Ijcp January 2014

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ISSN 0971-0876

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Volume 24, Number 8

January 2014, Pages 701-800

Peer Reviewed Journal

yy American Family Physician yy Cardiology yy Drug yy ENT yy Neurology yy Obstetrics and Gynecology yy Ophthalmology

an i c i ys ians

yy Orthopedics

Phly Physic y l mi ami

yy Pediatrics yy Pharmacology yy

Fademy of F n ica Aca

Medifinance

er merican m A eA

yy Medilaw

ingurnal of th t a or d Jo

rp-reviewe o c In eer AP

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IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal Group Editor-in-Chief

Dr Veena Aggarwal MD, Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dr Chanchal Pal Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Orthopedics Dr J Maheshwari

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

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

Volume 24, Number 8, January 2014 from the desk of THE group editor-in-chief

705 Time to Start the New Year with a Difference

KK Aggarwal

Guest Editorial

706 Health Manpower Planning

Jayshreeben Mehta

709 Negligence in Medical Profession and Law

NV Ramana

American Family Physician

713 Hereditary Hemochromatosis

Brian K Crownover, Carlton J Covey

720 Practice Guidelines 723 Photo Quiz CARDIOLOGY

725 Comparative Evaluation of Angiotensin-Converting Enzyme Inhibitors for Their Beneficial Effects in Patients with Ischemic LV Systolic Dysfunction and Undergoing Coronary-Artery Bypass Surgery

PS Gandhi, RK Goyal, AR Jain, BS Mallya, MC Chag, VM Gupta, DS Shah, BR Trivedi, NA Shastri, CB Mehta, KA Jain, NS Bhavasar, UJ Shah

742 Acute Renal Failure and Silent Myocardial Infarction Following Multiple Honey Bee Stings

Kavina Marian Fernandes, Gadwalkar Srikant R, Shyamala G

746 Perioperative Myocardial Infarction

Sudivya Sharma, Prashast Jain

Drug

750 Spinosad: A Newer Anti-Lice Drug

AK Sharma, JK Kairi

ENT

753 Knowledge, Awareness, and Practices Among Patients with Thyroid Swelling Attending Cytology Clinic in a Medical College, Meerut

A Singh, B Sachan, NP Malik, VK Sharma, N Verma, CP Singh

756 Common Ear, Nose, and Throat Problems in Pediatric Age Group Presenting to the Emergency Clinic ‒ Prevalence and Management: A Hospital-Based Study

Kalpana Sharma, Dipen Bhattacharjya, Himajit Barman, Subodh Ch. Goswami

Neurology

761 Complex Regional Pain Syndrome Type 1 Treated with Vitamin C

SB Gondhali, SH Bhattad, G Nanoti, H Dua, B Asudani

Obstetrics and Gynecology Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

764 A Case Report on Female Pseudohermaphroditism: An Ambiguous Genitalia

K Tabassum, M Zulkifle, Yasmeen, M Nasar

ophthalmology

767 Management of a Complicated Case of Symblepharon with Amniotic Membrane Transplantation

Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com

P Jain, JP Chugh

Orthopedics

© Copyright 2014 IJCP Publications Ltd. All rights reserved.

770 Hansen’s Arthritis: An Overlooked Entity

The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Aashish Shejpal

PEDIATRICS

773 Asperger Syndrome in Adolescence: A Clinical Conundrum Complicated by DSM-5

Editorial Policies

DE Greydanus

Pharmacology

The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

778 A Comparative Analysis of Commercial Metformin Tablets

P Elango, Ramesh, S Shanmuganathan

AROUND THE GLOBE

784 News and Views

FORTHCOMING CONFERENCES

788 International Conferences eMEDINEWS INSPIRATION

789 A Story for Passover MEDIFINANCE

790 Medifinance MEDILAW

792 Medicolegal Queries

Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

eMEDI QUIZ

793 Quiz Time LIGHTER READING

796 Lighter Side of Medicine

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from the desk of THE group editor-in-chief Dr KK Aggarwal

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

Time to Start the New Year with a Difference

T

he Indian political system is going through a change and this change has started in Delhi. Most of us have always thought that this being the age of Kalyug, a change for betterment of the society was just not possible.

But this was our negative perception. When I hold motivational classes, I tell my audience to follow the routine as follows: ÂÂ Monday: Do not indulge in gossip, criticism, condemnation, and/or complaints. When you want to communicate,

do so in a nonviolent manner.

ÂÂ Tuesday: Talk to 25 people whom you have not spoken to for the last 3 months; make a list of your pending

work.

ÂÂ Wednesday: Distribute nonmaterialistic gifts to everyone you meet. Smile, appreciate, encourage, and say a

few kind words to others.

ÂÂ Thursday: Think out of the box and look for new and innovative options. Finally, ask yourself how to choose

the best option.

ÂÂ Friday: Follow nature and do not eat cereals. Be on a diet full of fruits and salads. ÂÂ Saturday: Ask yourself as to how you can help yourself, your family, your society, and your nation.

The above positive affirmations have changed me and my patients.

All of you who are reading this should try this and experience a change in yourself.

Wish you all a very Happy and Healthy New Year 2014.

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Guest Editorial

Health Manpower Planning (Message of Dr Jayshreeben Mehta, President MCI, at the 88th National IMA Conference and 74th Annual Meeting of the Central Council at Rajahmundry, Andhra Pradesh, December 27, 2013)

I

t gives me immense pleasure and satisfaction to be in the midst of this illustrious gathering that has assembled here. With all emphasis at my disposal, I would like to bring it to your kind notice that the development of health sciences is an important component of social and economic development. The basic fundamentals, equality, freedom, justice and dignity of individual, as envisaged in the Constitution are required to be kept in mind while planning the socioeconomic development of the country. India as a nation is committed to attainment for health for all by 2020 AD through the universal provision of comprehensive primary health care services.

In order to materialize this goal of rendering health services, health manpower turns out to be one of the most significant aspects for this attainment.

Health manpower has been defined as the “generation of people who are trained to promote health, to prevent and cure diseases, and to rehabilitate the sick.” The important dispensation required to be carried by the trained health manpower thus includes: promotive health, preventive health, curative health, and rehabilitative health.

Therefore, the primary aim of manpower planning is to make available the “right kind of personnel, in the right number, with appropriate skills, of the right place, at the right time, for doing the right job.” Manpower planning therefore is meant for training and deployment of the types and number of health personnel that is assessed on the basis of “need and affordability” as well. It is also imperative to ensure that such personnel is “socially responsible” and possesses an appropriate “technical, scientific, and managerial” competence. As such, health manpower planning therefore turns out to be an integral component of overall health planning and not an isolated entity.

India has more than 700,000 doctors of modern medicine, which is the second largest pool of medical doctors in the world. However, when compared with the population of more than 1,170 million, it is translated into a doctor population ratio of 60:100,000, which is below to that of the developed countries like USA, UK, and Australia. Even if the attributed doctors’ population ratio is taken at 100:100,000, there would be additional requirement of nearly 400,000 doctors.

The situation in availability of specialists manpower in India’s health sectors is even more alarming. Although the number of specialists in broad specialties of Internal Medicine, General Surgery, etc., being inadequate, is within manageable proportion, but the availability of specialists in emerging specialties like Psychiatry, Dermatology, Ophthalmology, Anesthesia, Radio-Diagnosis, Occupational Health and others, is much less.

Another dimension of the problem being faced by India is that of huge urban–rural divide. Although nearly 70% of the population lives in rural areas, only about 30% of the medical manpower is available in these areas.

It is in this context that the health manpower shortage needs to be evaluated. The planning commission has definitely thrown some light on the present manpower crunch plaguing the Indian health care industry, which will be further exaggerated for the high demand for Indian health care professionals around the world.

According to the report of the Planning Commission of India, India is short of 600,000 doctors, 1,000,000 nurses, and 200,000 dental surgeons; Indian doctors who have migrated to developed countries form nearly 5% of the total medical workforce. This shortage affects the efficiency of the doctors as they are overburdened.

As per the World Health Report 2006, India falls in the categories of countries with critical shortage of health service providers, which is often marked by inappropriate skill mixes and gaps in service coverage. Moreover, the health care manpower to population ratio in India is very low as compared to the global norms.

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Guest Editorial According to the report, doctor to patient ratio stands at 6 per 10,000 population in India that is much below than that of Australia being 249:1, in UK being 1665:5, and in US being 548:9. The shortage of medical practitioners is more acute in Indian states like Chhattisgarh and Jharkhand, with just two doctors for 100,000 people when with the global average is of 15 doctors per 10,000 populations. Similarly, the number of dental surgeons registered in India stands at just over 73,000 as against the requirement of 300,000. Currently, medical colleges in India churn out about 31,000 doctors apart from 20,000 dentists and 45,000 nurses. It is estimated that to meet the global average of 1.23 physicians and 2.56 nurses per thousand populations in the coming 15 years, India would require to open 600 new medical colleges (100 seats per college) and 1,500 nursing colleges as observed by Knowledge Commission in its report.

Against this backdrop, the brain drain of the qualified health manpower to other countries is yet another issue affecting the already grim health scenario. Almost 60,000 Indian physicians are estimated to be working in countries like US, UK, Canada, and Australia alone, a workforce equivalent to nearly 10% of the physicians registered with the Medical Council of India (MCI). There are high rates of “emigration” found among the nurses and paramedical staff also.

To cope up with these shortages, one of the strategies adopted by India was vertical and horizontal expansion of medical schools. At the time of independence in 1947, there were 23 medical colleges in India, which increased to 149 by the year 1993. In order to give fillip to the expansion of medical education without compromising the quality of medical education, the Indian Medical Council Act 1956 was amended in 1993 to regulate the medical education in the country by instituting a scheme prescribed under the Act through the MCI. In order to achieve the desired objectives of the amended Act, the Regulations pertaining to the Minimum Standard Requirements in a Medical College, Graduate and Postgraduate Medical Education, Teachers Eligibility, etc., were prescribed during 1997-1999. ln 1999 Regulations, in order to provide better health care facilities in the rural areas, the Council in its Establishment of Medical Colleges Regulations had prescribed certain conditions like the availability of unitary plot of land of 25 acres that would be easier to fulfil in rural areas wherein availability of open stretch of land is not a problem. This was done with a motive to ensure that the tertiary health care facilities which would have to develop in an apex hospital that is affiliated to a medical college would also be available in rural areas and also the graduates who have studied in rural surroundings would not find it a problem to settle in those areas once they graduate. Another vital change was reduction in the requirement of beds for a medical college of having annual intake capacity of 100 from 700 to 500. This was mainly done as it was observed that in the departments like Ophthalmology and ENT, the services were being provided mainly on day care basis. In the departments like Psychiatry and Skin & VD also, the focus was shifting from inpatient treatment to treatment on outdoor patient basis. All these measures resulted in the expansion of the medical colleges from 149 in 1993 to 381 at the end of 2013, thereby increasing the number of available undergraduate admissions to nearly 47,000 seats and approximately 30,000 graduates passing out of the medical colleges every year.

However, it is felt that even this increase is not sufficient to fulfil the increasing requirements of the health sector, mainly due to twin factors of providing better secondary and tertiary level services in a large hinterland that was not served with such secondary and tertiary level health care services as would have been desirable, and also to color 10 the rising expectations of ever-increasing population. Hence, in 2008, the Council has proposed several further amendments to the Minimum Standard Requirements Regulations that are briefly enumerated as follows: ÂÂ The 1997 Regulations had prescribed the requirement of land as a unitary piece of land of not less than 25 acres.

As such unitary plots of 25 acres were difficult to be acquired in urban areas having population of more than 2,500,000, hilly areas and tribal areas, this requirement was relaxed in urban areas having population of more than 2,500,000, hilly areas and tribal areas, wherein the medical college could be set up in two pieces of land. ÂÂ In order to achieve optimal utilization of the teaching faculty particularly in pre-clinical and para-clinical

departments, the faculty requirement was reduced by about 20% in these departments in such a manner that the quality of medical education would not be compromised.

ÂÂ The companies and corporates are also permitted to set up new medical colleges.

This will not only take care of the increasing requirement due to increasing population but will also ensure the availability of basic doctors for programs in rural areas like National Rural Health Mission, which are vital for the upliftment of health services in rural areas.

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Guest Editorial Simultaneously, in order to cater to fulfill the requirement of specialists, the MCI has also made available the total availability of nearly 12,000 seats in different postgraduate degree and diploma courses, including nearly 600 seats in different super specialty courses. Additionally approximately 5,000 openings are available under Diplomat programme in various subjects being offered by National Board of Examinations.

In order to make more specialists available, the teacher student ratio which was 1:1 is proposed to be relaxed to 1:2 in case of professor provided the institute would add 10 beds so that availability of postgraduate seats can be increased without sacrificing the quality of bed side teaching which is on utmost paramount factor in the postgraduate studies would not be compromised.

In order to ensure the availability of doctors in rural areas, the MCI has also proposed that at least 50% of the seats in postgraduate diploma courses should only be made available to those who have completed a specified minimum period of service in such areas for admission into postgraduate diploma courses. The Council has also suggested to the Government that such diploma holders should be given incentives so that they would revert back to their rural areas once they complete the diploma, thereby ensuring continuing availability of specialists in rural areas.

I would also like to mention here that the Indian Medical Association (IMA) is also keenly alive to these issues.

In order to make available expert medical manpower, the IMA has introduced “Aao Gaon Chale,” which means “Let us go to the Villages,” program wherein the doctors in their spare time and holidays visit to villages periodically, in order to provide the medical advice and treatment to the people who otherwise would never have on opportunity or access to the services in their surroundings. This program has met with huge success wherein so far it has been implemented successfully in 500 villages benefiting more than 100,000 people.

IMA has also actively taken up Government programs by way of public–private partnership initiative.

Such programs include tuberculosis control, family welfare, anemia detection and treatment, prevention of prenatal sex determination and sex selective abortion, and others. Services provided by private practitioners are complementary to Government efforts. These programs are implemented in more than 500 centers in five states.

IMA is also running AKN Sinha Institute of Medical Education and Research, Patna, India, that imparts postgraduate certificate courses in the form of distant learning programs on various subjects of common interest for family physician.

IMA College of General Practitioners looks after continuing medical education programs for family physicians so as to make better prepared for dealing with all sorts of medical emergencies in rural and backward areas. As such, it is necessary that the manpower plans are developed as a part of a more “bottom up” process with the requirements for manpower being considered alongside the requirements for other resources. It requires defining the health objectives, the services to be provided, and then identifying the resources including personnel requirements. lt is for these reasons I am of the considered opinion that an appropriate functional unison between MCI and the IMA is bound to pave good time for the genuine pursuit of quality-based medical education in the country resulting in effective generation of trained health manpower so as to deliver meaningful health care services to all the stakeholders to their satisfaction.

I thank the organizers for giving me this opportunity for putting across my candid views and I assure that MCI would always be open and available for a meaningful cooperation in the larger national and global interest with IMA at all times.

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Guest Editorial

Negligence in Medical Profession and Law (Message of NV Ramana, Chief Justice DHC, at the 88th National IMA Conference and 74th Annual Meeting of the Central Council at Rajahmundry, Andhra Pradesh, December 27, 2013)

“We have not lost faith, but we have transferred it from God to the medical profession.�

George Bernard Shaw So declared our ancient rishis! The doctor is verily the Lord Narayana Himself! When I see the galaxy of Doctors today, I am engulfed with an ecclesiastical feeling, because the Narayana Himself is present in his Virat Swaroopam.

No wonder, I deem it a singular honor to address you. I stand before you not with any authority to speak but with humility, bowing down to you in the most ancient order of the spiritual culture of India chanting Namo Narayana!

In fact, all religions hold the doctor in high esteem. Gautama Buddha said that a doctor is like a mother to each of his patients. As the mother with only child showers all her love and compassion on the child, the doctor should also do the same. Thus, an exceptionally venerable position is given to the doctor in all societies. But it is natural that greater the veneration given greater is the responsibility attached to live up to such privilege.

I feel privileged to be the guest today and to inaugurate the 88th National Conference of Indian Medical Association (IMA) and the 74th Annual Meeting of IMA Central Council, to be held today and tomorrow. I thank the organizing committee for inviting me and making me a part of this august gathering.

History of Rajahmundry Rajahmundry is a historic city situated on the bank of the river Godavari. Its rich heritage and history dates back to 191 AD. Distinctly located, Godavari Districts are known as the rice bowl of Andhra Pradesh. The first Telugu poet Adi Kavi Nannawa was born here, and he was the first who translated the epic Mahabharatha into Telugu.

Several freedom fighters belonging to this land sacrificed their lives and properties for our freedom struggle against the British rule. The great Kandukuri Veeresalingam was born here, who was an active social reformer and a huge supporter of widow remarriages in our history. He has encouraged education for women, has established a Telugu journal, and was also the first among the few writers to write prose for women. Godavari people are known for their hospitality.

Introduction The two important things we value are life and health. Doctors have the knowledge and skills that put them in a position to improve our health, treat our illness, and prolong or save our lives. The treatment of the patient and the medical information relating to his disease was once privy to the doctor and the medical profession; the advances in technology have made medical information available to any member of the public through the Internet.

The relation of the doctor and the patient was that of trust, but today high expectations of the patients and nonmeeting of such expectations by the doctors is straining their relationship.

We witnessed a pace of commercialization and globalization on all spheres of life and medical profession is no exception to this phenomenon. New advances in medicine and technology have improved health care for both patients and doctors.

Dr BM Hegde, a renowned cardiologist and former Vice Chancellor of Manipal University, in one of his articles sets out several ills of the present day medical system. One of the main complaints about the present medical system

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Guest Editorial is that it has become money oriented, with service to humanity taking the back seat. This is a serious complaint that we all have to think about. Another complaint is about excessive or unnecessary treatment and in certain cases even wrong treatment. Dr Hegde quotes Sir William Osler saying “one of the first duties of the physician is to educate the masses not to take drugs.” He further quotes Napoleon Bonaparte who said “Medicine is a collection of uncertain prescriptions the results of which, taken collectively, are more fatal than useful to mankind.”

Medical Profession and Law The doctor–patient relationship has undergone a sea change in the last two decades. The patient considered himself to be a consumer of the doctor for his professional service. The Consumer Protection Act, 1986, was enacted with the objective of safeguarding the interest of citizens who access health care. Section 2(1) (0) provides services means service of any description, the definition is not “exhaustive” but inclusive. However, it does not include rendering of any service free of charge or under a contract of personal service.

Section 2(1) (9) defines “deficiency” that includes all forms of professional negligence including medical negligence.

Negligence is the failure to exercise reasonable care. Professionals like doctors are expected to exhibit wisdom as well as technical ability and reasonable care to patients.

Medical Negligence “Medical negligence” is the breach of reasonable care toward patients. Basically, three pertinent issues evolve in cases of medical negligence; they are: ÂÂ Whether the doctor, who was dealing with the patient at that particular point of time, was having proper

medical skills?

ÂÂ Whether the doctor used medical skills and practices as responsible practitioner in the field? ÂÂ Whether the standard of skill or knowledge and duty expected from the doctor was followed when the

allegation of negligence occurred?

The Hon’ble Apex Court responding to the need of the hour developed and elaborated the jurisprudence of medical negligence. In Samir Kohli’s case, it was held that when the patient is adult and capable of giving consent, the doctor should obtain consent from him when there is no emergency.

In Jacob Mathews case, Supreme Court has laid down the principles on “Medical negligence” and held that it is not possible for every professional to have the highest level of experience or skill, but it is sufficient if he exercises the ordinary skill of an ordinary competent man exercising that particular act, and further the concept of negligence between civil law and criminal law was also discussed. The Apex Court in Martin F D’Souza’s case held that whenever a complaint for medical negligence is filed, the matter should be referred to a competent doctor or committee of doctors specialized in the relevant field; when such experts feel that there is prima facie case, then only the notice should be issued to the doctor to avoid harassment caused to the doctor.

