagnesaemia (1.3mg/dl) (normal range-1.6-2.4mg/dl) and had an episode of polymorphic ventricular tachycardia (Fig 1) which reverted with cardioversion and intravenous magnesium sulfate. Thereafter, the postpartum period without prophylactic temporary pacing was uneventful and she was discharged.

CASE REPORT

A 30-year-old multigravida first presented at 32 weeks gestation with antepartum haemorrhage. She was found to be bradycardic. A resting electrocardiogram (ECG) showed complete atrioventricular block with a ventricular rate of 42/min, an atrial rate of 84/min, the QTc of 0.50second and QRS interval of 0.08 second. Intravenous atropine had no effect on the heart rate.A review of her past history suggested that she did not have recurrent sore throat, rheumatic fever, diphtheria or other illness which necessitated hospitalisation. No fainting attacks or undue fatigue complicated her activities during her previous pregnancies. No family history of sudden death or similar illness was noted among her other siblings and parents. Examination — Her blood pressure was 140/100 mmHg with pulse rate of 42/min at rest. There was severe pallor, mild icterus and pedal oedema. There was a soft systolic murmur to the left of the sternum heard best over the third intercostal space without thrill. Investigations — Her haemoglobin was 3.0 g/dl with total leucocyte count 1800cells/ml, red blood cell count 1.63

DISCUSSION

An increase in frequency of toxaemia has been suggested in patients with complete atrioventricular block . If activation time differences remain unchanged, the dispersion of repolarisation will be greater at slow than at fast heart rate. This increased dispersion might precipitate re-excitation or re-entry circuits of disorganised ventricular tachyarrthymias such as torsade and ventricular fibrillation . In the patient reported prolonged QT interval and hypomagnesaemia detected during the postpartum period increased her vulnerability to torsade de pointes ventricular arrhythymia. In 1

Department of Medicine, Pramukhswami Medical College, Karamsad 388325 1 MD, Assistant Professor 34

patients with increased ventricular repolarisation (long QT interval) a properly timed premature ventricular beat might induce ventricular arrhythmias . In the patient reported the possible mechanism of ventricular complex initiating the arrhythmia was probably hypomagnesaemia. Thus, congenital complete atrioventricular block is compatible with normal pregnancy. Congenital complete atrioventricular block is not so benign especially when associated with low ventricular or junctional rates with QT prolongation and electrolyte disturbance. Women with complete atrioventricular block without permanent pacing do not routinely require temporary pacing during labour, thereby avoiding the risks of such procedures . 3

REFERENCES

1 Mendelson CL — Disorders of the heart beat. In: Mendalson CL editor. Cardiac Disease in Pregnancy. Medical Care, Cardiovascular Surgery and Obstetrics Management as Related to Maternal and Fetal Welfare. 1st ed. Philadelphia: FA Davis Company, 1960: 302-25. 2 Han J, Malozzi AM, Chizzonitti B, Moe GK — Temporal dispersion of recovery of excitability in atrium and ventricle as a function of heart rate. Am Heart J 1966; 71: 481-7. 3 Schwartz PJ — Idiopathic long QT syndrome: progress and questions. Am Heart J 1985; 109: 399-411.

Fig 1 — Electrocardiogram Showing Torsade De Pointes Ventricular Arrhythymia Complicating Congenital Complete Atrioventricular Block 4 Hidaka N, Chiba Y, Kurita T, Satoh S, Nakano H — Is intrapartum temporary pacing required for women with complete atrioventricular block? An analysis of seven cases. BJOG 2006; 113: 605-7.