As you all are aware, recently on October 24, 2013, in Balaram Prasad’s case, the Apex Court, while rejecting the plea of IMA that medical practitioners cannot be treated as service providers in term of Section 2(1)(0) of the Consumer Protection Act, held that hospitals and doctors are liable for negligence and enhanced the compensation from Rs. 1.73 crores to Rs. 5.96 crores.

In cases of medical negligence, the Courts in India are following two principles, one is limited liability and the second is based on the highest degree of care toward the patient and his relatives, as the professionals are responsible and accountable. In limited liability: (1) mere deviation from normal professional practice is not negligence, (2) an error in judgment on the part of professional is not negligence per se, and (3) when patient does not respond favorably to a treatment given by a doctor, he cannot be held liable.

Although the field of medical negligence is a new emerging area of law in the context of corporatization of health care, yet what constitutes “medical negligence” has now been well settled in view of a number of judgments of the Apex Court. I feel doctors practicing ethically and honestly should not have any reason to fear. Doctors claiming to adhere to ethics have always lamented that colleagues stooping to unethical practices have an unfair advantage because there is no control over those practices. The Consumer Protection Act will help in curbing these unfair

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Guest Editorial advantages and the Act is definitely good for medical practitioners, who believe in principles and ethics. Therefore, the medical professionals need to update their understanding on Consumer Protection Act and its amendments that are on a legally safer side: if doctors would like fewer legal restrictions on themselves, they must regulate through adherence to the principles of medical ethics.

Social Responsibility and the Constitution Success in one’s career is certainly a goal to be pursued. We should, however, not lose sight of the fact that a large number of our less favorable brothers and sisters are in urgent need of help. Ideally, all of us should devote a portion of our life to community service. The silent suffering of millions of people in our country cannot be ignored. India is one of the poorest countries in the world. Poverty in India involves poverty in every aspect of life.

Inequality continues to destroy India like any other developing countries. The rich become richer while the poor becomes poorer. Without health, no progress is possible. Therefore, a duty is cast upon the State to provide to its citizens a good and healthy life. Article 21 of the Constitution provides for protection of life and personal liberty, which includes in its ambit, right to health and medical care to all its citizens. Article 47 of the directive principles of state policy ordains a duty on the State to raise the level of nutrition and the standard of living and to improve public health. Despite constitutional provisions, providing better health care to citizens was never a top priority in India. To meet the medical needs of millions, we must evolve an integrated system of medicine, which will best suit our country having regard to its geographical conditions and socioeconomic needs and keeping in view its available limited resources.

In our country, we have the best physicians and surgeons. But we lack in terms of qualified medical technicians and supporting staff. Although India remained a major supplier of doctors and nurses to the developed countries over the years, domestic scenario looked bleak with the country ranking 67th among the developing nations in the case of doctor–population ratio. A fees levying private health care sector comprises of 82% of overall health expenditure.

While less than 1% of population is covered by health insurances, the challenges are enormous.

According to the report by the United Nations, 75% of the health infrastructure in India, including doctors, specialists, and other health resources, are concentrated in urban area, where only 27% of Indian population lives.

The rural population of India is around 716 million people, that is, 72%, yet there are no proper medical facilities for them. Today, rural India faces a shortage of more than 12,300 specialized doctors. There are vacancies for 3,880 doctors in the rural health care systems and a need for 9,814 health care centers; 66% of rural population of India lacks access to preventive medicine and 31% of the rural population in India has to travel 30 km to get needed medical treatment.

Responsibility of the Government The government on its part needs to take certain policy decisions by allocating sufficient budget for health care.

It needs to strengthen public health care system. The US, Australia, and UK has strong provision for health care.

Unfortunately, India being poor, its citizens are paying the price. Government should provide enabling environment and achieve universal health care. The country graduates 27,000 doctors each year, but all of them want to work in major cities or pursue higher studies abroad. I personally feel that there is nothing wrong. If a doctor chooses to work in a remote village with a service motto, he is handicapped because there is no infrastructure; there are no qualified medical technicians and supporting staff. Although the doctor has enough knowledge and skill, practically he is not able to serve the people to the best of his ability and ultimately he is left with dissatisfaction, whereas his colleagues, who are working in the cities and abroad, are able to do a better job than him and are able to prove themselves. Strengthening the public health care system is the need of the hour. Government should implement a uniform health care policy, wherein we should see a day when all the citizens of India, irrespective of their social status, receive equal medical facilities and no one is deprived of his fundamental rights guaranteed under the Constitution. I would like to appeal to the members that each and every one should make it a point to spend a day in a month in the service of underprivileged people of the society.

Duties of MCI The MCI and IMA should make joint effort and should improve quality of medical education and effectively enforce medical ethics. The Institutions have failed miserably in curbing rampant quackery. The professional bodies

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Guest Editorial like MCI and IMA need to work efficiently in coordination with each other toward restoration of public faith in the system. Another solution is to educate and empower patients as equal partners, important stakeholder toward delivery of patient centric care. The common man needs to be educated and enlightened on the basic health issues, hygiene, because it is said that “prevention is better than cure.” An enormous responsibility is cast upon the doctors in educating the patients and making them understand about the basic precautions to be taken, hygiene and other issues, which will minimize the health-related problems.

Expectations The modern medicine should aim at a holistic approach following the advice of Hippocrates that says “Cure rarely, comfort mostly but console always,” with the advent of the corporate culture. In the medical world, the personal relation between doctor and patient is totally missing, which is a vital component in the health care. Hardly anyone talks with the patients these days. Most of the big bosses make what they call the “chart rounds” in the ward side rooms where all the details of the patients including the scans and X-rays are kept. Little time is spent on the bedside.

It must be remembered that as professionals, you have the higher ideals and standards to uphold. The medical profession needs input from a belief in humanity and the ethics more than professionalism. There is no definition for a perfect doctor. A good doctor is one who is truly mindful of his/her personal and professional limitations and treats the patient with utmost compassion and sheer humanity, regardless of who they are. Above all, a doctor should have a human touch, where they can perceive and understand the tone of human relations and their sufferings.

In spite of several issues, still people have lot of faith in doctors and they believe only doctor after God. I hope and trust that the Indian Medical Community, through this Conference, will take fruitful and deliberated discussions in tune with the mottoes of the IMA, which are promotion and advancement of medical and allied sciences in all their different branches, improvement of public health and medical education in India, and maintenance of honor and dignity of the medical profession, for which it was established.

The medical education has to be streamlined, teaching methodology and examination patterns need reforms. The archive methods of testing the talent of medical students have to be changed. As a Judge, I am coming across a vast number of cases from the student community about the harassment made in the hands of professors during awarding marks. Therefore, I request the IMA to sensitize the problems of medical students to the teaching community.

As Gurudev Rabindranath Tagore said “let life be beautiful like summer flowers and death like autumn leaves.”

The medical world should precisely aim at that instead of prolonging a person’s life on a ventilator in a vegetative state.

I thank you one and all for your patient hearing. I wish you all the best and, in advance, a Happy New Year 2014.

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American Family Physician

Hereditary Hemochromatosis BRIAN K. CROWNOVER, CARLTON J. COVEY

Abstract Hereditary hemochromatosis is an autosomal recessive disorder that disrupts the body’s regulation of iron. It is the most common genetic disease in whites. Men have a 24-fold increased rate of iron-overload disease compared with women. Persons who are homozygous for the HFE gene mutation C282Y comprise 85 to 90 percent of phenotypically affected persons. End-organ damage or clinical manifestations of hereditary hemochromatosis occur in approximately 10 percent of persons homozygous for C282Y. Symptoms of hereditary hemochromatosis are nonspecific and typically absent in the early stages. If present, symptoms may include weakness, lethargy, arthralgias, and impotence. Later manifestations include arthralgias, osteoporosis, cirrhosis, hepatocellular cancer, cardiomyopathy, dysrhythmia, dia­betes mellitus, and hypogonadism. Diagnosis requires confirmation of increased serum ferritin levels and transferrin saturation, with or without symptoms. Subtyping is based on genotypic expression. Serum ferritin measurement is the most useful prognostic indicator of disease severity. Liver biopsy is performed to stage the degree of fibrosis with severe ferritin elevation or transaminitis, or to diagnose nonclassical hereditary hemochromatosis in patients with other genetic defects. Treatment of hereditary hemochromatosis requires phlebotomy, and the frequency is guided by serial measurements of serum ferritin levels and transferrin saturation. Iron avidity can result from overtreatment. If iron avidity is not suspected, it may mimic undertreatment with persistently elevated transferrin saturation.

Dietary modification is generally unnecessary. Universal screening for hereditary hemochromatosis is not recommended, but testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results. Screening for hepatocellular car­cinoma is reserved for those with hereditary hemochromatosis and cirrhosis.

Keywords: Hereditary hemochromatosis, autosomal recessive disorder, serum ferritin measurement, liver biopsy, hepatocellular car­cinoma

I

ron is essential for cell metabolism and is a constituent of hemoproteins, such as hemoglobin, myoglobin, and cyto­ chrome P450.1,2 Consequently, total body iron levels are precisely regulated under normal physiologic conditions. Hereditary hemochromatosis is an autosomal recessive disorder in which iron regulation is dis­rupted, resulting in the toxic accumulation of iron in vital organs and the development of cirrhosis, bone and joint disease, diabetes mellitus, and heart disease.

Hereditary hemochromatosis is associated with malignancies, particularly hepatocel­ lular carcinoma.

Approximately 6 percent of patients with hereditary hemochromatosis and cirrhosis develop hepatocellular carci­noma; this represents a 20-fold increased lifetime

BRIAN K. CROWNOVER, MD, FAAFP, is program director of the Nellis Fam­ily Medicine Residency, 99th Medical Group, Nellis Air Force Base, Nev., and an assistant clinical professor at the Uniformed Services University of the Health Sciences in Bethesda, Md. CARLTON J. COVEY, MD, is a faculty member at the Nellis Family Medicine Residency and an assistant clinical professor at the Uniformed Services University of the Health Sciences.

Source: Adapted from Am Fam Physician. 2013;87(3):183-190.

risk over the general population and a 4 per­cent annual incidence rate.3 The mechanism for increased risk is the effect of excess iron in pro­moting oxidative DNA dam­ age and free radical activity. Increased iron stores also may increase the risk of breast cancer,4,5 although the lit­erature is limited and conflicting. A 2007 prospective cohort study showed no associa­tion between female breast cancer and total body iron stores.6 In contrast, a 2011 cohort study showed a statistically significant cor­relation between breast cancer and elevated levels of iron-bound ferritin in the breast microenvironment.7 Iron overload causes restrictive cardio­ myopathy, diastolic dysfunction, heart fail­ure, dysrhythmias, and conduction defects, which may lead to atrioventricular block, bradyarrhythmias, tachyarrhythmias, and sudden cardiac death. Iron-overload car­diomyopathy is reversible if therapy begins before the onset of overt heart failure.8-11 Excess iron deposited in hepatocytes results in toxicity that can lead to cirrhosis, which may be the most important prognos­tic factor in patients with hereditary hemo­chromatosis. Survival may be shortened in those with cirrhosis or diabetes; early diag­nosis and treatment may prevent morbidity and mortality.12 The five-year survival rate in patients who have

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American Family Physician untreated hereditary hemochromatosis and cirrhosis is reduced by 50 percent compared with those who do not have cirrhosis.12 Furthermore, patients with hereditary hemochromatosis who consume more than 60 g of alcohol per day (about four servings) have a nine­fold increase in the incidence of cirrhosis.13 Genetics In patients with hereditary hemochromatosis, the prin­ cipal gene defect alters the expression of the HFE protein responsible for regulating hepcidin, the primary iron regulatory hormone.14 In response to excess iron, hepa­ tocytes secrete hepcidin, which decreases intestinal iron absorption by enterocytes and decreases iron release by macrophages. This maintains iron levels in a physiologic range. When the HFE gene exhibits a missense mutation at amino acid position 282, the protein product (C282Y) causes decreased hepcidin expression in response to ele­vated iron levels and subsequent unregulated control of iron levels.15,16 Approximately 85 to 90 percent of affected patients are homozygous for the C282Y mutation.17 Hereditary hemochromatosis is more common in white populations of northern European origin and is highest in Ireland17; the prevalence ranges from one in 150 to 250 persons18,19 (Table 1).19 However, because only 10 percent (one in 2,500) of those with C282Y homozygosity pres­ ent with end-organ damage or clinical manifestations of hereditary hemochromatosis, most persons who are posi­tive for hereditary hemochromatosis are asymptomatic.14,20 Although other minor HFE gene mutations exist, they rarely are associated with iron-related organ damage.

For this reason, this article focuses on hereditary hemochro­ matosis related to C282Y homozygosity Table 2.21

or prolonged use of continuous oral contraceptives.

With the advent of genetic testing, the average age at diagno­ sis is similar for men and women. However, women have less severe disease manifestations. One large cohort fol­lowed persons homozygous for C282Y for 12 years and showed iron-overload disease in 28.4 percent of men but only 1.2 percent of women, a 24-fold increase.22 The most common presenting symptoms are weakness, lethargy, impotence, and arthralgias23 (Table 314,17,20,24,25). Physical findings may involve multiple organ systems. Many features are suggestive of disease processes other than hereditary hemochromatosis. Given these poten­tially protean presentations, an iron panel can promptly rule out iron-mediated organ dysfunction.

All patients with abnormal liver function test results or other indi­ces of liver disease should be evaluated for hereditary hemochromatosis.14 Diagnosis The diagnosis of hereditary hemochromatosis requires increased iron stores, with or without symptoms. Subtyp­ ing is based on genotypic expression. C282Y homozygos­ ity in the absence of elevated iron stores is not diagnostic for hereditary hemochromatosis, although such persons would have genetic susceptibility of developing it in the future. Initial laboratory studies include serum ferritin levels and transferrin saturation, which is calculated by dividing the serum iron concentration by the total ironbinding capacity (both measured in mcg per dL), and then multiplying by 100 percent (normal range is 16 to 45 percent). Because serum iron may be affected by food or drink, fasting traditionally has been recommended when drawing iron studies. However, newer data cast doubt on this.20,26,27 It is no longer a requirement for patients to be fasting when laboratory studies are drawn.

Persons with hereditary hemochromatosis usually are asymptomatic, especially in the early stages. When pres­ ent, symptoms are vague and nonspecific. Additionally, patients rarely present with the classic “bronze diabetes” clinical triad of cirrhosis, diabetes, and bronze skin pig­ mentation. Hereditary hemochromatosis is exceedingly rare in some races, such as Asians, Hispanics, blacks, and Pacific Islanders.

Figures 114,28 and 228 present algorithms for the diag­ nosis and management of hereditary hemochroma­ tosis. All persons with suggestive symptoms, physical findings, or a family history of hereditary hemochro­ matosis should have transferrin saturation and serum ferritin levels tested. If transferrin saturation or serum ferritin levels are elevated, then HFE mutation analysis should be performed. In children who have one parent with hereditary hemochromatosis, negative iron studies rule out hereditary hemochromatosis if the other parent does not have it.

Symptomatic hereditary hemochromatosis rarely presents in persons younger than 40 years. In women, menstruation delays iron accumulation; therefore, symptoms usually begin after menopause, hysterectomy,

Serum ferritin concentration correlates with total body iron stores. A normal serum ferritin level with transferrin saturation less than 45 percent has a negative predictive value of 97 percent for excluding iron over­

When to Suspect

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American Family Physician Table 2. Hereditary Hemochromatosis Subtype Classification System Type 1—classical HFE gene mutations resulting in a cysteineto-tyrosine substitution at amino acid 282 (C282Y) or an aspartate-to-histidine substitution at amino acid 63 (H63D)

Diagnosis of Hereditary Hemochromatosis in Adults Patient is symptomatic

Patient is asymptomatic with abnormal iron study results or evidence of liver disease

Type 2—nonclassical (also known as juvenile hemochromatosis) resulting from mutations in iron regulatory protein, hemojuvelin (HJV gene) Type 3—nonclassical resulting from mutations in the transferrin receptor protein 2 (TFR2 gene) Type 4—nonclassical resulting from mutations in the iron exporter, ferroportin (SLC40A1 gene) Note: Type 4 is the only type that is inherited as an autosomal dominant condition; types 1 through 3 are inherited as autosomal recessive conditions.

Information from reference 21.

Table 3. Clinical Symptoms and Physical Manifestations in Patients with Hereditary Hemochromatosis Abdominal pain

Hepatomegaly

Amenorrhea

Hypogonadism

Apathy

Hypothyroidism

Arthralgias

Impotence

Ascites

Increased pigmentation (bronze diabetes), rare late finding

Cardiomyopathy Cirrhosis Congestive heart failure Cutaneous manifestations of chronic liver disease (e.g., spider nevi, palmar erythema)

Measure random serum ferritin level and transferrin saturation

Transferrin saturation < 45 percent and normal serum ferritin level No further testing needed

Transferrin saturation ≥ 45 percent and/or elevated serum ferritin level (> 300 ng per mL [674.10 pmol per L] in men or > 200 ng per mL [449.40 pmol per L] in women) Proceed to HFE gene testing

Joint swelling, especially second and third metacarpophalangeal joints Lethargy Loss of libido

Patient has a firstdegree relative with hereditary hemochromatosis

Heterozygous for C282Y

Homozygous for C282Y

Refer to gastroenterologist and/or hematologist for further workup and possible liver biopsy

See Figure 2

Osteoporosis

Figure 1. Algorithm for the diagnosis of hereditary hemo­ chromatosis in adults 18 years and older.

Diabetes mellitus

Splenomegaly

Information from references 14 and 28.

Dysrhythmias

Testicular atrophy

Esophageal varices

Weakness

Hepatocellular carcinoma

Weight loss

Information from references 14, 17, 20, 24, and 25.

load.29 Additionally, serum ferritin measurement is the most important prognostic test in persons with heredi­ tary hemochromatosis: a level less than 1,000 ng per mL (2,247 pmol per L) predicts the absence of cirrhosis (Table 530-33). However, an elevated serum ferritin level is not diagnostic for hereditary hemochromatosis; the positive predictive value for detection of C282Y homozy­ gotes ranges from 1.6 to 17.6 percent.17 HFE mutation analysis has decreased the use of liver biopsy, which is typically reserved to determine the

degree of fibrosis or cirrhosis in persons homozygous for C282Y who have a serum ferritin level of at least 1,000 ng per mL. Persons with cirrhosis are possible candidates for liver transplantation after evaluation by a gastroenterologist or hematologist. In patients with C282Y heterozygosity and severely elevated ferritin levels, liver biopsy or noninva­sive specialized magnetic resonance imaging techniques may be used to determine the degree of hepatic iron con­ tent or to diagnose 14 nonclassical hemochromatosis.

Treatment All patients with homozygous hereditary hemochro­ matosis and evidence of iron overload (i.e., transferrin saturation greater than 45 percent and serum ferritin

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American Family Physician Management of Homozygous Hereditary Hemochromatosis Measure serum ferritin and liver transaminase levels Counsel on decreasing or eliminating alcohol intake

Serum ferritin level < 1,000 ng per mL (2,247 pmol per L) and normal liver transaminase levels

Serum ferritin level ≥ 1,000 ng per mL or elevated liver transaminase levels Refer to gastroenterologist for liver biopsy to determine hepatic iron content and histopathology

Begin iron reduction therapy: Weekly phlebotomy with a goal serum ferritin level of 50 to 150 ng per mL (112.35 to 337.05 pmol per L) Maintain hemoglobin level > 12.5 g per dL (125 g per L) Evaluate liver, heart, and endocrine function; perform screening hepatic ultrasonography If evidence of cirrhosis, characterize any hepatic ultrasonography findings

No liver lesion; Lesion < 1 cm; screen every six to screen every three 12 months to six months and consult a gastroenterologist

Lesion ≥ 1 cm; refer to gastroenterologist to evaluate for hepatocellular carcinoma

Figure 2. Algorithm for the management of patients with homozygous hereditary hemochromatosis.

Information from reference 28.

level greater than 300 ng per mL [674.10 pmol per L] in men and greater than 200 ng per mL [449.40 pmol per L] in women) should be treated, regardless of symp­ toms. Although randomized controlled trials have not been performed, the standard of care is phlebotomy to reduce total body iron levels and achieve normal ferritin levels. According to expert opinion, goals for serum ferritin levels vary between 50 and 150 ng per mL (112.35 and 337.05 pmol per L).14,20 Each 500-mL unit of whole blood (200 to 250 mL of packed red blood cells) removes 200 to 250 mg of iron and reduces serum fer­ritin levels by approximately 30 ng per mL (67.41 pmol per L).34 Hemoglobin levels should be checked before each phlebotomy, and therapy typically is withheld when the hemoglobin level is less than 12.5 g per dL (125 g per L). Patients should adhere to general

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population colon cancer screening guide­ lines during treatment, especially if iron deficiency ensues.

Published guidelines are available to guide phlebotomy frequency.35 Expected benefits of therapeutic phlebotomy include the following: a reduction of tissue iron stores to normal levels; resolution of fatigue and lethargy; marked reduction in skin bronzing/pigmentation; marked improve­ment in hepatic enzyme abnormalities, right upper quadrant pain, and hepatomegaly, if initially present; hepatic fibrosis reversal in 30 percent of cases; improved cardiac function; and occasional improvement in diabetes control.14,36 However, phlebotomy treatment will not reverse established cirrhosis or sig­nificantly improve arthropathy, testicular atrophy, or thyroid dysfunction.14 If patients are intolerant of phle­botomy, iron chelation therapy is a second-line option.

Iron avidity is a complication of phlebotomy. Defined as an ardent desire or craving for iron, this condition repre­ sents overcorrection of iron overload. Clinically, patients will have low or normal levels of serum ferritin (the stor­ age form of iron), yet have elevated transferrin saturation (the mobilized form of iron). Because elevated transfer­ rin saturation is an initial indicator of hereditary hemo­ chromatosis, these laboratory findings may be difficult to reconcile, leading to an underappreciation of iron avidity. If iron avidity occurs, it may have an associated anemia requiring evaluation for a gastrointestinal source of bleed­ing. Paradoxically, the treatment of iron avidity in patients with hereditary hemochromatosis may include iron supplementation until transferrin saturation and serum ferritin levels return to normal; alternatively, patients can be observed for spontaneous correction.37 Waivers for blood centers may be granted to allow hereditary hemochromatosis blood to be used for trans­ fusions; therapeutic phlebotomy may be performed free of charge with a physician’s order.38 Currently, the American Red Cross has a variance (waiver) from the U.S. Food and Drug Administration, but accepts blood donations from persons with hereditary hemochroma­ tosis only at certain locations.39 The Iron Disorders Insti­ tute Web site provides a list of treatment centers (http:// www.irondisorders.org).20 Dietary modification is generally unnecessary. Iron balance normally is maintained tightly; the daily dietary amount absorbed matches the amount lost each day within sloughed cells, or approximately 1 mg.40 Given that patients with hereditary hemochromatosis can absorb up to 4 mg of iron daily, iron supplements should be avoided, as well as vitamin C supplementation.

The American Association for the Study of Liver Diseases (AASLD) rec­ommends no meal selection

American Family Physician Table 5. Cirrhosis Rates in Patients with Hereditary Hemochromatosis Elevated serum ferritin level*

Elevated ALT or AST level

Platelet count†

Excessive alcohol use

Cirrhosis rate (%)

No

No

No

No

0

Yes

No

No

No

20 to 45

Yes

Yes

Yes

No

80

Yes

Yes

Yes

Yes

> 80

ALT = alanine transaminase; AST = aspartate transaminase. *Greater than 1,000 ng per mL (2,247 pmol per L). †Less than 200 × 103 per μL (200 × 109 per L).

Information from references 30 through 33.

adjustments, because 4 mg per day of dietary iron intake is small compared with the amount of iron that is removed with phlebotomy (250 mg per week).14 Although other groups recommend specific dietary changes to reduce serum iron levels, no data have shown that dietary manipulation improves patient out­comes.20 Of note, raw shellfish should be avoided because of Vibrio vulnificus, a bacteria that can cause potentially fatal infection and that has been reported in patients with high iron levels. Elevated iron stores can impair effective hepcidin bactericidal activity.41 Screening The AASLD, American Academy of Family Physicians, Centers for Disease Control and Prevention, and U.S. Preventive Services Task Force recommend against uni­ versal genetic screening for hereditary hemochroma­ tosis.14,42-44 Disagreement about disease penetrance in genotypically affected persons and racial disparities in disease prevalence argue against general screening.45,46 The Iron Disorders Institute and AASLD recommend targeted screening. All first-degree relatives of persons with hereditary hemochromatosis should be screened.

Children who have one parent with hereditary hemo­ chromatosis should not undergo genetic testing until after the other parent is tested. If the other parent is nor­mal (i.e., absence of C282Y, S65C, or H63D gene defects), all children will be simple heterozygous and will not have an increased risk of iron overload.14,18,20 Hepatocellular carcinoma accounts for approximately 30 percent of deaths in patients with hereditary hemo­ chromatosis. Hepatocellular carcinoma very rarely occurs in patients without cirrhosis, highlighting the importance of early detection and treatment of iron overload (Figure 228). Patients with hereditary hemo­ chromatosis and cirrhosis should have screening ultra­ sonography every six to 12 months. If a lesion smaller than 1 cm is found on the liver, the screening interval

changes to every three to six months. If the lesion is 1 cm or greater, referral to a gastroenterologist is recom­mended for four-phase multidetector computed tomog­raphy and biopsy.47 Early phlebotomy promotes cirrhotic regression and reduces morbidity and mortality.13,48,49 For complete article see www.aafp.org/afp REFERENCES 1. Andrews NC. Disorders of iron metabolism [published correction appears in N Engl J Med. 2000;342(5):364]. N Engl J Med. 1999;341(26):1986-1995.

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44. Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preven­tive Services Task Force. Ann Intern Med. 2006;145(3):209-223.

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46. Rossi E, Olynyk JK, Jeffrey GP. Clinical penetrance of C282Y homozy­gous HFE hemochromatosis. Expert Rev Hematol. 2008;1(2):205-216.

47. Bruix J, Sherman M; American Association for the Study of Liver Dis­eases. Management of hepatocellular carcinoma: an update. Hepatol­ogy. 2011;53(3):1020-1022.

48. Falize L, Guillygomarc’h A, Perrin M, et al. Reversibility of hepatic fibro­sis in treated genetic hemochromatosis: a study of 36 cases. Hepatol­ogy. 2006;44(2):472-477.

49. Adams PC, Speechley M, Kertesz AE. Long-term survival analysis in hereditary hemochromatosis. Gastroenterology.

1991;101(2):368-372.

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American Family Physician

Practice Guidelines AAP Releases Guideline on Managing Type 2 Diabetes Mellitus in Patients 10 to 18 Years of Age Childhood obesity has dramatically increased in North America over the past 30 years, leading to earlier onset of type 2 diabetes mellitus, which previously did not normally occur until later in life. Childhood type 2 diabetes poses a challenge to many physicians who are not used to treating this disease in such young patients.

The American Academy of Pediatrics (AAP) has released a guideline of evidence-based recommendations for treating type 2 diabetes in patients 10 to 18 years of age.

The guideline focuses on treatments that have been shown to affect clinical outcomes in these patients.

Definitions Childhood type 2 diabetes is disease in a child who typically: ÂÂ Is overweight (body mass index in the 85th to 94th

percentile) or obese (body mass index in the 95th percentile or greater)

ÂÂ Has a strong family history of type 2 diabetes ÂÂ Has substantial residual insulin secre­tory capacity

at diagnosis (reflected by normal or elevated insulin and C-peptide concentrations)

ÂÂ Has insidious onset of disease ÂÂ Demonstrates

insulin resistance (includ­ ing clinical evidence of polycystic ovary syndrome or acanthosis nigricans)

ÂÂ Lacks evidence for diabetic autoimmu­nity (negative

for autoantibodies typi­cally associated with type 1 diabetes); these patients are more likely to have hypertension and dyslipidemia than are those with type 1 diabetes

Diabetes is defined as one of the following: ÂÂ A1C level of 6.5% or greater (test per­formed in an

appropriately certified laboratory)

ÂÂ Fasting (no caloric intake for at least eight hours)

plasma glucose level of 126 mg per dL (7.0 mmol per L) or greater

Source: Adapted from Am Fam Physician. 2013;88(10):710-712.

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ÂÂ Two-hour plasma glucose level of 200 mg per dL

(11.1 mmol per L) or greater during an oral glucose tolerance test (using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water)

ÂÂ A random plasma glucose level of 200 mg per dL

or greater with symp­toms of hyperglycemia

Action Statements Clinicians must ensure that insulin therapy is initiated in children and adolescents with ketosis or diabetic ketoacidosis, in whom the distinction between type 1 and 2 diabetes is unclear. Usually, insulin therapy should be initiated in patients with a random venous or plasma blood glucose concentration of 250 mg per dL (13.9 mmol per L) or greater, or an A1C level greater than 9%.

Type 2 diabetes in children and ado­ lescents may present differently depending on disease stage. In early disease, before diagnostic criteria are met, blood glucose concentrations may be normal much of the time and patients may be asymptomatic. At this stage, the disease may be detected only with abnormal blood glucose measurements during screening. As insulin secretions decline, patients will likely begin to have symptoms of hyperglycemia, sometimes with ketosis or frank ketoacidosis.

Diabetic ketoacidosis is treated with insulin and fluid, as well as electrolyte replacement to prevent the disease from worsening. These patients need immediate inpa­ tient therapy under the care of a physician experienced in treating diabetic ketoacidosis.

Children and adolescents who have type 2 diabetes and poor glycemic control, but no evidence of ketosis or ketoacidosis, may also benefit from insulin therapy, at least short term. Initially, it may be difficult to differen­ tiate type 1 and type 2 diabetes. Insulin therapy should be administered while appropriate testing is performed.

Clinicians should initiate a lifestyle modification pro­ gram, including nutrition and physical activity, and start metformin (Glucophage) as first-line therapy at the time of type 2 diabetes diagnosis, unless insulin is needed to reverse glucose toxicity in the case of significant hypergly­cemia or ketoacidosis.

Because the combination of diet and exercise alone has not been highly successful in children and adoles­cents

American Family Physician with type 2 diabetes, lifestyle modifications should be initiated with metformin. Gastrointestinal adverse effects are common at the beginning of metformin therapy; therefore, it should be started at a low dosage of 500 mg daily, and increased by 500 mg every one to two weeks to a maximum of 2,000 mg daily in divided doses. Extended-release metformin may be considered, although data regarding adverse effects are lacking.

In children and adolescents, a multidisciplinary approach to lifestyle modifications with the involvement of the whole family is most successful. Expert consensus is that less than 10% of children and adolescents will maintain lifestyle changes long term. Patients are more likely to succeed if they are treated simultaneously with medications, possibly because they will have a greater degree of concern for their health than if medication is not needed.

In patients with more modest hyperglycemia (e.g., random blood glucose level of 200 to 249 mg per dL [11.1 to 13.8 mmol per L]) or asymptomatic type 2 dia­ betes, metformin alone, insulin alone, or metformin and insulin are reasonable options for initial pharmacologic management.

A1C concentrations should be monitored every three months and treatment intensified if results do not meet the goals for finger-stick blood glucose and A1C concentrations.

The A1C target ideally should be less than 7%. If this seems unattainable for a patient, an individualized goal should be set, with the intention of ultimately meeting the guideline target of less than 7%. In the absence of hypoglycemia, a lower goal can be considered.

If goals are not reached, therapy should be intensified if possible. This may include increasing clinic visits, monitoring blood glucose levels more often, adding one or more antidiabetic agents, consulting a registered dietitian or diabetes educator, and increasing attention to diet and exercise regimens. If A1C concentrations remain relatively stable, testing may be extended to every six months.

Clinicians may advise patients to monitor finger-stick blood glucose concentrations if they are taking insulin or other medications with a risk of hypoglycemia; are starting or changing a diabetes treatment regimen; have not met treatment goals; or have comorbid illnesses.

Although the benefit of frequent blood glucose moni­ toring has not been evaluated in children and ado­ lescents with type 2 diabetes, a fasting blood glucose concentration of 70 to 130 mg per dL (3.9 to 7.2 mmol per L) is a reasonable goal in most adolescents.

Current American Diabetes Association recommen­ dations for finger-stick monitoring may be applied to most children and adolescents with type 2 diabetes: (1) monitoring should be performed at least three times daily for patients using multiple insulin injections or insulin pump therapy; (2) for patients using less fre­ quent insulin injections, noninsulin therapies, or medi­ cal nutrition therapy alone, monitoring may be useful as a guide to the success of therapy; and (3) to achieve postprandial glucose targets, postprandial finger-stick monitoring may be appropriate.

All patients with a new diagnosis should perform finger-stick blood glucose testing before meals (includ­ ing the morning fasting concentration) and at bedtime, regardless of treatment plan. The frequency of testing can be decreased in some patients after the target level is met. Patients and families should receive a written action plan.

In patients using a regimen consisting of a single bedtime insulin injection (basal insulin only), the best way to determine the appropriate dose is by using the morning fasting blood glucose concentration. There­ fore, a daily fasting blood glucose measurement is recommended. Although more labor intensive, basal bolus insulin regimens may be appropriate for children and adolescents with type 2 diabetes. The bolus dose is calculated using a correction algorithm for the pre­ meal blood glucose concentration and a “carb ratio,” in which 1 U of insulin is given for a certain amount of carbohydrates consumed. In addition, more insulin is given when the blood glucose concentration is above the target level. For example, if an adolescent has a blood glucose con­centration of 250 mg per dL, will eat a meal containing 60 g of carbohydrates, with a carb ratio of 1:10 (1 U of insulin for every 10 g of carbohydrates) and an assigned correction dose of 1:25 > 125 (1 U of insulin for every 25 mg per dL that the glucose level is above the target of 125 mg per dL), the mealtime bolus dose of insulin would be as follows: 60 g/10 carb ratio = 6 U rapid-acting insulin for the meal plus (250 - 125)/25 = 125/25 = 5 U rapid-acting insulin for correction Thus, the total bolus insulin coverage at mealtime would be: 11 U (6 + 5) of rapid-acting insulin.

Clinicians may incorporate the Academy of Nutrition and Dietetics’ Pediatric Weight Management Evidence-Based Nutrition Practice Guidelines in their counseling of patients with type 2 diabetes, at the time of diagnosis and as part of ongoing management.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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American Family Physician Patients should be referred to a registered dietitian with expertise in the nutritional needs of children and adolescents with type 2 diabetes and advised to follow guidelines from the Academy of Nutrition and Dietetics. These recommendations include a balanced macronutri­ent diet with lifestyle modifications, nutritional coun­seling, and caregiver participation.

Clinicians may encourage patients to participate in adequate exercise and limit screen time.

Children and adolescents with type 2 diabetes should participate in moderate to vigorous exercise for at least 60 minutes daily. This may be completed in several, shorter increments (e.g., 10 to 15 minutes) throughout the day. A written exercise prescription that takes into account the patient’s physical abilities, preferences, and circumstances may increase adherence. Medication dos­ ages may need to be adjusted when initiating an aggres­ sive physical activity program. Nonacademic screen time should be limited to less than two hours a day.

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Promising Medical Advances Insights into brain injury A study by NIH researchers provided insight into the damage caused by mild traumatic brain injury and suggested approaches for reducing its harmful effects.

Stem cells coaxed to create working blood vessels In an NIH–funded study, scientists were able to direct human stem cells to form networks of tiny blood vessels that can connect to the existing circulation in mice Genomic analysis of endometrial tumors The findings, by an NIH–funded research network, suggest that genomic classification of endometrial tumors could help guide treatment strategies.

Common genetic factors found in 5 mental disorders Autism, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depression, and schizophrenia were traditionally thought of as distinct mental disorders. An international research consortium funded by NIH discovered that these disorders share certain genetic glitches.

Vaccine clears away monkey AIDS virus Current therapies can control but not eliminate the virus. In an NIH–funded study, an experimental vaccine triggered a lasting immune attack in monkeys that eliminated all traces of HIV infection after a year or more.

Method quickly assesses antibiotics NIH–funded scientists developed an innovative method to quickly identify antibiotics that can treat multidrug– resistant bacteria—and reveal how these bacteria–killing medications work.

Strategy may improve survival after shock An NIH–funded study of rats found that blocking digestive enzymes in intestines increases survival, reduces organ damage, and improves recovery after shock. The approach may lead to new therapies to improve patient outcomes.

Source: emedinews Dec 28, 2013

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

American Family Physician

Photo Quiz Painful Red Eye A 46-year-old man presented to the emer­ gency department with unilateral pain in his left eye that began one day earlier. He had redness and a foreign body sensation. There were no vision changes, discharge, trauma, or recent upper respiratory tract symptoms.

On examination, his pupils were reactive to light with normal ocular motor function. He had consensual photophobia. Slit lamp examination showed ciliary flush and cell flaring, but no conjunctival injection. The patient was further evaluated with fluores­cein staining (Figure 1).

Question Based on the patient’s history, physical examination, and microscopy findings, which one of the following is the most likely diagnosis?

Figure 1.

A. Foreign body.

B. Fungal keratitis.

C. Herpes keratitis.

D. Sarcoidosis.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2013;87(2):127‒128.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

723

American Family Physician Discussion The answer is C: herpes keratitis.

Herpes simplex virus is one of the leading causes of infectious keratitis resulting in blindness. Herpes keratitis is the most common ocular form of herpes infection and usually presents as an infection of the superficial epithelium with dendritic lesions in this toms of herpes keratitis vary but may layer.1 Symp­ include pain, blurred vision, sensitivity to light, red eye, watery discharge, or foreign body sensa­tion. Recurrent episodes are common.

The diagnosis is made based on history and slit lamp examination.1 This patient’s examination with

Figure 2. Slit lamp examination with fluores­cein staining shows a dendritic lesion (arrow) in a patient with herpes keratitis.

Summary Table Condition

Examination findings

Characteristics

Foreign body

Foreign body in anterior or posterior chamber; corneal epithelial injury/defect

Excruciating pain, tearing, scratchy sensation with blinking

Fungal keratitis

Dry, gray, elevated infiltrate, and satellite lesions

History of trauma with vegetative matter, or long-term steroid use; pain, red eye, foreign body sensation, or discharge

Herpes keratitis

Dendritic lesions in the epithelial layer

Pain, blurred vision, sensitivity to light, red eye, foreign body sensation, or watery discharge

Uveitis from sarcoidosis

Redness in corneal area, decreased visual acuity

Bilateral ocular pain and photophobia; granuloma formation in the conjunctiva and uvea

fluorescein staining revealed a dendritic lesion (Figure 2). Labo­ratory testing is generally not indicated.

Herpes keratitis is treated with antiviral therapy.2 Patients with a foreign body may have excruciating pain, tearing, and a scratchy sensation with blinking.

Slit lamp examina­tion may reveal a foreign body in the anterior or posterior chamber. However, if the object is not present, fluorescein staining may dem­onstrate a corneal epithelial injury or defect.1 Patients with fungal keratitis may have a history of trauma with vegetative mat­ter, or long-term steroid use.1,3 Common symptoms include pain, red eye, foreign body sensation, and discharge. Typical slit light examination findings include a dry, gray, elevated infiltrate and satellite lesions. Diagnosis requires laboratory confirmation using a fungal culture.