(Continued from page 33)

in utero with normal AFI and colour doppler study. She was posted for an elective caesarean section and delivered a healthy baby. The baby had an Apgar score of 8 and cried at birth. The peri-operative and post-operative period was uneventful. She was discharged from the hospital on the 7th post-operative day. Bilateral tuballigation was also done as patient had already completed her family and on medical grounds. DISCUSSION

TA is a rare chronic giant cell vasculitiswhich primary involves the aorta, its main branches and coronary and pulmonary arteries. The disease causes various clinical conditions such as arm claudication, decreased artery pulses, carotodynia, loss of vision, cerebrovascular accidents, aortic regurgitation, hypertension and congestive heart failure. Clinical presentation is extremely variable and may be insidious and its diagnosis is often delayed .The inflammatory reaction in TA responds to glucocorticoid which is the drug of first choice in pregnancy . If prednisone treatment fails, then azathioprine should be considered. Hypertension showed be treated very aggressively with alpha-methyl dopa, Calcium channel blockers or hydralazine . Pregnancy occurs more frequently in patients with TA than is patients with other forms of vasculitis. Our patient fulfilled all the criteria specified by the American College of Rheumatology (ACR) for the diagnosis of TA. She was under 40 years of age, complained of fatigue and muscle discomfort in the right arm and showed systolic blood pressure difference of more than 20mm of Hg since the right brachial artery pulse was not palpable. Carotid bruit was audible bilaterally but was louder on the right side.Although the Aortogram which was done 2 years ago showed vessel 7

8.9

abnormalities, there was evidence of presence of collaterals and normal blood flow to the arteries of the lower limbs in the latest aortic and peripheral angiogram. The course of her disease was stable and She was treated with high dose methyl prednisolone. The pregnancy was uneventful. REFERENCES

1 Bellin Y, Bernsteir H — successful epidermal anaesthesia for a patient with takayasu’s arteritis presenting for caesarean section. Can I anesth? 1993; 40: 64-6. 2 Ishikawa K, Matsumuva S — Occlusuic thromboaovtopally (Takayasu’s disease) and pregnancy. Clinical course and management of 33 pregnancies and deliveries. And J Cardiol 1982; 50: 1293-300. 3 Ioscovich A, Gislason R, Fadeev A — Periparhen anaesthetic management of patient with takayasu’s arteritis; case series and review. Int J Obstet Anesth 2008; 17: 35864. 4 Kathirvel S, Chavan S, Arya VK — Anaesthetic management of patients with takayssu’s arteritis: a case series and review. Anesth Analg 2001; 93: 60-5. 5 Matesumuva A, Moriwaki R, Numano F — Pregnancy in Takayasu artiritis from the view of internal medicine. Heart vessels Suppl 1992; 7: 20-4. 6 Seo P — Pregnancy and vasculitis. Rheumdischin North Am 2007; 33: 299-17. 7 Kerr G — Takayasu’s arteritis. Curr Opin Rheumatol 1994; 6: 32-8. 8 Ishikawa K — Natural history and classification of occlusive thromboaortopathy. Circulation 1978; 57: 27-35. 9 Noris M — Pathogeneses of Takayasu’s arteritis. J Naphvol 2001; 14: 506-13.

Branch Activities

Pictorial CME J INDIAN MED ASSOC

VOL 114, NO 10, OCTOBER, 2016

CAPUT MEDUSAE WITH CRUVEILHIER- BAUMGARTEN MURMUR : A SYNDROME OF CLINICAL SIGNIFICANCE A 21-years-old, unmarried young female was admitted to this hospital with history of progressively increasing abdominal distension and discomfort, generalised weakness, haematemesis and melaena since 2 months. There was no past history of jaundice. Clinically, she revealed pallor, massive splenomegaly with ascites and massively dilated, tortuous anterior abdominal veins radiating from umbilicus and lying mainly superior to it- caput medusae (Fig 1). There revealed Cruveilhier- Baumgarten murmur on auscultation and disappeared on epigastric pressure. Her investigations revealed Hb of 3.7 gm/dl, dimorphic anaemia with pancytopaenia, liver enzymes two-times elevated beyond the upper limit, endoscopic grade 3 oesophageal varices and no evidence of viral hepatitis or metabolic liver diseases. CT scan abdomen revealed shrunken liver, massive splenomegaly and ascites, dilated portal vein (18mm) and massively dilated porto-systemic collaterals including paraumbilical veins (Fig 2) suggestive of severe portal hypertension, consistent with findings of abdominal