Ocular sarcoidosis can manifest before the presentation of systemic sarcoidosis. Uveitis is a common ocular

manifestation of sar­ coidosis.4 Examination shows redness in the corneal area. Patients present with bilateral ocular pain, photophobia, and decreased vision, and granuloma formation can be seen in the conjunctiva and uvea.

REFERENCES 1. Kunimoto DY, Kanitkar KD, Makar M; Wills Eye Hospi­ tal. The Wills Eye Manual. Office and Emergency Room Diagnosis and Treatment of Eye Disease. 5th ed. Phila­ delphia, Pa.: Lippincott Williams & Wilkins; 2008.

2. Guess S, Stone DU, Chodosh J. Evidence-based treat­ment of herpes simplex virus keratitis: a systematic review.

Ocul Surf. 2007;5(3):240-250.

3. Thomas PA. Fungal infections of the cornea. Eye (Lon­ don). 2003;17(8):852-862.

4. Heiligenhaus A, Wefelmeyer D, Wefelmeyer E, Rösel M, Schrenk M. The eye as a common site for the early clinical manifestation of sarcoidosis. Ophthalmic Res. 2011;46(1):9-12.

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CARDIOLOGY

Comparative Evaluation of Angiotensin-Converting Enzyme Inhibitors for their Beneficial Effects in Patients with Ischemic LV Systolic Dysfunction and Undergoing Coronary-Artery Bypass Surgery PS Gandhi*, RK Goyal†, AR Jain ‡, BS Mallya‡, MC Chag‡, VM Gupta‡, DS Shah‡, BR Trivedi‡, NA Shastri‡, CB Mehta‡, KA Jain‡, NS Bhavasar‡, UJ Shah‡

Abstract We compared three angiotensin-converting enzyme (ACE) inhibitors, captopril, perindopril, and ramipril, in the presented prospective study for their effectiveness in patients having left ventricular (LV) systolic dysfunction and undergoing coronaryartery bypass grafting (CABG). We enrolled 27 patients in captopril, 43 patients in perindopril, and 70 patients in ramipril group. There was about 25%–36% rise in LVEF after 3 and 6 months of ACE inhibitor administration in all three groups.

The reduction in LV diameters did not differ significantly amongst the three groups. There was a significant decrease (p < 0.05) in LV end-diastolic diameter from baseline levels in captopril and perindopril groups after 3 months that got increased after 6 months but remained below pretreatment levels in both the groups. In ramipril group, there was no much change in this parameter from baseline levels at 3 and 6 months of treatment. After 6 months of treatment, the percent reduction in LV end-systolic diameter was also sustained in perindopril-treated patients. The percent reduction was greater in the perindopril group (3 and 6 months: 7.39 ± 5.94 and 7.73 ± 3.43, respectively) as compared to that observed in captopril group (3 and 6 months: 5.67 ± 1.05 and 2.52 ± 3.11, respectively) and ramipril group (3 and 6 months: 7.30 ± 2.75 and 4.93 ± 3.22, respectively).

Mitral-valve regurgitation was greatly reduced in the captopril group at 3 as well 6 months of ACE inhibitor administration.

However, the percent reduction from baseline levels was not statistically significant amongst the three groups. The percent improvement in functional status was significantly greater in the ramipril treatment group (36.46 ± 3.14) after 6 months of treatment as compared to that of captopril (6.67 ± 10.64) and perindopril (4.17 ± 2.73) group. In conclusion, our data show equal beneficial effects with all three ACE inhibitors under investigation in CABG patients with LV systolic dysfunction, with marginal superiority for perindopril.

Keywords: Captopril, perindopril, ramipril, left ventricular, systolic dysfunction, coronary-artery bypass grafting

A

bout 23 million people worldwide are afflicted with heart failure (HF) and 2 million new cases of HF are diagnosed each year worldwide.1 As per the Heart and Stroke Statistics Update of American Heart Association, nearly 5 millions in the United States suffer from HF.2 A large survey, namely, MONICA survey, found that the prevalence of left ventricular (LV) dysfunction in Britain was 2.27%.3

*Associate Professor Dept. of Pharmacology, Shree Dhanvantary Pharmacy College, Kim, Surat †Professor, Institute of Life Sciences, Ahmedabad University, Ahmedabad ‡The Heart Care Clinic, Ahmedabad Address for correspondence Dr Purvi S Gandhi Dept. of Pharmacology Shree Dhanvantary Pharmacy College Near Railway Station, Kim (E), Surat - 394 110, Gujarat E-mail: psgandhi1975@gmail.com

Indians and other South Asians are more likely to die from HF in comparison to Caucasians.4 The incidence of HF is on rise in the past few decades.1 Since myocardial infarction (MI) or severe ischemia, resulting from multiple-vessel coronary artery disease (CAD), is the main underlying cause in the LV systolic dysfunction, surgical revascularization of diseased coronary arteries by coronary-artery bypass grafting (CABG) is one of the common interventions for the treatment of such patient population.5 However, postsurgical therapy with pharmacological measures is needed to sustain the beneficial effects of the former.6 Involvement of neurohormonal system especially sympathetic system and renin–angiotensin–aldosterone system (RAAS) in LV remodeling through direct as well as indirect mechanism is well documented.7,8 Several angiotensinconverting enzyme (ACE) inhibitors and antagonists

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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CARDIOLOGY of angiotensin-II receptor subtype-1 (AT1) have shown a significant reduction in mortality and morbidity in patients having LV systolic dysfunction.9-14 Longterm treatment with ACE inhibitors produces absolute increases in LVEF.15 Captopril has been found to reverse ventricular dilation caused by MI.16 Enalapril has also been reported to reverse progression of LV dilation in patients with asymptomatic systolic dysfunction.17 Thus, many clinical trials and researches are available showing beneficial effects of various ACE inhibitors; American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines recommend ACE inhibitors for treatment of LV systolic dysfunction, if not contraindicated.18 Majority of the reports on beneficial effects of ACE inhibitors in patients with LV dysfunction include placebo-controlled research and do not compare various ACE inhibitors in a single research for their beneficial effects on such patient population.10,19,20 In our earlier report, we found captopril and perindopril more efficient in improving LV contractility as compared to ramipril, lisinopril, and losartan.21 Captopril and perindopril produced a significant increase in percent LVEF as compared to other ACE inhibitors and losartan. Perindopril also decreased insulin levels significantly. There was a significant correlation between decreases in blood glucose as well as insulin levels with improvements in LVEF.21 However, the evidence was based on assessment of biochemical parameters to correlate the improvements in LVEF produced by these drugs, while the clinical parameter included echocardiographic evaluation. Hence, we compared various ACE inhibitors in one research for their beneficial effects on patients having ischemic LV systolic dysfunction and undergoing CABG using echocardiographic parameters.

Methods The study presented here includes the research carried out at SAL Hospital and Sterling Hospital, Ahmedabad, Gujarat. The research was approved by the Ethics Committee of both the hospitals. Written informed consent was taken from all the patients who were eligible for the investigation. Moreover, all patients were explained about the procedures, the risks and the benefits of the interventions.

Study Design It was a prospective, randomized, open-label research.

The research did not include control group since ACE

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

inhibitors have proven absolute beneficial effects on patients with LV systolic dysfunction. Furthermore, as per the ACC/AHA guidelines for management of HF, all the patients with LV systolic dysfunction should be treated with ACE inhibitor if there is no contraindication. Therefore, the control group was not included and comparison among the three ACE inhibitors was carried out.

Patient Selection Inclusion Criteria Patients presented with ischemic LV systolic dysfunction [defined as LVEF ≤ 30% as revealed from two-dimensional (2D) echocardiography] and undergoing CABG were included.

Exclusion Criteria Patients of age above 70 years, previous or recent history of second or third-degree atrioventricular block,

Clinical Flowchart Patient’s Hospitalization for CABG Assessment for biographic, clinical, and biochemical characteristics as well as 2D echocardiography and color Doppler parameters Enrollment of patient, meeting selection criteria, in research, randomization, patient’s counseling, and collection of patient’s informed consent Stabilization of patient for 1-2 days depending upon the hemodynamic status Conduct of CABG by surgeons followed by observation - under intensive care unit for 1-1.5 days and in ward for 3-5 days for any major adverse cardiac event (MACE) or mortality Drug and dose setting during postsurgery in-hospital stay Discharge of patient from hospital on stabilization of hemodynamic status; patient’s counseling about medication and general measures to be taken by the patient and follow-up at the time of discharge Assessment of clinical characteristics, 2D echocardiography and color Doppler parameters at 1, 3, and 6 months of surgery and drug administration, and mortality and MACE recording up to 6 months Data compilation and analysis performed using Microsoft Windows XP and GPower (Version 2, by Franz Faul & Edgar Erdfelder, Germany).

(Source: Stat CD, Indian J Pharmacol, 2004).

CARDIOLOGY renal failure (serum creatinine > 2.6 mg%), hepatic dysfunction [serum glutamate pyruvate transaminase (SGPT) > 45 IU/L), cerebrovascular events, previous history of revascularization, or valve replacement surgery were excluded from the study.

Groups of Patients Patients meeting the selection criteria were randomized into three groups. Group I included patients receiving captopril after CABG. Group II included patients receiving perindopril treatment. In Group III, ramipril was the ACE inhibitor. Patients were evaluated at the time of enrollment a day or two before CABG and were reevaluated at 1, 3, and 6 months of CABG and ACE inhibitor administration. We enrolled 27 patients in Group I, 43 patients in Group II, and 70 patients in Group III.

Treatments As per the strategy, the drug dose regimen was started with the minimum dose of the drug and allowed to attain the maximum dose. Serial dose titration was carried out depending upon the hemodynamic status of the patients. For captopril, the initial dose was 37.5 mg/day that reached up to maximum of 75 mg/day.

Perindopril treatment began with the dose of 2 mg/day and reached maximum dose of 4 mg/ day. Ramipril administration was started with 2.5 mg/day and the highest dose attained was 20 mg/day. In addition to ACE inhibitor, patients were also receiving other drugs, such as diuretic(s), beta (b)-adrenoceptor blocker, and digoxin, that directly was affecting cardiac function. Other drugs that were used included amiodarone, isosorbide dinitrate, acetylsalicylic acid, and statin, depending upon the requirements. Patients were also advised of general measures about lifestyle modifications, that is, cessation of smoking, tobacco chewing, or alcoholism, regular exercise of lowmedium caliber, and restricted total salt intake and fluid intake (2–3 L/day) as well as fat intake.

Biographic Characteristic Assessment Patient’s biographic characteristics, that is, age and associated risk factors, such as habit of smoking, tobacco chewing, or alcoholism, and family history of ischemic heart disease (IHD) were noted by questioning at the time of enrolment. Body weight was measured with the help of pedal weighing balance. Patient’s height was measured in patient’s standing position using vertical height-measuring column device.

Clinical Assessment Clinical assessment included patient’s hemodynamic parameters, that is, pulse rate and systolic and diastolic blood pressure measured in patient’s seating position with elbow at the level of heart using sphygmomanometer. They were evaluated for electrocardiogram and CAD characteristics using coronary angiography pattern carried out preoperatively. Functional capacity was determined as per New York Heart Association (NYHA) class for HF, assigning patients to one of four functional classes depending upon the degree of effort needed to elicit symptoms.22

2D Echocardiography and Color Doppler Assessment Two-dimensional echocardiography and color Doppler assessment was performed using Caris Plus (Esaote, USA) machine by the cardiologist who was unaware of the treatment given. Recommendations of the American Society of Echocardiography were followed by the cardiologist for measuring various parameters. Images were obtained from a patient lying on the left side in a supine position with the body elevated at about 30°. LVEF was assessed using standard parasternal and apical views. LV end-diastolic diameter (LVEDd) and LV end-systolic diameter (LVEDs) were measured using four-chamber and two-chamber views with apical approach at the level of papillary muscle. Severity of mitral-valve regurgitation (MR) was found out using color Doppler assessment. LVEF, LVEDd, LVEDs, and MR-grade were measured a day or two before and 1, 3, and 6 months following CABG and ACE inhibitor administration. Mortality and MACE was noted up to 6 months of drug treatment under consideration.

Biochemical Parameter Assessment Blood samples from patients were collected at the time of enrollment for biochemical parameters testing that was done in in-hospital pathology laboratory following good laboratory practices. Biochemical parameters assessed included serum glucose, serum urea, serum creatinine, SGPT, serum total cholesterol, serum triglyceride and serum high-density lipoprotein (HDL) cholesterol, serum low-density lipoprotein (LDL) cholesterol, serum potassium (K+), and serum sodium (Na+).

Data Analysis The data were analyzed by finding mean ± standard error of mean for numerical and ordinal data while

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CARDIOLOGY Table 1. Baseline Biographic Characteristics of Patients Parameter

Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

27 (100%)†

38 (88.37%)

67 (95.71%)

Age

(years)*

57.14 ± 1.84

60.25 ± 1.34

56.89 ± 1.07

BMI

(kg/m2)*

26.36 ± 1.53

27.48 ± 1.13

25.31 ± 1.32

Sex Males (%)

Lifestyle (stress) Heavy

9 (33.33%)

3 (6.98%)

14 (20.0%)

Moderate

7 (25.92%)

15 (34.88%)

16 (22.86%)

Sedentary

11 (40.74%)

25 (58.14%)

40 (57.14%)

Symptoms Dyspnea on exertion Edema Chest pain

16 (59.26%)

23 (53.49%)

2 (7.40%)

4 (9.30%)

15 (55.55%)

22 (51.16%)

29 (41.43%) 2 (2.86%) 45 (64.29%)

BMI = body mass index; kg/m2 = kilogram per square meter. *Mean ± SEM. †Values

in brackets are percent of total n in each group.

percent of number (n) of patients for nominal data.

Chi-square test was used to find difference of statistical significance in categorical measurements among the three groups. For parametric numerical data, results were obtained by applying Student’s t test to find the change in characteristics from baseline levels. Analysis

of variance (ANOVA) was used for numerical data to find the significant difference among the three treatment groups. Difference among the groups, and hence treatment, was considered statistically significant if “p” value was found to be less than 0.05 (p < 0.05). Post hoc power analysis was done using GPower software. The

Table 2. Prevalence of Risk Factors in Patients at the Time of Enrolment Risk Factor

Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

Habit Alcoholism Smoking

1 (3.7%)*

0 (0%)

4 (5.71%)

5 (18.52%)

5 (11.63%)

18 (25.71%)

1 (3.7%)

6 (13.95%)

17 (24.28%)

DM

10 (37.03%)

21 (48.83%)

36 (51.43%)

HT

7 (25.92%)

17 (39.53%)

29 (41.43%)

DM + HT

3 (11.11%)

10 (23.26%)

17 (24.29%)

IHD

7 (25.93%)

8 (18.6%)

24 (34.28%)

Past history of MI

18 (66.67%)

21 (48.84%)

42 (60.0%)

Tobacco chewing Disease

Positive family history

DM = diabetes mellitus; HT = hypertension; IHD = ischemic heart disease; MI = myocardial infarction. *Values in brackets are percent of total n in each group.

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CARDIOLOGY Table 3. Biochemical Parameters at Baseline Level Biochemical Parameter

Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

155.59 ± 10.82

149.01 ± 12.43

176.79 ± 7.55

29.59 ± 1.43

32.23 ± 1.39

34.34 ± 1.16

1.18 ± 0.08

1.19 ± 0.03

1.15 ± 0.03

SGPT (IU/L)*

28.58 ± 2.52

30.37 ± 1.51

33.4 ± 1.23

Serum K+ (mEq/L)*

4.47 ± 0.07

4.10 ± 0.08

4.32 ± 0.07

Serum Na+ (mEq/L)*

135.98 ± 1.47

135.89 ± 0.81

136.56 ± 0.54

Serum T-Chol (mg%)*

112.0 ± 8.54

110.45 ± 4.59

117.65 ± 3.61

RBS (mg%)* Serum urea

(mg%)*

Serum creatinine

Serum TG

(mg%)*

(mg%)*

75.68 ± 6.46

99.53 ± 8.14

106.17 ± 7.49

Serum LDL-Chol

(mg%)*

59.87 ± 6.55

54.56 ± 4.38

61.61 ± 2.96

Serum HDL-Chol

(mg%)*

31.53 ± 1.52

27.96 ± 1.79

27.71 ± 1.22

HDL-Chol = high-density lipoprotein-cholesterol; IU = international unit; K+, potassium; LDL-Chol = low-density lipoprotein-cholesterol; mEq = milliequivalence; mg, milligram; Na+ = sodium; RBS = random blood sugar; SGPT = serum glutamate pyruvate transaminase; T-Chol = total cholesterol; TG = triglyceride. *Mean ± SEM.

power of the study (1 - b) has been presented along with the respective level of significance.

Results Baseline biographic characteristics, risk factor association, and biochemical variables were similar

among the three groups (Tables 1-3). There was no significant (p < 0.05) difference in CAD characteristics, medication affecting cardiac function other than ACE inhibitors, hemodynamics (such as heart rate, systolic and diastolic blood pressure), and baseline 2D echocardiography characteristics among the three groups (Tables 4-7). After 1, 3, and 6 months

Table 4. Angiographic Pattern of Stenosed Coronary Arteries as Revealed by Angiography Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

Single-vessel disease

0 (0%)*

1 (2.32%)

0 (0%)

Double-vessel disease

4 (14.81%)

7 (16.28%)

8 (11.42%)

Triple-vessel disease

23 (85.18%)

35 (81.39%)

62 (88.57%)

2 (7.41%)

8 (18.60%)

10 (14.23%)

2 (7.41%)

7 (16.28%)

10 (14.23%)

LAD (100%)

17 (62.96%)

7 (39.53%)

30 (42.86%)

LAD (70%-99%)

6 (22.22%)

20 (46.51%)

36 (51.43%)

LCx (100%)

3 (11.11%)

9 (20.93%)

7 (10.0%)

LCx (70%-99%)

8 (29.63%)

16 (37.21%)

29 (41.43%)

RCA (100%)

9 (33.33%)

17 (39.53%)

28 (40.0%)

RCA (70%-99%)

11 (40.74%)

13 (30.23%)

31 (44.29%)

Diffusely diseased artery

Diseased artery, lesion severity, that is, percent blockade of diameter LMCA (≥50%)

LMCA = left main coronary artery; LAD = left anterior descending artery; LCx = left circumflex artery; RCA = right coronary artery. *Values in brackets are percent of total n in each group.

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CARDIOLOGY Table 5. Medication Affecting Cardiac Function Other than ACE Inhibitors Given to Patients Following CABG Medication

Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

Digoxin

23 (85.18%)*

29 (67.44%)

49 (70.0%)

Diuretics

25 (92.59%)

37 (86.04%)

62 (88.57%)

β-adrenoceptor blocker

15 (55.55%)

17 (39.53%)

33 (47.14%)

ACE = angiotensin-converting enzyme; CABG = coronary-artery bypass grafting. *Values in brackets are percent of total n in each group.

Table 6. Hemodynamic Levels in Patients at Baseline (at the Time of Enrolment) and at 1, 3, and 6 Months of Treatment Parameters

Group I (Captopril) (n = 27)

Group II (Perindopril) (n = 43)

Group III (Ramipril) (n = 70)

Baseline

79.60 ± 1.42

85.72 ± 2.49

82.71 ± 2.13

1 month

83.0 ± 1.34

83.92 ± 0.84

83.85 ± 0.99

3 months

81.0 ± 2.45

79.0 ± 1.32

82.4 ± 1.24

6 months

84.0 ± 1.62

82.0 ± 1.12

86.67 ± 1.56

Baseline

125.4 ± 3.69

122.89 ± 2.82

123.75 ± 2.10

1 month

119.0 ± 1.98

125.81 ± 2.74

119.84 ± 1.44

3 months

121.0 ± 3.17

125.67 ± 4.11

127.0 ± 2.86

6 months

126.25 ± 2.45

126.78 ± 3.24

122.0 ± 1.59

Baseline

76.24 ± 1.42

78.19 ± 1.58

79.75 ± 1.16

1 month

76.18 ± 1.59

80.84 ± 1.08

78.01 ± 0.90

3 months

83.0 ± 4.62

83.33 ± 0.83

80.8 ± 1.34

6 months

81.34 ± 2.56

80.0 ± 1.27

83.33 ± 0.70

HR (beats/min)*

SBP

DBP

(mmHg)*

(mmHg)*

DBP = diastolic blood pressure; HR = heart rate; mmHg = millimeters of mercury; SBP = systolic blood pressure. *Mean ± SEM.

of ACE inhibitor administration following CABG, 2D echocardiography showed a significant (p < 0.05) improvement in LV contractility from baseline levels (i.e., levels at the time of enrollment) in captopril and ramipril groups. In perindopril treatment group, the increase in LVEF was found to be statistically significant after 1 and 3 months of treatment. Increase in LVEF in terms of percent change from baseline levels in individual patients did not differ significantly among the three groups; however, the increase was greater and persistent in perindopril group (Table 7 and Fig. 1).

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

There was a significant decrease in LVEDd from baseline levels in captopril and perindopril groups after 3 months that increased after 6 months but remained below pretreatment levels in both the groups. In ramipril group, no much change in this parameter was observed from baseline levels after 3 and 6 months of treatment (Table 7 and Fig. 2). After 3 months of treatment, LVEDs was significantly decreased in captopril and perindopril groups as compared with baseline levels. However, after 6 months, there was an increase in this parameter in both the groups. In ramipril-treated patients, no significant decrease in LVEDs was observed after

CARDIOLOGY Table 7. 2D Echocardiography and Color Doppler Characteristics and NYHA Class for HF in Patients at the Time of Enrolment (Baseline) and at 1, 3, and 6 Months of ACE Inhibitor Treatment Parameters 2D echocardiography and color Doppler:

Group I (Captopril) n = 27

% change from baseline in individual patients

Group II (Perindopril)

Group III (Ramipril)

n = 70 % change from baseline in individual patients

n = 43

% change from baseline in individual patients

LVEF (%)* Baseline 1 month 3 months 6 months

25.89 ± 0.84 31.68 ±

1.95‡

33.25 ±

2.36‡

36.25 ±

2.51‡

24.91 ± 1.07 30.38 ± 7.23 26.11 ± 7.22 39.42 ± 9.49

29.44 ±

2.65‡

35.43 ±

2.60‡

28.5 ± 3.42

25.21 ± 0.57 26.12 ± 6.44

30.29 ± 1.14‡

17.74 ± 5.09

36.61 ± 7.68

32.59 ±

1.49‡

35.28 ± 6.72

33.03 ±

1.58‡

25.61 ± 6.34

39.2 ± 7.92

LVEDd (mm)* Baseline

55.86 ± 1.60

1 month

52.18 ± 2.80 2.03‡

3 months

50.5 ±

6 months

53.98 ± 1.47

57.25 ± 1.23 7.67 ± 3.99 6.3 ± 3.84 -2.55 ± 2.07

58.56 ± 2.06 53.83 ±

2.01‡

54.93 ± 2.65

54.82 ± 0.90 10.97 ± 9.49

52.28 ± 1.53

-1.9 ± 2.81

3.18 ± 3.86

55.39 ± 1.96

2.99 ± 1.32

4.81 ± 1.16

54.14 ± 1.07

2.87 ± 2.05

LVEDs (mm)* Baseline

44.17 ± 1.57

1 month

41.35 ± 2.72

44.37 ± 1.40 6.37 ± 4.85

3 months

38.28 ±

2.31‡

5.67 ± 1.05

6 months

39.91 ± 1.28‡

2.52 ± 3.11

47.02 ± 2.32 38.18 ±

1.86‡

44.3 ± 2.87

43.18 ± 1.07 -2.62 ± 4.36

39.93 ± 1.64

-0.7 ± 4.01

7.39 ± 5.94

41.83 ± 2.00

7.30 ± 2.75

7.73 ± 3.43

40.28 ± 1.37

4.93 ± 3.22

MR-grade* 0.46 ± 0.08†

Baseline

0.77 ± 0.11

0.7 ± 0.08

1 month

0.82 ± 0.1

-24.55 ± 38.41

0.49 ± 0.16

41.67 ± 13.14 0.6 ± 0.16

-77.14 ± 58.04

3 months

0.6 ± 0.15

50.0 ± 13.87

0.36 ± 0.12

-2.22 ± 41.87 0.7 ± 0.11

-48.75 ± 53.27

6 months

0.5 ± 0.16

50.0 ± 17.41

0.73 ± 0.2

-68.0 ± 53.4

-89.09 ± 64.3

0.68 ± 0.12

NYHA class for HF* Baseline

2.91 ± 0.18 0.22‡

2.94 ± 0.15 5.0 ± 13.41

1.89 ±

3.0 ± 0.15

0.26‡

1 month

2.18 ±

3 months

2.0 ± 0.17‡

34.72 ± 13.14 1.95 ± 0.14‡

6 months

2.67 ± 0.16

6.67 ± 10.64

2.43 ± 0.20‡

25.0 ± 10.8

2.0 ± 0.24‡

28.7 ± 6.07

27.45 ± 4.89

2.17 ± 0.15‡

17.86 ± 5.65

4.17 ± 2.73

2.25 ± 0.15‡

36.46 ± 3.14†

2D = two-dimensional; HF = heart failure; LVEDd = left ventricular end-diastolic diameter; LVEDs = left ventricular end-systolic diameter; LVEF = left ventricular ejection fraction; MR = mitral-valve regurgitation; NYHA = New York Heart Association. *Mean SEM. †Significantly

different as compared with other two groups (p < 0.05).

‡Significantly

different from baseline (p < 0.05).

3 months as well as 6 months of treatment. Decrease in LVEDs in terms of percent change from baseline levels did not differ significantly among the three groups; however, it was more persistent in perindopril

group (Table 7 and Fig. 3). MR-grade did not differ significantly from baseline levels within the groups as well as among the three groups after 3 and 6 months of ACE inhibitor administration. At 6 months of ACE

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735

CARDIOLOGY inhibitor administration, the percent improvement in MR-grade was greatest in captopril group as compared to that produced in perindopril and ramipril groups (Table 7 and Fig. 4). New York Heart Association class was significantly reduced (p < 0.05) from baseline levels in all the three groups after 3 and 6 months suggesting significant improvement in functional status in all the three groups (Fig. 5). Furthermore, in ramipril group, the percent improvement in NYHA class was statistically significant as compared to those observed in the other two groups. Two patients died in ramipril treatment group during posthospital course, one because of sudden fall in heart rate and the other because of recurrent MI. In remaining patients, no MACE was found in all the three groups during 6-month follow-up.

Discussion Hyperactivated neurohormonal systems responsible for the cardinal effects in patients with LV dysfunction mainly include RAAS and sympathetic system. Among various drugs therapy, inhibitors of RAAS are at the top of the recommendations. Various components of RAAS play a significant role in the development of LV remodeling and, thence, in further deterioration of LV dysfunction caused by ischemia and/or infarction.

Thus, suppression of these components has potentialabsolute and synergistic in sustaining the beneficial effects brought about by surgical revascularization.

It is recommended that all HF patients with established LV systolic dysfunction should be treated with ACE inhibitor, until there are contraindications to these agents.18 By inhibiting ACE-systemic and tissue as well, ACE inhibitors reduce afterload and systolic stress too.23,24 These subsequently increase stroke volume due to facilitated stroke work.24,25 By improving renal hemodynamics and by reducing aldosterone secretion, ACE inhibitors prevent blood volume overload.

Consequently, preload and diastolic wall stresses are diminished.26 However, different ACE inhibitors may vary in their activity and thus superiority.

Pfeffer et al10 found captopril treatment (at about 3.5 years of captopril administration) to be more beneficial, as compared with placebo, in patients having LV dysfunction after an MI.10 They found captopril to significantly reduce mortality from cardiovascular cause with 21% risk reduction and also the incidence of major cardiovascular events, defined in terms of development of severe HF (37% reduction), congestive HF (CHF) requiring hospitalization (22% reduction) and recurrent MI (25% reduction). In European trial on reduction

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

of cardiac events with perindopril in stable CAD (EUROPA), perindopril was compared with placebo in patients with stable CAD.20 At average follow-up of 4 years, perindopril was found to produce a 20% relative risk reduction in primary end points, namely, cardiovascular death, MI, or cardiac arrest.20 The Heart Outcomes Prevention Evaluation Study (HOPE) trial reported that ramipril, when compared with placebo at 5 years of administration, significantly reduced the incidences of MI (relative risk 0.8), stroke (relative risk 0.68), or death from cardiovascular causes (relative risk 0.74).19 In this trial, the patient group included those having vascular diseases or diabetes plus another cardiovascular risk factor but low EF or HF.19 Thus, various large randomized placebo-controlled clinical trials have shown the absolute beneficial effects of chronic administration of ACE inhibitors on mortality and major cardiovascular events in patients having CAD with or without LV dysfunction.27,28 Captopril, as compared with enalapril in patients with acute MI (AMI), is comparable in terms of improving LV function and survival.29 Ramipril and captopril are also similar for their effects on serum creatinine, serum K+, cardiac events such as arrhythmias and mortality, as well as in patients with CHF, although ramipril significantly controls the blood pressure with longer duration of action.30 Three-month treatments with captopril and perindopril have been reported to produce similar effects on heart rate, systolic function, and LV mass, although less number of patients in perindopril group as compared with captopril group required add-on therapy with thiazide to normalize the blood pressure.31 Chu-Pak et al32 reported no difference in mortality rates after 6 months of treatment with captopril and perindopril in patients with AMI, although perindopril treatment showed better shortterm tolerance than captopril treatment did, with significantly less acute hemodynamic changes and fewer withdrawals.32 Pilote et al33 found a possible 10%-15% increase in mortality with captopril and enalapril compared with ramipril among patients with CHF.33 However, following adjustment for differences in used dosages, all ACE inhibitors had similar clinical efficacy administered in patients after MI.34 Thus, ours is probably the only research that has compared, in one subset of patient population, the effects of captopril, perindopril, and ramipril in patients with LV systolic dysfunction and that is in patients undergoing CABG. We found an improvement in LV contractility in all the three groups treated with different ACE inhibitors.

There was an increase in LVEF at 1, 3, and 6 months of

CARDIOLOGY 50 45 35

**

*

30

* *

*

**

25 20 15 10 5 0

Baseline 1 month 3 months 6 months

*

MR-grade

LVEF (%)

40

70 60 50 40 30 20 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160

Baseline 1 month 3 months 6 months

Captopril Perindopril Ramipril Captopril Perindopril Ramipril (n = 27) (n = 43) (n = 70) (% change) (% change) (% change)

Figure 1. Effect of ACE inhibitors on LV contractility measured as LVEF in patients with LV systolic dysfunction and undergoing CABG. *Significantly different from baseline (p < 0.05). Power (1 − β) =0.546 at α = 0.4.

Captopril Perindopril Ramipril Captopril Perindopril Ramipril (n = 27) (n = 43) (n = 70) (% change) (% change) (% change)

Figure 4. Effect of ACE inhibitors on MR in patients with LV systolic dysfunction and undergoing CABG. *Significantly different from other groups (p < 0.05).

*

*

Baseline 1 month 3 months 6 months

Captopril Perindopril Ramipril Captopril Perindopril Ramipril (n = 27) (n = 43) (n = 70) (% change) (% change) (% change)

*Significantly different from baseline (p < 0.05).

50

LVEDs (mm)

**

*

30

45

*

40 35 30

Baseline 1 month 3 months 6 months

25 20 15 10 5

††

†††

†††

0

Figure 2. Effect of ACE inhibitors on LVEDd in patients with LV systolic dysfunction and undergoing CABG.

40

50

NYHA class for HF

LVEDd (mm)

65 60 55 50 45 40 35 30 25 20 15 10 5 0 -5 -10

Baseline 1 month 3 months 6 months

20 10 0

-10 Captopril Perindopril Ramipril Captopril Perindopril Ramipril (n = 27) (n = 43) (n = 70) (% change) (% change) (% change)

Figure 3. Effect of ACE inhibitors on LVEDs in patients with LV systolic dysfunction and undergoing CABG. *Significantly different from baseline (p < 0.05).

ACE inhibitor administration. The beneficial effects on LV performance observed after 1 month of CABG may be mainly due to revascularization.35 It is possible that at 3 and 6 months, the observed improvements may be an influence of ACE inhibitor. In the present research,

Captopril Perindopril Ramipril Captopril Perindopril Ramipril (n = 27) (n = 43) (n = 70) (% change) (% change) (% change)

Figure 5. Effect of ACE inhibitors on functional status as per NYHA class for HF in patients with LV systolic dysfunction and undergoing CABG. *Significantly different from other groups (p < 0.05). †Significantly

different from baseline (p < 0.05).

the percent improvement in LVEF from baseline levels was not statistically significant among the three groups, although it was slightly greater in perindopril and ramipril groups after 3 months as compared to captopril group and in captopril and perindopril groups at 6 months as compared to ramipril group.

The improvement in overall cardiac function could be because of better coronary blood flow due to inhibition of sympathetic coronary vasoconstriction by ACE inhibitors and due to inhibition of endothelial as well as adventitial ACE providing better hemodynamic control

by ACE inhibitors.36-38 This property of ACE inhibitors helps enhance coronary circulation and myocardial perfusion through newly placed grafts too.

In our earlier findings, we reported captopril and perindopril more efficient for improving LV contractility as compared to ramipril, lisinopril, and losartan.21

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CARDIOLOGY Captopril and perindopril were found to produce a significant increase in percent LVEF as compared to other ACE inhibitors and losartan. There was a significant correlation between decreases in blood glucose as well as insulin levels with improvements in LVEF.21 In the present work, the sustained and greater improvements observed in perindopril group could be secondary to improved glucose utilization by cardiac myocytes.

Moreover, greater improvement in arterial compliance and thus reduction in afterload by perindopril might be responsible for the improvement in LV contractility.

Afterload inversely affects LV contractility and has direct co-relationship with peripheral vascular resistance that is a measure of arterial compliance. Various ACE inhibitors, namely, captopril, lisinopril, and perindopril have been shown to increase arterial compliance.39-41 However, perindopril is the ACE inhibitor that has been reported to reduce media to lumen ratio of small arteries with significantly correlated LV mass reduction.42,43 Increasing the compliance (elasticity) of even larger arteries, in addition to reduction in peripheral resistance, is also an important documented property of perindopril.44 Perindopril has also been reported to improve patientâ&#x20AC;&#x2122;s hemodynamic status by improving the elasticity of resistance vessels in heart disease patients too.45,46 Furthermore, the improved compliance of conduits (by significant improvement in endothelial nitric oxide synthase expression and activity) and repair of coronary arterioles by perindopril could also be the contributing factor for greater improvement in LVEF.46-48 Besides indirect effects, direct effects of ACE inhibitors are of significance in patients with LV systolic dysfunction. Angiotensin-converting enzyme inhibitors prevent ventricular dilation and thereby reduce workload of heart with further improvement in its function. In our findings, the reduction in LV systolic and diastolic diameters was observed in all the three groups without any significant difference at 3 and 6 months of ACE inhibitor administration.

Evidences have shown that ACE inhibitors attenuate LV remodeling.16,17,25,49 The greater beneficial effects of perindopril on both diastolic and systolic diameters as compared to captopril and ramipril group is consistent with earlier report of Masuelli et al,50 which reported that perindopril reversed LV remodeling and improved functional status significantly in HF patients who had been switched over from enalapril treatment.50 The significant reduction in LVEDs by perindopril might be due to its direct effect on Tei index.51 Perindopril has a distinguished characteristic of suppressing cardiac aldosterone production, which is activated in failing ventricles, by suppressing cardiac ACE activity.52

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We found perindopril and ramipril treatments to produce negative effects on MR-grade after 3 and 6 months while captopril treatment showed favorable effects on this parameter after both 3 and 6 months of ACE inhibitor administration. Captopril is efficacious in reducing functional MR in dilated left ventricles; however, the doses used are high.53 MR results from a complex interaction of very small geometric and temporal changes and can occur as a result of multiple mechanisms that cannot be simply overcome by inhibiting ACE. All the ACE inhibitors used in our research (captopril, perindopril, and ramipril) were found to be effective in improving functional status. There was reduction in NYHA class in all the three groups from baseline levels. However, percent improvement in NYHA class at 6 months of ACE inhibitor treatment was significant in ramipril group only. This might be because of an increase in skeletal muscle perfusion during exercise and ability of ACE inhibitors to enhance endurance performance and muscle energy metabolism.54-57 Furthermore, various ACE inhibitors have been proved to significantly improve NYHA class for HF in patients with moderate-to-severe LV systolic dysfunction.58-61 Conclusion Our findings show that all three ACE inhibitors (i.e., captopril, perindopril, and ramipril) produce statistically comparable effects on heart in patients with LV systolic dysfunction undergoing CABG. While perindopril clinically produces a marginal superiority in cardiac function, ramipril produces the greatest improvement in functional capacity.

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33. Pilote L, Abrahamowicz M, Eisenberg M, Humphries K, Behlouli H, Tu JV. Effect of different angiotensinconverting-enzyme inhibitors on mortality among elderly patients with congestive heart failure. CMAJ 2008;178(10):1303-11.

34. Hansen ML, Gislason GH, Køber L, Schramm TK, Folke F, Buch P, Abildstrom SZ, Madsen M, Rasmussen S, TorpPedersen C. Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarction. Br J Clin Pharmacol 2008;65(2):217-23.

35. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davis JL, et al. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography), 2003.

36. Magrini F, Shimizu M, Roberts N, Fouad FM, Tarazi RC, Zanchetti A. Converting enzyme inhibition and coronary blood flow. Circulation 1987;75(1):I168-I174.

37. Perondi R, Saino A, Tio RA, Pomidossi G, Gregorini L, Alessio P, et al. ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 1992;85:2004-13.

38. Zhuo JL, Froomes P, Casley D, Liu JJ, Murone C, Chai SY, et al.

Perindopril chronically inhibits angiotensin converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease. Circulation 1997;96:174-82.

39. Asmar RG, Pannier B, Santoni JP, Laurent S, London GM, Levy BI, et al. Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension. Circulation 1988;78(4):941-50.

40. Chau NP, Simon A, Vilar J, Cabrera-Fischer E, PithoisMerli I, Levenson J. Active and passive effects of antihypertensive drugs on large artery diameter and elasticity in human essential hypertension. J Cardiovasc Pharmacol 1992;19(1):78-85.

41. Shimamoto H, Shimamoto Y. Lisinopril improves aortic compliance and renal flow: comparison with nifedipine.

Hypertension 1995;25(3):327-34.

42. Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ. Effect of antihypertensive treatment

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on small arteries of patients with previously untreated essential hypertension. Hypertension 1995;25(4 Pt 1):474-81.

43. Sihm I, Schroeder AP, Aalkjaer C, Holm M, Morn B, Mulvany M, et al. Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.

Blood Press 1995;4(4):241-8.

44. Hussar DA. New drugs of 1999. J Am Pharm Assoc 2000;40(2):181-221.

45. Kool MJ, Lustermans FA, Breed JG, Struyker-Boudier HA, Hoeks AP, Reneman RS, et al. The influence of perindopril and the diuretic combination amiloride + hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients. J Hypertens 1995;13(8):839-48.

46. Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE. Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 2000;36:220-5.

47. Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003;41:1281-6.

48. Comini L, Bachetti T, Cargnoni A, Bastianon D, Gitti GL, Ceconi C, et al. Therapeutic modulation of the nitric oxide: all ACE inhibitors are not equivalent. Pharmacol Res 2007;56(1):42-8.