ultrasonogram. She was diagnosed as a case of decompensated cirrhosis (cryptogenic), complicated portal hypertension, and dimorphic anaemia. She was treated with medical therapy with an advice for splenectomy and or shunt surgery. Cruveilhier- Baumgarten murmur, heard over umbilicus or xiphoid, significantly diminishes or disappears with epigastric pressure, is a venous hum, which originates from paraumbilical anastomotic veins and suggests massively dilated portosystemic collaterals of caput medusae in portal hypertension. Caput medusae with Cruveilhier- Baumgarten murmur is a syndrome of clinical significance as it goes a long way in the diagnosis of severe portal hypertension for initiation of early intensive management.

Department of Medicine, Dr Rajendra Prasad Government Medical College and Hospital, Kangra 176001 MD, Registrar MD, Professor and Head of the Department MS, Associate Professor of Surgery MD, Associate Professor and Head of the Department of Radiology

Laxmi Nand Dhiraj Kapur Atul Mahajan YP Sharma

Book Review "X-rays for Undergraduates" by Dr Mohd Adil Ali khan Siddiqui & Dr MA Mateen Siddiqui, 2nd Edition, Published by Paras Medical Publishers, 5-1-475, 1st floor, Putlibowli, Hyderabad 500095, India, 17.5 cm x 12 cm, pp 207. THE book contains a good no. of pictures of various pathologies that would certainly help the undergraduate students to get a good idea about the radiological features of the diseases. However, approach for reading a radiograph of different systems has been narrated a bit shorter, which may please be reviewed. Again short description about the newer imaging systems and the introduction chapter of basic Radiophysics may also be reviewed and edited in the next edition for attracting the interested and studious students.Finally it may be concluded that the book has been written in a acceptable easy language and so appears to be one of the good books presently in the Indian market for the undergraduate students.

Fig 2 â&#x20AC;&#x201D; CT Scan Abdomen Revealing Massively Dilated Anastomotic Paraumbilical Porto- Systemic Collaterals of Caput Medusae in Anterior Abdominal Wall (arrow) and Massive Splenomegaly

Sagore Dutta Hospital, Kolkata 36

Sankar Prasad Kabiraj 37

OCTOBER 2016

Vol. 114 No. 10

OCTOBER 2016

Vol. 114 No. 10

POST BOX NO. 11249

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION: IMA House, 53 Sir Nilratan Sarkar Sarani (Creek Row), Kolkata - 700 014 Phones: (033) 2236-0573, 2237-8092, Fax: (033) 2236-6437, E-mail : jima1930@rediffmail.com, Website: www.ejima.in ; www.ima-india.org, www.ima-india.org/ejima Head office: Indian Medical Association, IMA House, Indraprastha Marg, New Delhi - 110 002 Telephones: +91-11-2337 0009, 2337 8680, Fax: +91-11-2337 9470, 2337 0375, Telegram: INMEDICI, New Delhi - 110 002, Email: hsg@ima-india.org; Website: www.ima-india.org

OCTOBER 2016

Regd. No. WBENG/2557/57

Date of Publication : 30th Every Month

If not delivered please return to Journal of the IMA (JIMA) IMA House, 53 Sir Nilratan Sarkar Sarani (Creek Row), Kolkata - 700 014 (India)

Published and Printed by Dr Santanu Sen on behalf of Indian Medical Association and printed at Prabaha, 45A, Raja Rammohan Roy Sarani, Kolkata 700009, Editor: Dr Debasish Mukherjee, National President (IMA): Dr SS Agarwal, Honorary Secretary General (IMA): Padma Shri Dr KK Aggarwal. E-mail: hsg@ima-india.org; Website: www.ima-india.org