49. Onodera H, Matsunaga T, Tamura Y, Maeda N, Takumi H, Sasaki S, et al. Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction. Am Heart J 2005;150(4):689.

50. Masuelli M, Brusca G, Pardo A, Pineiro D, Checkerdhemian S, Forcads P. ACE inhibitors in heart failure-switching from enalapril to coversyl. Curr Med Res Opin 2002;18:296-302.

51. Nearchou NS, Tsakiris AK, Lolaka MD, Zarcos I, Skoufas DP, Skoufas PD. Influence of perindopril on left ventricular global performance during the phase of inferior acute myocardial infarction: assessment by Tei index. Echocardiography 2003;20(4):319-27.

52. Mizuno Y, Yasue H, Yoshimura M, Fuji H, Yamamoto N, Nakayama M, et al. Effect of perindopril on aldosterone production in the failing human heart. Am J Cardiol 2002;89(10):1197-200.

53. Seneviratne B, Moore GA, West PD. Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial. Br Heart J 1994;72(1):63-8.

54. Mancini DM, Davis L, Wexler JP, Chadwick B, LeJemtel TH. Dependence of enhanced maximal exercise performance on increased peak skeletal muscle perfusion during longterm captopril therapy in heart failure. J Am Coll Cardiol 1987;10:845-50.

55. Willenheimer R, Rydberg E, Öberg L, Juul-Möller S, Erhardt L. ACE inhibition with ramipril improves left ventricular function at rest and post exercise

CARDIOLOGY in patients with stable ischaemic heart disease and preserved left ventricular systolic function. Eur Heart J 1999;20(22):1647-56.

56. Banerjee A, Talreja A, LeJemtel TH. Evolving rationale for angiotensin converting enzyme inhibitor therapy in chronic heart failure. Mt Sinai J Med 2003;70:225-31.

57. Bahi L, Koulmann N, Sanchez H, Momken I, Veksler V, Bigard AX, et al. Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?

J Appl Physiol 2004;96:59-64.

58. Lamas GA, Vaughan DE, Parisi AF, Pfeffer MA. Effects of left ventricular shape and captopril therapy on exercise

capacity after anterior wall acute myocardial infarction.

Am J Cardiol 1989;63(17):1167-73.

59. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991;325:293-302.

60. Hutcheon SD, Gillespie ND, Crombie IK, Struthers AD, McMurdo ME. Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomized double blind placebo controlled trial. Heart 2002;88(4):373-7.

61. Barrios AV, Pena PZ, Campuzano RR, Lombera RF, Peralta Y. Utility of perindopril in mild-moderate heart failure in daily clinical practice. Rev Clin Esp 2003;203(1):3-9.

■■■■

Cherish and Share Love in Life Many years ago all feeling and emotions gathered to spend their vacation on a coastal island. Each of them was having a good time, but one day a warning of a storm was announced and everyone had to leave the island.

This caused a panic, all rushed to their boats and only Love did not wish to be in a hurry. There was so much to do, so Love was the last, who realized that it was time to leave. However, no free boats were left and Love looked around with hope.

As Prosperity was passing by in its classy boat, Love asked, "Please, take me in your boat." But Prosperity replied, "My boat is full of gold and other precious possessions, there is no place for you."

Then Vanity came by in a lovely boat. Love asked, “Vanity, could you take me in your boat? Please, help me.”

Vanity said, "No, your feet are muddy, and I don’t want my boat get dirty."

Some time later Sorrow was passing by and Love called for help. But Sorrow answered, "I am so sad, I want to be by myself."

Then Happiness came by, Love asked for help, but Happiness was too happy, it was hardly concerned about anyone.

Suddenly somebody called out, "Love, I will take you with me." Love did not recognize its savior, just gratefully jumped on to the boat.

When everyone had reached safe place, Love got off the boat and met Knowledge. Love asked, "Knowledge, do you know who helped me when everyone else turned away?"

Knowledge smiled, "That was Time, because only Time knows Love’s true value and what Love is capable of.

Only Love can bring peace and happiness."

The message of this story is that when we are prosperous, we underrate Love. When we feel important, we do not appreciate love. And even in happiness and sorrow we overlook love. Only with time we realize the true value of love. Why wait and not cherish and share Love every day of your life?

Source: eMedinewS Dec 28, 2013

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

741

CARDIOLOGY

Acute Renal Failure and Silent Myocardial Infarction Following Multiple Honey Bee Stings Kavina Marian Fernandes*, Gadwalkar Srikant R**, Shyamala Gâ&#x20AC;

Abstract Massive envenomation by honey bee sting is capable of causing multiorgan dysfunction as a result of direct toxic effect of venom and secondary to systemic anaphylactic reactions. Myocardial infarction (MI) due to honey bee sting is rare, so is acute renal failure (ARF). The probable mechanism is severe coronary arterial spasm with secondary in situ thrombosis as a result of systemic anaphylaxis. This is a case of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation. We describe a case of ARF and MI in a 58-year-old man after multiple honey bee stings; clinically silent and detected on electrocardiography and by cardiac biomarkers.

Keywords: Acute myocardial infarction, acute renal failure, massive honey bee envenomation, Kounis syndrome

H

ymenoptera sting envenomation may result in a number of clinical presentations: 1) nonallergic, local reactions (pain, minor edema, redness at the sting site); 2) allergic, large local reactions (extensive swelling >10 cm persisting for >24 hours); 3) anaphylaxis (generalized urticaria, angioedema, bronchospasm, hypotension, cardiovascular collapse, and loss of consciousness); 4) systemic toxic reactions (edema, vomiting, diarrhea, headache, seizures and altered sensorium) and 5) unusual reactions (cardiac ischemia, encephalomyelitis, and cerebral infarctions).1 We report a case of massive bee sting envenomation with unusual manifestations of acute myocardial infarction (AMI) and acute renal failure (ARF).

hypertensive on regular treatment. No past history of diabetes mellitus, ischemic heart disease or dyspnea on exertion or angina.

He was brought to our emergency department eight hours after the bee stings. On admission, his pulse rate was 98 beats/minute, blood pressure was 90/60 mmHg, respiratory rate was 18/minute and oxygen saturation was 98% at room air. There were multiple stings on face, head, arms, chest, back and legs. There was marked edema of face and lips with diffuse urticaria over the entire body. He had rhonchi in all lung fields.

Rest of the systemic examination was normal.

Hematological examination revealed total leukocyte counts (30,760 cells/mm3), and reduced platelet counts

CASE PRESENTATION A 58-year-old forest official (Fig. 1), presented to us with a history of multiple bee stings (>200). He had been immediately admitted to a local hospital with swelling of lips and face. He was given preliminary care (treatment details are not known) and was referred to our hospital with dyspnea and decreased urine output.

He had dark colored urine. There was no history of chest pain, palpitations, syncope, seizure or altered sensorium. He was a chronic smoker. He was a known

*Postgraduate Student **Professor and Head â&#x20AC; Professor Dept. of General Medicine Vijayanagar Institute of Medical Sciences, Bellary, Karnataka

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

Figure 1. Patient with multiple stings and swelling of lips and face on third day of hospital admission.

CARDIOLOGY DISCUSSION Massive honey bee envenomation is defined as more than 50 stings at a time. Individuals who are highly allergic to the venom may develop severe systemic anaphylaxis (type I hypersensitivity) from a single sting. Massive bee attacks can result in toxic reactions, regardless of pre-existing allergic conditions, by virtue of a high venom load potentially causing multiorgan dysfunction.1

Figure 2. Electrocardiograph of the patient on the day of admission showing ST segment elevation in lead II, III and aVF, reciprocal ST depression was seen in lead I, aVL.

(58,000 cells/mm3). Renal parameters were elevated (urea, 62 mg/dl; creatinine, 3.3 mg/dl). Serum electrolytes were normal (sodium, 136 mmol/l; potassium, 4.2 mmol/l; chloride 106 mmol/l). Electrocardiograph showed ST segment elevation in lead II, III and aVF, reciprocal ST depression was seen in lead I, aVL (Fig. 2). Urine microscopy showed 10-12 pus cells and albuminuria 2+, troponin I was elevated (28.046 ng/ml).

ECG showed no further progression of ST elevation or poor progression of R waves. 2D-Echo showed normal cardiac chambers, normal cardiac valves, regional wall motion abnormality in inferior wall, ejaculation fraction (EF) was 55%.

He was given injection hydrocortisone 100 mg intravenously q6h, injection chlorpheniramine maleate 25 mg q12h and injection ranitidine 50 mg q8h. He was hydrated with IV fluids. Injection epinephrine 0.3 mg IM was repeated thrice. Injection noradrenaline was given as an infusion at the rate of 1 Îźg/min. He was started on anticoagulants and oral antiplatelets.

Next day renal parameters increased (urea, 101 mg/dl; creatinine, 5.1 mg/dl). Ultrasonography of abdomen showed Grade I renal parenchymal disease with normal sized kidneys. Urine output did not improve in spite of above measures. He was dialyzed on alternate days.

His renal function gradually improved. ECG changes were reversed to almost normal limits.

Angioedema and urticaria also resolved completely.

Injection hydrocortisone was gradually tapered and stopped. He was switched to oral pheniramine maleate and ranitidine and discharged in 10 days. Patient was referred to higher center for further evaluation, where angiogram was done and reported to be normal.

The clinical and pathophysiological background of AMI after a bee sting is generally related to different mechanisms. Hymenoptera venom can cause acute myocardial injury by several mechanisms: a) AMI occurring in subjects without significant coronary artery disease because of coronary thrombosis and vasospasm enhanced by intoxication.2 Release of allergenic proteins, vasoactive (epinephrine, dopamine), inflammatory (leukotrienes), thrombogenic peptides and amine constituents (histamine, serotonin, bradykinin, leukotrienes, thromboxane), which act on the coronary vasculature and induce coronary artery vasospasm and facilitate platelet aggregation as well as thrombosis. Paradoxical vasoconstriction could be an underlying mechanism. Severe coronary arterial spasm or secondary in situ thrombosis may also play a role in such a case3; b) direct cardiotoxic effect of the venom; and c) anaphylactic reaction. Anaphylactic reactions which result in acute coronary syndromes is also known as Kounis syndrome.4 Hymenoptera sting can lead to an AMI by different pathogenetic mechanisms depending on the presence of pre-existent coronary atherosclerosis, the development of shock or the therapeutic use of epinephrine.

Vasoactive amines, including histamine, dopamine and noradrenaline can provoke ischemia and even MI through profound hypotension and arrhythmia, or by increasing oxygen demands through direct inotropic and chronotropic effects in the presence of pre-existing ischemic heart disease.5 In patients with AMI after multiple bee stings as reported in literature, the coronary arteries were normal or insignificantly stenosed. Electrocardiographic changes consistent with acute myocardial ischemia or infarction, including ST depression or elevation and even the appearance of pathologic Q-waves, are seen in these patients. Rhythm abnormalities such as supraventricular arrhythmias, VPCs, junctional rhythm and right bundle branch block may occur.4 Inflammatory mediators, adhesion molecules of neutrophils and monocytes, have been shown to be

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

743

CARDIOLOGY increased in the plasma of patients presenting with acute coronary syndromes. Anaphylaxis is a systemic, immediate hypersensitivity reaction caused by rapid IgE-mediated release of mediators from mast cells and basophils. In 1991, Kounis and Zavras6 described the 'syndrome of allergic angina' as the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classical angina pectoris caused by inflammatory mediators released during the allergic insult.

Allergic angina can progress to AMI, which was named “allergic myocardial infarction.”7 In 1998, Braunwald,8 in an editorial, noted that vasospastic angina can be induced by “allergic reactions with mediators such as histamine or leukotrienes acting on coronary vascular smooth muscle.”

There are two variants of this syndrome that have been described recently.9 Type Ι variant includes patients with normal coronary arteries without predisposing factors for coronary artery disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm leading to unstable angina or coronary vasospasm progressing to AMI. This variant might represent a manifestation of endothelial dysfunction. Type II variant includes patients with culprit but quiescent pre-existing atheromatous disease in whom acute allergic episode can induce plaque erosion or rupture manifesting as an AMI. If the clinical judgment favors the use of aspirin in these patients, it seems reasonable to give it after the initial treatment for Kounis syndrome has been started. Use of IV or sublingual nitroglycerin seems reasonable and safe if the blood pressure is satisfactory. b-blockers may offset some of the beneficial effects of epinephrine. Heparin bolus should be avoided.

Heparin should be used at low dose at a slow infusion rate. Calcium channel blockers may be considered the initial anti-ischemic drug of choice in patients with Kounis syndrome.10 Bee venom exposure may be associated with albuminuria.11 ARF following bee stings is a rare complication. Following bee stings, biphasic renal failure has been documented with early renal failure due to hemolysis and a second episode of azotemia about 10 days later occurring in conjunction with depressed serum complement C3 level and nephritic changes on renal biopsy. The major causes of renal failure are acute tubular necrosis (ATN) due to hypotension or pigment nephropathy resulting from rhabdomyolysis and intravascular hemolysis, and acute interstitial nephritis.12 Renal failure has resulted

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

from stings ranging from 22 to 1,000 in number.

The exact mechanism of rhabdomyolysis is not known but a direct toxic effect of venom on muscle is believed to be the main cause.13 However, other mechanisms postulated for renal damage due to bee stings are: 1) direct nephrotoxicity due to toxin; 2) hypotension leading to ischemic tubular necrosis; and 3) nephropathy due to hemoglobinuria and myoglobinuria.14 Reported systemic complications following multiple bee stings include ARF, myocarditis, MI, centrilobular necrosis of liver, acute encephalopathy, Guillain-Barre syndrome, vasculitis, disseminated intravascular coagulation and thrombocytopenia.15 CONCLUSION Of particular interest in the present case report is the silent presentation of MI. Clinical presentation may be quite different in AMI patients after bee stings. It may be completely silent, or ECG changes such as ST wave elevation may occur several hours after admission.

Therefore, a higher clinical suspicion is absolutely necessary to make a correct diagnosis. It follows that in any case of hymenoptera envenomation a standard ECG is advisable. Also, serial ECG recordings are recommended in every patient who complains of chest pain, regardless of the severity of the patient's reaction to a bee sting. Maintaining adequate urine output should be instituted with aggressive hydration to reduce the likelihood of rhabdomyolysis-induced renal insufficiency. In conclusion, massive bee envenomation can cause life-threatening complications like acute myocardial injury, rhabdomyolysis, hemolysis with ARF, and systemic anaphylaxis.

REFERENCES 1. Betten DP, Richardson WH, Tong TC, Clark RF. Massive honey bee envenomation-induced rhabdomyolysis in an adolescent. Pediatrics 2006;117(1):231-5.

2. Ceyhan C, Ercan E, Tekten T, Kirilmaz B, Onder R. Myocardial infarction following a bee sting. Int J Cardiol 2001;80(2-3):251-3.

3. Massing JL, Bentz MH, Schlesser P, Dumitru C, Louis JP. Myocardial infarction following a bee sting. Apropos of a case and review of the literature. Ann Cardiol Angeiol (Paris) 1997;46(5-6):311-5.

4. Yang HP, Chen FC, Chen CC, Shen TY, Wu SP, Tseng YZ. Manifestations mimicking acute myocardial infarction after honeybee sting. Acta Cardiol Sin 2009;25:31-5.

5. Riches KJ, Gillis D, James RA. An autopsy approach to bee sting-related deaths. Pathology 2002;34(3):257-62.

6. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract 1999;45(2):121-8.

CARDIOLOGY 7. Kounis NG, Zavras GM. Allergic angina and allergic myocardial infarction. Circulation 1996;94(7):1789.

12. Patil PL, Salkar HR. Wasp sting induced acute renal failure. Indian J Nephrol 2004;14:30-1.

8. Braunwald E. Unstable angina: an etiologic approach to management. Circulation 1998;98(21):2219-22.

13. Kim YO, Yoon SA, Kim KJ, Lee BO, Kim BS, Chang YS, et al. Severe rhabdomyolysis and acute renal failure due to multiple wasp stings. Nephrol Dial Transplant 2003;18(6):1235.

9. Nikolaidis LA, Kounis NG, Gradman AH. Allergic angina and allergic myocardial infarction: a new twist on an old syndrome. Can J Cardiol 2002;18(5):508-11.

10. Cevik C, Nugent K, Shome GP, Kounis NG. Treatment of Kounis syndrome. Int J Cardiol 2010;143(3):223-6.

14. Dos Reis MA, Costa RS, Coimbra TM, Dantas M, Gomes UA. Renal changes induced by envenomation with Africanized bee venom in female Wistar rats. Kidney Blood Press Res 1997;20(4):271-7.

15.

11. Elming H, Sølling K. Urine protein excretion after Hymenoptera sting. Scand J Urol Nephrol 1994;28(1):13-5.

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Daher Ede F, da Silva Júnior GB, Bezerra GP, Pontes LB, Martins AM, Guimarães JA. Acute renal failure after massive honeybee stings. Rev Inst Med Trop Sao Paulo 2003;45(1):45-50.

Rights of a FMT Specialist Q. I am a senior FMT specialist. About 4 months ago, an ASI conveyed the verbal request from his boss to get an autopsy performed by a board of doctors and to certify the cause of death as heart attack. My interpretation is as follows: a. The police have doubted the honesty and integrity of the autopsy surgeon without knowing his identity. b. The action of the police in making the request amounts to defamation and I can file a case alleging defamation. c. Many people do not know in which cases other than section 304B, IPC, should autopsy be done by a board of doctors?

What are your comments?

Answer ÂÂ

A request for examination by a board of doctors does not mean casting a doubt on somebody’s honesty or integrity or defaming somebody.

ÂÂ

There cannot be defamation against a person whose identity is not known.

ÂÂ

Section 304B, IPC, has nothing in it regarding a medical board.

ÂÂ

There are no clear guidelines regarding when a medical board should be formed. For example, the recent Kerala Medico-Legal Code is silent about it. The fact is that the formation of a board for performing autopsy has to be under written instructions from a court or other competent authority.

ÂÂ

An FMT specialist should not take any verbal instructions from anybody.

ÂÂ

No professional expert, including an FMT specialist, should ever give up his professional independence as an expert. You would be within your rights to inform the Commissioner Police/SSP about the illegal request made by the ASI, including his “instructions” to report the cause of death as heart attack.

Source: emedinews

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

745

CARDIOLOGY

Perioperative Myocardial Infarction Sudivya Sharma, Prashast Jain

Abstract Myocardial infarction (MI) is defined by the World Health Organization Criteria, which includes typical ischemic chest pain, ECG criteria and raised cardiac enzymes. The perioperative period induces large, unpredictable and nonphysiological alterations in coronary plaque morphology, function and progression, and may trigger a mismatch of myocardial oxygen supply and demand.

Perioperative MI (PMI) is one of the most important predictors of short- and long-term morbidity and mortality associated with noncardiac surgery. Inability to fulfil the criteria, different symptomatology and numerous differential diagnoses makes PMI our subject of detailed discussion.1

Keywords: Perioperative myocardial infarction, plaque rupture, ischemia, risk stratification

T

he incidence of perioperative cardiac injury is a cumulative result of preoperative medical condition, the specific surgical procedure, expertise of the surgeon, the diagnostic criteria used to define myocardial infarction (MI) and the overall medical care at a particular institution. Patients with or at risk of cardiac disease have a 3.9% risk of suffering a major perioperative cardiac event. A perioperative MI (PMI) has an associated in-hospital mortality of 15-25% and an increased risk of subsequent cardiovascular death or MI.2,3 Most PMIs occur in the first 24-48 hours after surgery.

They are mostly of silent type; ECG changes include ST depression, tachycardia and absence of Q waves and ST elevation. There is complete reversal of ECG changes to the baseline. The pain is masked by the analgesia and residual anesthesia provided intraoperatively.

The prolonged stress-induced mismatch between oxygen supply and demand is the most likely cause of myocardial ischemia.

A study of aortic surgical patients identiďŹ ed three patterns of troponin elevation. It was proposed by the authors that coronary plaque rupture was consistent with early PMI due to the rapidity of troponin change, while a sustained myocardial oxygen supply-demand imbalance in the postoperative period was consistent with delayed MI.4

PGIMS, Rohtak, Haryana Address for correspondence Dr Sudivya Sharma Flat No: 77, B-Wing, Mahavir Krupa building TJ Road, Sewri (W), Mumbai-400 015

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Pathophysiology One hypothesis supports sudden development of a thrombotic process associated with vulnerable plaque rupture. This hypothesis is based on postoperative autopsy studies and angiographic evidence of thrombus present in noncritically stenosed vessels.

Endothelial injury at the site of a plaque rupture triggers the cascade of platelet aggregation and release of mediators including thromboxane A2, serotonin, adenosine diphosphate, platelet-activating factor, thrombin, and oxygen-derived free radicals. Aggregation of platelets and activation of other inflammatory and noninflammatory mediators potentiates thrombus formation and leads to dynamic vasoconstriction distal to the thrombus. The combined effects of dynamic and physical blood vessel narrowing cause ischemia and/ or infarction. In the postoperative period, changes in blood viscosity, catecholamine concentrations, cortisol levels, endogenous tissue plasminogen activator concentrations, and plasminogen activator inhibitor levels create a prothrombotic state. Changes in heart rate and blood pressure as a result of the endocrine stress response can increase the propensity for plaque fissuring and endothelial damage.

These MIs are preceded by tachycardia and ST depression, are often silent and present as non-STsegment elevation MI (NSTEMI). Patients with more severe coronary artery disease (CAD) are at greater risk.

These observations support the other likely hypothesis that perioperative myocardial injury develops as a consequence of increased myocardial oxygen demand (increased blood pressure and heart rate) in the context of underlying compromised myocardial oxygen supply.

CARDIOLOGY The oxygen demand is increased perioperatively due to increased heart rate, heart wall tension, preload, afterload, and myocardial contractility. On the other hand, the oxygen supply is decreased due to decreased coronary blood flow, tachycardia, hypotension, hypocapnia, hypoxemia, anemia, etc.

In combination, these factors can precipitate thrombus formation in an atherosclerotic coronary artery and lead to the development of STEMI (Q-wave).

Thus, two different pathophysiologic mechanisms

Table 1. Clinical Predictors of Increased Perioperative Cardiovascular Risk Major Unstable coronary syndromes

Acute or recent MI with evidence of important ischemic risk by clinical symptoms or noninvasive study

nstable or severe angina U Decompensated heart failure

Significant dysrhythmias

High-grade atrioventricular block

Symptomatic ventricular dysrhythmias in the presence of underlying heart disease

can be responsible for PMI. One could be related to acute coronary thrombosis, and the other could be the consequence of increased myocardial oxygen demand in the setting of compromised myocardial oxygen supply. These processes are not mutually exclusive.

However, one process or the other can predominate in a particular patient.

Risk Stratification Tables 1-4 are guides to risk stratification for a patient, predicting likelihood of myocardial ischemia or infarction perioperatively. The severity of surgery, the functional capacity and present cardiac clinical signs and symptoms collectively determine the prognosis and outcome of surgery. These are also a guide for further delay or optimization of the patient. Figure 1 shows a step-wise approach to patients at risk.

Table 2. Revised Cardiac Risk Index in Patients Undergoing Elective Major Noncardiac Surgery High-risk surgery Abdominal aortic aneurysm Peripheral vascular operation

Supraventricular dysrhythmias with uncontrolled ventricular rate Severe valvular heart disease

Thoracotomy

Intermediate

History of myocardial infarction

Mild angina pectoris

History of a positive exercise test

Previous MI by history or Q waves on ECG Compensated or previous heart failure Diabetes mellitus (particularly insulin dependent) Renal insufficiency Minor Advanced age (older than 70 years) Abnormal ECG (left ventricular hypertrophy, left bundle branch block, ST-T abnormalities) Rhythm other than sinus Low functional capacity History of stroke Uncontrolled systemic hypertension (Adapted from Fleisher LA, Beckman JA, Brown KA, et al: ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: Focused update on perioperative beta-blocker therapy: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2006;113: 2662-2674. with permission.)

Major abdominal operation Ischemic heart disease

Current complaints of angina pectoris Use of nitrate therapy Q waves on electrocardiogram Congestive heart failure History of congestive heart failure History of pulmonary edema History of paroxysmal nocturnal dyspnea Physical examination showing rales or S3 gallop Chest radiograph showing pulmonary vascular redistribution Cerebrovascular disease History of stroke History of transient ischemic attack Insulin-dependent diabetes mellitus Preoperative serum creatinine concentration > 2 mg/dl Adapted from Lee TH, Marcantonio ER, Mangione CM, et al: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043–1049 with permission.

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747

CARDIOLOGY Table 3. Metabolic Equivalents of Functional Capacity MET

Functional levels of exercise

1

Eating, working at a computer, dressing

2

Walking down stairs or in your house, cooking

3

Walking 1-2 blocks

4

Raking leaves, gardening

5

Climbing 1 flight of stairs, dancing, bicycling

6

Playing golf, carrying clubs

7

Playing singles tennis

8

Rapidly climbing stairs, jogging slowly

9

Jumping rope slowly, moderate cycling

10

Swimming quickly, running or jogging briskly

11

Skiing cross country, playing full-court basketball

12

Running rapidly for moderate to long distances

Step 1

Table 4. Cardiac Risk Stratification for Noncardiac Surgical Procedures Risk stratification

Vascular (reported yy Aortic and other major vascular surgery cardiac risk often yy Peripheral vascular surgery > 5%) Intermediate (reported cardiac risk generally 1-5%)

yy Intraperitoneal and intrathoracic surgery yy Carotid endarterectomy yy Head and neck surgery yy Orthopedic surgery yy Prostate surgery

Low (reported cardiac risk generally < 1%)

yy Endoscopic procedures yy Superficial procedure yy Cataract surgery yy Breast surgery yy Ambulatory surgery

Operating room

Perioperative surveillance and postoperative risk stratification and risk factor management

Evaluate and treat per ACC/AHA guidelines

Consider operating room

Yes (Class I, LOE C)

Need for emergency noncardiac surgery?

Procedure examples

No Yes (Class I, LOE B)

Step 2

Active cardiac conditions

Step 3

Low risk surgery

Step 4

Functional capacity â&#x2030;Ľ4 METs without symptoms.

Step 5

Proceed with planned surgery

Yes (Class I, LOE B)

Yes (Class IIa, LOE B)

No or unknown

3 or more clinical risk factors Vascular surgery

1-2 1-2 clinical clinical risk risk factors factor

Vascular surgery

Intermediate risk surgery

Proceed with planned surgery with HR control (Class IIA LOE B) or consider noninvasive testing (Class IIb LOE B) if it will change management

Figure 1. Risk stratification and management.

748

No clinical risk factor

Intermediate risk surgery

Class IIa LOE B Consider testing if it will change management

Proceed with planned surgery

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

Class IIa LOE B

Proceed with planned surgery

CARDIOLOGY The goal is to identify patients with heart disease who are at high-risk for perioperative cardiac morbidity or mortality or those with modifiable conditions or risk. The guidelines for cardiac evaluation before noncardiac surgery published by the ACC/AHA have become the national standard of care. These guidelines were recently revised with a marked reduction in recommendations for preoperative noninvasive stress testing and revascularization. The substantial pullback of ACC/AHA recommendations advocating noninvasive stress testing and coronary revascularization before noncardiac surgery is due to the general lack of definitive benefit and risk reduction with this approach.5 Preoperative period is an opportunity to identify patients with CAD who will benefit from long-term risk modification with statins, aspirin, exercise and diet adjustment. Patients with symptoms consistent with ischemia (but without a diagnosis of CAD) or significant risk factors without medical management such as statins and aspirin may benefit from evaluation by a cardiologist regardless of whether they are having surgery. Preoperative evaluation should not simply focus on perioperative risk.

Management The management of PMI is also different as thrombolytics cannot be given, and anticoagulant use is with caution. The risk of life-threatening bleeding cancels thrombolytics as an option, hence a more conservative approach is recommended. So, the mainstay of treatment includes good pain control, β-blockers, statins, antiplatelets, nitroglycerine, and unfractionated heparin.

Conclusion Many questions relating to perioperative pharmacological therapy to prevent PMI remain unanswered.

Careful perioperative monitoring for ischemia, a low threshold for treating and preventing tachycardia while avoiding hypotension, decreased cardiac output and/or cardiac decompensation help prevent PMI. Coronary intervention is rarely indicated as the firstline of treatment, and antithrombotic therapy may exacerbate bleeding. Future studies are needed to determine, which patients with PMI require intensified postoperative surveillance, medical therapy and/or coronary intervention to improve long-term survival.

References 1. Priebe HJ. Perioperative myocardial infarction aetiology and prevention. Br J Anaesth 2005;95(1):3-19.

2. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk.

CMA J 2005;173(6):627-34.

3. Devereaux PJ. Can attenuation of the perioperative stress response prevent intermediate or long-term cardiovascular outcomes among patients undergoing noncardiac surgery? Anesthesiology 2009;111(2):223-6.

4. Le Manach Y, Perel A, Coriat P, Godet G, Bertrand M, Riou B. Early and delayed myocardial infarction after abdominal aortic surgery. Anesthesiology 2005;102(5):885-91.

5. Fleisher LA, Beckman JA, Brown KA, et al: ACC/ AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol 2007; 50:159-241.

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Be Cautious in Giving Painkiller to Patients with High Cholesterol Long-term non-steroidal anti-inflammatory painkiller drugs (NSAIDs) such as naproxen should not be prescribed to patients with high cholesterol.

In a swine model study published in Surgery Dr Frank Sellke, chief of cardiothoracic surgery and research at Rhode Island Hospital found that a high-cholesterol diet reduced blood flow to the heart muscle in animal models with chronic heart disease when given daily naproxen. They also found reduced levels of prostacyclin, a compound that dilates blood vessels and prevents blood clots.

These findings suggest that there may be a stronger risk of negative effects on the heart in patients who have high cholesterol levels and are taking NSAIDs as a form of pain or inflammation relief.

Source: emedinews

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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Drug

Spinosad: A Newer Anti-Lice Drug AK Sharma*, JK Kairi†

Abstract Head lice infestation is a common and highly contagious condition caused by pediculus humanus capitis. Therapy for head lice infestation has been traditionally combing out the live lice and the unhatched eggs (nits) by a fine toothed comb along with topical chemical treatments. Emergence of resistance to these therapies compromises their effectiveness. As a result, the search for newer agents has been a clinical necessity. Recently, spinosad, a newer anti-lice drug, has been approved by US FDA as 0.9% topical suspension. Spinosad provides a useful alternative for children above 4 years of age suffering from head lice infestation.

Keywords: Pediculus humanus capitis, head lice, infestation, resistance, spinosad DRUG UPDATE: SPINOSAD Pediculus humanus capitis causes the common and highly contagious clinical condition known as head lice infestation. As per current estimates the global burden of the infestation is huge and in India incidence ranges from 16.59-59.7%.1 The infestation spreads by simple direct head to head contact. The pediatric age group contributes to most infestations. Children so infested suffer not only from inconvenience but also become targets for ridicule and ostracization at school and places of play. Hence, it becomes imperative to treat such children at the earliest and achieve cure in shortest possible time with minimum adverse effects.

Therapy for head lice infestation has been traditionally combing out the live lice and the unhatched eggs (nits) by a fine toothed comb along with topical chemical treatments linked to the life cycle of the parasite.

Till now the compounds that have been recommended for anti-lice treatment are pyrethrin (1%), lindane (1%), and malathion (0.5%).2 The susceptibility of the life stages of the louse to various chemical treatments is illustrated in Fig. 1. and their characteristics have been compared in Table 1.

*Professor and Head

Dept. of Pharmacology, AFMC, Pune

†Pharmacologist

Military Hospital, Assam Address for correspondence Dr AK Sharma Professor and Head Dept. of Pharmacology AFMC, Pune-411 040 E-mail: ashse16@rediffmail.com

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

Ova

Spinosad Malathion

Nymph

Lindane Pyrethrin

Adult Louse

Figure 1. Stages of head lice life cycle affected by various anti-lice drugs.

It is clearly evident from the aforementioned account that none of the mainstream anti-pediculicides is close to ideal and emergence of resistance to these therapies further compromises their effectiveness. Even the nit combing approach has controversies associated with it. Some experts recommend it routinely while others are not so particular.5 As a result, the search for newer agents has been a clinical necessity. A large number of compounds have been tried out for this indication including (a) Topical use of ivermectin (0.5%) and benzyl alcohol (5%): Though approved by US FDA, their role in therapy is still emerging.6,7 (b) Orally ivermectin and co-trimoxazole: Not yet approved by US FDA by this route for this indication and are being tried as ‘off label’ treatments.8 In addition, the safety and efficacy of both these oral agents have not been conclusively established. Recently, spinosad, a newer

Drug Table 1. Comparison of Various Conventionally Used Anti-lice Drugs Compound Stage of louse life cycle affected

No. of Mechanism of applications action recommended

Preferred or not

Incidence of resistance

Remarks

Hyperstimulates GABA receptor to paralyse the louse and prevent it from feeding

No, due to requirement of large number of applications and safety concerns

Numerous reports document it

Recommended for single application of 4 minutes duration due to concerns of neurotoxicity even though, two to three applications are needed for efficacy.3

Lindane

Mostly adult

1

Pyrethroids (permethrin and pyrethrin)

Mostly adult

2-3

Acts on Na+ channels to cause delayed repolarization leading to paralysis in louse, and preventing it from feeding

Yes, primarily Widespread because of better safety profile

Malathion

Adult and eggs

1-2

Excessive stimulation of cholinergic neurons causes hyperexcitability and prevents louse from feeding

Yes, excipients in the formulation add to efficacy

anti-lice drug, has been approved by US FDA as 0.9% topical suspension.

Chemistry Spinosad is fermentation product of the soil bacterium, Saccharopolyspora spinosa, containing a mixture of spinosyn A and spinosyn D in a ratio of approximately 5:1. It was initially introduced as an agricultural insecticide and later was found efficacious for animal and human infestations.

Rare

Even though considered generally very safe, but severe asthma exacerbations have been reported rarely.4 For enhancing its efficacy, nit combing is highly recommended Considered most efficacious, however, due to safety concerns of accidental oral ingestion, it was withdrawn form the US markets and reintroduced in 1998.

Mechanism of action Spinosad acts by stimulating nicotinic receptors in the lice to produce excessive neuronal excitation that causes neuromuscular fatigue leading to paralysis and eventually death of the lice.9

Pharmacokinetics Spinosad is not significantly absorbed systemically when used topically in patients.10

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751

Drug Efficacy Compared to Existing Therapies A single application of spinosad suspension (0.9%) without nit combing has been found to be an effective, safe and more convenient therapy compared to permethrin (1%) with nit combing for head lice in the majority of patients.11 How to Use After thorough shaking, the suspension should be applied on the entire fully dry scalp and hair and left for 10 minutes. The application should be washed off with warm water. A second application is recommended if live lice are seen after seven days of initial application.

Special care must be taken to prevent the entry of the compound into the eyes.

Adverse Effects As it is not significantly absorbed systemically on topical use, no serious adverse effects have been reported. However, application site erythema, irritation and conjunctival irritation were reported in less than 3% subjects in two clinical trials.11 The safety of the product has not been established for children below four years of age. Benzyl alcohol, present in the formulation though known to be toxic to neonates in case of systemic exposure, is unlikely to be harmful to either adults or children because of the topical use and low concentration present in the formulation. There is no evidence of significant absorption of benzyl alcohol in adults or children when used by topical route.7 Safety in Pregnancy and Lactation In animal studies, spinosad has not caused any significant teratogenic effects but due to lack of data in humans, the drug should be used only when it is unavoidable i.e. failure of therapy with other agents.

In lactating women, breast feeding may be suspended for about 8 hours post-application as additional safety measure.

SUMMARY Head lice infestation, also known as Pediculosis capitis, is a commonly encountered problem in clinical practice, especially in children. Because of differential susceptibility of various life stages of lice to conventional therapeutic chemical agents, eradicating the infestation by a single topical application of any agent has been unreliable and unsatisfactory so far. Over a period of

time, the lice too have become resistant to many of the agents that have been traditionally used. Safety issues have been additional concern with the use of conventional anti-lice chemical therapies. Recently approved by the US FDA, Spinosad suspension (0.9%) offers a novel, effective and safer option to treat head lice infestation.

Conclusions Spinosad provides a useful alternative for children above 4 years of age suffering from head lice infestation and its safety profile and efficacy are superior to the other established treatments for this indication.

References 1. Khokhar A. A study of pediculosis capitis among primary school children in India. Indian J Med Sci 2002;56:449-52.

2. Nutanson I, Steen CJ, Schwartz RA, Janniger CK. Pediculus humanus capitis: an update. Acta Dermatoven APA 2008;17(4):147-59.

3. Nolan K, Kamrath J, Levitt J. Lindane toxicity: a comprehensive review of the medical literature. Pediatr Dermatol 2012;29(2):141-6.

4. Wax PM, Hoffman RS. Fatality associated with inhalation of a pyrethrin shampoo. J Toxicol Clin Toxicol 1994;32:457-60.

5. Meinking TL, Clineschmidt CM, Chen C, et al. An observer-blinded study of 1% permethrin crème rinse with and without adjunctive combing in patients with head lice. J Pediatrics 2002;141(5):665-70.

6. Pariser DM, Meinking TL, Bell M, Ryan WG. Topical 0.5% ivermectin lotion for treatment of head lice. N Engl J Med 2012;367(18):1687-93 7. Meinking TL, Villar ME, Vicaria M, et al. The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice pediculosis humanus capitis). Pediatr Dermatol 2010;27(1):19-24.

8. Chosidow O, Giraudeau B, Cottrell J, Izri A, Hofmann R, Mann SG, et al. Oral ivermectin versus malathion lotion for difficult-to-treat head lice. N Engl J Med 2010; 362(10):896-905.

9. Salgado VL. Studies on the mode of action of spinosad: insect symptoms and physiological correlates. Pesticide Biochem Physiol 1998;60(2):91-02.

10. McCormack PL. Spinosad: in pediculosis capitis. Am J Clin Dermatol 2011;12(5):349-53.

11. Stough D, Shellabarger S, Quiring J, Gabrielsen AA Jr. Efficacy and safety of spinosad and permethrin creme rinses for pediculosis capitis (head lice). Pediatrics 2009;124(3):e389-95.

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ENT

Knowledge, Awareness, and Practices Among Patients with Thyroid Swelling Attending Cytology Clinic in a Medical College, Meerut A Singh*, B Sachan†, NP Malik‡, VK Sharma||, N Verma§, CP Singh ¶

Abstract Background: Thyroid disorders are believed to be a common health issue in India, as it is worldwide. However, there is a paucity of data on the knowledge, awareness, and practices (KAP) among these patients. Materials and methods: A crosssectional study was conducted in a medical college of Meerut, Uttar Pradesh. Total 200 patients were evaluated during the period from 2011 to 2012. Results: Total 200 patients with thyroid swelling were evaluated. Sixty percent patients did not know that thyroid is a normal gland in body while 50% did not knew about hyper/hypothyroidism. There are many misconceptions regarding thyroid disorders, such as 79.5% patients thought that hypothyroidism causes excessive weight gain. Conclusion: This study shows that patients with thyroid disorders lack knowledge. Education should take place at all levels and should include doctors and decision makers, health workers, and citizen groups. The results of this study will help the physician to concentrate on these specific issues during their interaction with the patients.

Keywords: Thyroid, hypothyroidism, knowledge, awareness, practices

T

hyroid disorders are very common in India.1 This study was conducted because of the observation by clinical staff that there was lack of knowledge and many misconceptions regarding thyroid gland and its disorders. We conducted a study to assess the knowledge, awareness, and practices among patients with thyroid disorders (Table 1).

Material and Methods A detailed questionnaire was prepared and given to patients who had attended the fine needle aspiration cytology (FNAC) laboratory in the Department of Pathology, LLRM Medical College, Meerut, Uttar

*Senior Resident Dept. of Transfusion Medicine, SGPGIMS, Lucknow, Uttar Pradesh †Assistant Professor Dept. of Community Medicine, Era’s Lucknow Medical College and Hospital Lucknow, Uttar Pradesh ‡Assistant Professor ||Professor §Assistant Professor Dept. of Pathology ¶Professor Dept. of Surgery, LLRM Medical College, Meerut, Uttar Pradesh Address for correspondence Dr Ashutosh Singh Plot No. 35, Dumrao Bagh Colony Assi, Varanasi, Uttar Pradesh-221 005 E-mail: drashullrm@gmail.com

Pradesh, India. Total 200 patients were evaluated during the period from 2011 to 2012. In case of children (juvenile hypothyroidism), the parents of the child were asked to fill up the questionnaire. The patients answered the questionnaire when they were waiting in the FNAC laboratory.

Results In this study, we observed that large number of patients had lack of knowledge about thyroid gland and its disorders. Out of 200 patients, only 120 patients (60%) had correct knowledge that thyroid is a normal gland in neck, while only 100 patients (50%) knew about hyper or hypothyroidism. Number of responses regarding symptoms is given in Table 2.

There are many misconceptions regarding thyroid disorders (Table 3). There were 159 responses (79.5%) for excessive weight gain in case of hypothyroidism.

About 119 patients (59.5%) had no idea about avoidance of cabbage, cauliflowers, and soya in hypothyroidism.

Seventy-four patients (37%) had belief that thyroid medication should be stopped during pregnancy while 80 patients (40%) thought that thyroid medication can be stopped once thyroid tests are normal. Large number of patients (117, i.e., 58.5%) thought that thyroid deficiency could be treated using iodized

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753

ENT Table 1. Knowledge of “Terminologies” Questions

No. of correct responses

No. of incorrect responses

No. response or do not know

“Thyroid” meaning

120 (60%)

72 (36%)

4 (2%)

“Hyper/ Hypothyroidism” meaning

100 (50%)

88 (44%)

12 (6%)

Table 2. Number of People Who Thought the Following Symptoms Were Related to Hyper/Hypothyroidism Question

No. of responses

disorders. These findings are similar to those obtained by previous authors.2,3 Patients should be educated for the various symptoms of thyroid disorders. Patients commonly attribute that any symptom like sore throat in relation to neck is due to thyroid.

Screening for thyroid disorders should be a part of routine health screen in people after the age of 35 years, peri and postmenopausal women, child-bearing women, and in pregnancy and postpartum period.4–7 There is a common misconception of excessive weight gain and obesity with hypothyroidism. In the present study, 79.5% patients thought that hypothyroidism causes excessive weight gain, while it is well known that primary hypothyroidism does not cause an increase in weight of more that 2-3 kg although a symptom of “feeling heavy” is common among patients.8 Patients need to be educated that thyroid medication should not be stopped during pregnancy; apart from iodine deficiency there are immunological causes (Hashimoto’s thyroiditis) resulting in hypothyroidism.

Patients should also be educated for tests for treatment monitoring and long-term nature of treatment.

Weight gain

159

Irregular menstrual cycles

129

Hair fall

112

Sore throat, neck pain, joint pain

105

Depression

99

Voice change

80

Constipation/Diarrhea

79

Skin problems

21

Infertility

15

ÂÂ

Lack of qualified physicians.

No symptoms

5

ÂÂ

Low doctor and patients’ ratio that lead to less time spent by doctors on patients’ education.

ÂÂ

Illiteracy due to which patients are unable to extract information available in electronic and print media.

salt. Seventy patients (35%) had belief in alternative medicine like Yoga, Unani, and Siddha. For treatment monitoring, only 76 patients (38%) had given correct response (Table 4).

Discussion In general, the patients with thyroid disorders had inadequate knowledge of thyroid gland and associated

Factors that contribute to lack of knowledge among patients are the following:

Therefore, an aggressive campaign is required to make the community, health workers, and policy makers aware of the consequences and prevalence of thyroid disorders. The use of local mass media could be considered during the awareness campaigns, since they proved to be effective in increasing the use of iodized salt in Turkey.9 The results of this study will help the

Table 3. Common Misconceptions Regarding Hyper/Hypothyroidism Questions

Yes

No

Do not know

Hypothyroidism causes excessive weight gain

159 (79.5%)

39 (19.5%)

2 (1%)

Cabbages, cauliflowers, and soya should be avoided in hypothyroidism

59 (29.5%)

119 (59.5%)

22 (11%)

Thyroid medications should be stopped during pregnancy

74 (37%)

87 (43.5%)

39 (19.5%)

Thyroid medications can be stopped once thyroid tests are normal

80 (40%)

111 (55.5%)

9 (4.5%)

117 (58.5%)

81 (40.5%)

2 (1%)

70 (35%)

121 (60.5%)

9 (4.5%)

Thyroid deficiency can be treated using iodized salt Alternative medicines can cure thyroid problems

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

ENT practices (KAP) among patients with hypothyroidism attending endocrine clinics of community hospitals in Chennai. Thyroid Res Practice 2010;7:11-5.

Table 4. Knowledge About Treatment Monitoring Responses Correct response

Test for monitoring treatment No.

%

76

38.0

Incorrect response

74

37.0

Do not know

50

25.0

3. Mallik AK, Anad K, Pandav CS, Achar DP, Lobo J, Karmarkar MG, et al. Knowledge, beliefs and practices regarding iodine deficiency disorders among the tribals in Car Nicobar. Ind J Pediat 1998;65:115-20.

physician to concentrate on these specific issues during their interaction with the patients.

Conclusion This study shows that patients with thyroid disorders lack knowledge. Education should take place at all levels and should include doctors, decision makers, health workers and citizen groups. Furthermore, messages regarding thyroid and its disorders should be included in the curriculum of primary schools, secondary schools, high schools, colleges, and universities.

References 1. Desai MP. Disorders of thyroid gland in India. Indian J Pediatr 1997;64:11-20.

2. Kannan S, Mukundan L, Mahadevan S, Sathya A, Kumaravel V, Bhat RV, et al. Knowledge, awareness and

4. Ladenson PW, Singer PA, Ain KB, Baghi N, Bigos ST, Levy EG, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000;160:1573-5.

5. Canadian Task Force on the Periodic Health Examination.

Canadian Guide to Clinical Preventive Health Care.

Ottawa: Canada Communication Group 1994;611-8.

6. AACE Thyroid Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Prac 2002;8:457-69.

7. American College of Obstetricians and Gynaecologists.

Thyroid Disease in Pregnancy. Technical Bulletin no. 37.

Washington, DC: American College of Obstetricians and Gynecologists 2002.

8. ATA Patient Education Web Brochures. Thyroid and weight.

9. Can G, Okten A, Green J. The role of local mass media in promoting the consumption of iodised table salt. Health Educ Res 2001;16:603-7.

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How to Eat Less and Stay Healthy?

Vedic science, Ayurveda, Homeopathy, Naturopathy, Allopathy all talk about eating less to stay healthy.

Following are the ways to eat less: The brain gets a signal that you have eaten only after 20 minutes, therefore, chew every bite of food at least 15 times. It not only provides enough hormones for enzymes but also sends signals to the brain. Therefore, the time spent per meal should be 20 minutes.

The taste buds are only on the tip and side of the tongue. If you gulp food, the brain will not get signals. Eating small pieces and chewing them properly also sends the signals through the taste buds.

The size of the fullness of the stomach also decides how much one can eat. The brain gets signal only when the stomach is 100% full. Therefore, one should not overeat and full the stomach to its size. Also if you eat less and over a period of time the size of the stomach will get shrunken.

Source: eMedinewS

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

755

ENT

Common Ear, Nose, and Throat Problems in Pediatric Age Group Presenting to the Emergency Clinic – Prevalence and Management: A Hospital-Based Study Kalpana Sharma*, Dipen Bhattacharjya†, Himajit Barman‡, Subodh Ch. Goswami||

Abstract ENT-related diseases form a significant portion of ailments in pediatric age group. Many of them present in emergency clinics with acute symptoms requiring urgent management. A prospective study was carried out in the Department of ENT, Gauhati Medical College, Guwahati, Assam, in patients below 16 years of age, to determine the hospital prevalence of ENT emergencies in pediatric age group and their management protocol as followed in a tertiary center. Emergencies relating to ear were most common followed by nasal and pharyngoesophageal conditions. Foreign bodies were most common among aural and nasal emergencies. A considerable number of patients presented with faciomaxillary and orodental injuries. Although mortality is low in such emergency group, morbidity may be very high at times. In management of such emergencies, particularly where operative intervention is required, expertise of an ENT specialist is necessary.

Keywords: ENT emergency, foreign body, injury

P

ediatric population forms a considerable proportion of the total population in our state of Assam. All health-related issues of pediatric age group are considered to be of great importance and these also gives us data for understanding the healthrelated problems and for assessing the health status of a community.

According to the census report 2011, total population of Assam is 31,169,272 out of which 4,511,307 (14.47%) belong to the age group of 0-6 years.1 In Kamrup (rural) district, pediatric population belonging to the age group of 0-6 years forms 12.85% of the population.

The same is 9.56% in Kamrup (metro) district that has a total population of 1,260,419.1 Children frequently suffer from diseases relating to ear, nose, and throat (ENT). Some ENT diseases like acute

*Associate Professor †Postgraduate Trainee ‡Registrar ||Professor Dept. of ENT, Gauhati Medical College, Bhangagarh, Guwahati, Assam Address for correspondence Dr Kalpana Sharma Ashirwad Apartment Basisthapur, Bye Lane No. - 3 (Near Regional Passport Office) Guwahati - 781 028, Assam E-mail: kalpanasharmak@yahoo.co.uk

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suppurative otitis media are more common in children as compared to the adults. The same is the case with adenoid, acute tonsillitis, acute rhinitis of viral origin, acute epiglottitis, and acute laryngotracheobronchitis.

It may be due to various factors like wider and horizontally placed eustachian tube, poorly developed immunity, malnutrition, poor hygiene, overcrowding, lower socioeconomic status of the family, and parental ignorance.2 In addition to attending to outpatient department of a hospital, many children are brought by their parents to the emergency clinic of a hospital with history of ENT-related disease. All of these require urgent management.

In Indian scenario, foreign body (FB) impaction in ENT region are found to be common emergencies and sometimes, they may produce even fatal outcomes.3 It should always be kept in mind that management of ENT emergencies is a specialized job and special instruments and equipments are needed to manage such situations.3 Objective The study was undertaken to determine the hospital prevalence of emergency conditions in children related to ENT. The management protocol as followed in a tertiary center has also been discussed.

ENT Material and Methods A prospective study was conducted in the Dept. of ENT, Gauhati Medical College and Hospital, Guwahati, between July 1, 2011 and June 30, 2012. All patients below 16 years of age were enrolled in the study.

These patients presented to emergency clinics of the department with acute presentation. The patients were examined in detail using bull’s eye lamp, head mirror, otoscope, nasal speculum, and tongue depressor.

The cases with faciomaxillary, orodental injuries, and epistaxis were made to lie down on a couch and were carefully examined under operating light. The cases with impacted aural FBs were examined under operating microscope and all esophageal FB cases were assessed by radiographic examination.

The information that was included in the study is as follows: ÂÂ

Age group

ÂÂ

Male or female preponderance

ÂÂ

Presenting illness

ÂÂ

Number of cases managed on outpatient basis

ÂÂ

Number of cases requiring admission

ÂÂ

Number of cases requiring general anesthesia and operation theater facilities

presented with complaints relating to ear. Eightythree cases (33.06%) presented with problems relating to nose. Twenty-six cases (10.35%) presented with pharyngoesophageal complaints. Forty-seven cases (18.72%) presented with other complaints that included injuries and acute parotitis.

From table 1, it is clear that highest number of cases presented with FB nose, followed by FB ear and injuries. Among the pharyngoesophageal emergencies, the most common was acute tonsillitis followed by FB esophagus. Nasal FBs included plastic beads, pieces of paper, color pencils, pieces of chalk, cereals, grams, seeds of orange, and pieces of rubber.

Aural FBs included plastic beads, foils of chocolates, insects, and rice grains. Among the esophageal FBs, six cases (66.66%) were of coins and one case each was of safety pin, meat bone, and nail. All FBs in throat were impacted fish bone.

Forty-two cases presented with various types of injuries in the faciomaxillary and orodental regions. The causes are mentioned in table 2.

All results were expressed in number and percentage.

Out of 42 cases, 32 (76.19%) were males and 10 (23.80%) were females. Self-fall was exclusively common (76.19%) as a cause of injury; others were results of outdoor sport.

Results

From table 3, it can be seen that most common form of injury was lip laceration and abrasion of maxillary region (80.95%).

A total of 251 patients were examined during this time period. Among these, 155 were males (61.75%) and 96 were females (38.24%). So there is an overall male preponderance. Ninety-five cases (37.84%)

From table 4, it is clear that the disease that was exclusively common in the infants and toddlers was FB esophagus, FB nose, FB ear, otitis externa, and epistaxis.

Some cases of injury were also found in this age group.

Table 1. Presentation of Patients with Various Types of ENT Complaints Diseases FB nose FB ear

Male 29

Female 31

Total Number 60

Percentage (%) 23.90

32

16

48

19.12

Injuries

32

10

42

16.73

Epistaxis

14

9

23

9.16

AOM

13

7

20

7.96

Impacted wax

11

5

16

6.37

Otitis externa

6

5

11

4.38

Acute tonsillitis

8

2

10

3.98

FB esophagus

6

3

9

3.58

FB throat

2

5

7

2.78

Acute parotitis

2

3

5

1.99

FB= foreign body; AOM= acute otitis media.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

757

ENT Table 2. Causes of Injuries in the Faciomaxillary and Orodental Regions Causes of injury

Male

Female

Total number

Percentage(%)

Self fall

23

9

32

76.19

Sport injury

9

1

10

23.80

general anesthesia in operation theater using operating microscope and esophagoscope, respectively. So a total of 42 cases (16.73%) were managed in the operation theater under general anesthesia.

All injuries were repaired carefully. Epistaxis was treated using hemocoagulase solution and application of merocel. Out of 23 cases of epistaxis, six cases

Table 3. Various Types of Injuries Type of injury Lip laceration and abrasion of maxillary region

Male

Female

Total number

Percentage (%)

26

8

34

80.95

Buccal mucosa laceration

0

1

1

2.38

Palatal laceration

1

0

1

2.38

Tongue laceration

1

1

2

4.76

Alveolar injury

3

0

3

77.14

Pinna laceration

1

0

1

2.38

Total

32

10

42

Table 4. Age Wise Distribution of all ENT Emergencies Presenting illness

0-3 years (infants and toddlers)

3-6 years (pre-school age)

6 years and above (school going age)

FB nose

13

47

0

FB Ear

18

30

0

Injuries

6

17

19

Epistaxis

3

11

9

AOM

7

7

6

Impacted wax

1

5

10

Otitis externa

4

5

2

Acute tonsillitis

0

6

4

FB esophagus

8

1

0

FB throat

1

3

3

Acute parotitis

0

1

4

FB = Foreign body; AOM = Acute otitis media.

In the preschool age group, almost all the diseases were found. Injuries were common among school-going children. Wax, FB throat, and acute parotitis were also found in this age group.

All nasal, aural, and pharyngeal FBs were removed under direct vision using good light source. Thirtythree cases (68.75%) of aural FB and all nine cases (100%) of esophageal FB required removal under

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(26.08%) required insertion of merocel. Out of 16 cases of impacted wax, wax was removed in 4 cases (25%) by Jobson Horneâ&#x20AC;&#x2122;s probe, others 12 cases (75%) were prescribed wax dissolver solution followed by removal of wax under microscopic examination.

Cases presenting with acute infection were treated conservatively. Nine cases of esophageal FB, ten cases of epistaxis, and two cases of injury were admitted.

So a total of 21 cases (8.36%) required admission.

ENT No complication was observed in patients treated during this period.

Discussion FBs, animate or inanimate, in external auditory canal and nasal cavity are commonly found in children. It is common especially in young children who tend to insert FBs when they are playing or when they get bored.2 In our study, maximum number of FBs was found in the age group of 0-6 years. It was relatively uncommon in children above 6 years of age. In one previous study carried out by ED Kitcher in 2007,11 the peak age incidence was observed in 0-9 years of age.4 The range of FBs is extensive including food particles, vegetable matter, and inorganic objects like paper, plastic beads, chalks and coins (in esophagus). Aural and nasal FBs are mostly of inanimate type.3 Coin is a common FB that gets impacted in esophagus and it is particularly common in children.3 In our study, all aural and nasal FBs were inanimate and most common esophageal FB was a coin (66.66%).

It was observed that all nasal FBs could be removed using FB hook or Tilley’s forceps. Out of 48 cases of aural FBs, 33 cases (68.75%) required general anesthesia for removal. Skill of an ENT specialist is very necessary for removal of aural FB because unskilled removal of aural FBs may injure eardrum, ossicles, or even facial nerve.3 In one study carried out by Mackle et al,4 it was found that although 65% of nasal FBs can be removed in emergency clinics, but it was not so in the case of aural FBs, 96% of which required removal under anesthesia and skill of an ENT surgeon.4 In our study, 68.75% of aural FBs required operation theater facilities and general anesthesia for their removal.

All esophageal FBs need urgent esophagoscopy and removal under general anesthesia. Esophagoscopy is a difficult procedure, especially when tried by unskilled person. Fatal accident can occur by slightest trauma due to thinness of esophageal wall.3 In our study, a considerable number of cases presented with faciomaxillary and orodental injuries, most of which were result of self-fall (76.19%). All types of injuries were common in males over 76.19%. Most common injury that was found in our study was laceration of lip and abrasion of maxillary region (80.95%), and highest incidence was observed in the age group of school-going children (6 years and above).

In a previous study conducted by Khan5 on ENT injuries in children, highest incidence was observed in the age group of 10-15 years with a male preponderance.

It was probably due to more outdoor activities on the part of males. Most common etiology was self-fall (32%) and nasal bone fracture was the most common type of injury.5 ENT injuries in children can give rise to facial deformities and in the long run, it can create functional, cosmetic, and psychological problems.

In developing countries like India, most of the deaths below 5 years of age is due to communicable diseases, respiratory infection, and diarrhea and very few are due to injuries.6 But injuries should always be treated well as it is an avoidable cause of disability.7 Acute infection of various sites in ENT is one of the commonest causes of emergencies in children.

In our study, the cases that were found are acute otitis media (AOM), otitis externa, acute tonsillitis, and acute parotitis. Among these, AOM was a presenting illness in highest number of cases. The incidence was more or less same in all groups as far as our study is concerned. AOM is common in infants due to wider and horizontally placed Eustachian tube and it comprises of one third of problems seen in the pediatric practice during first 5 years of life.8 It is recommended that there is a need for otosopic examination of all pyretic children as the resultant hearing loss due to acute suppurative otitis media is related to difficulties in language acquisition in children below 2 years of age. It also affects literacy and school achievements.

Conclusion ENT emergencies in pediatric age group are not uncommon. Mortality is low, but a numbers of complications may arise that may include perforation of drum, aspiration, airway obstruction, and long-term complication like nasal and facial deformity. Therefore, proper management of ENT emergencies is of utmost importance. Most common ENT emergency in pediatric age group is FBs that can be removed and patients can be disposed on outpatient basis. As operative intervention is required in a significant number of ENT emergencies, expertise of an ENT specialist is necessary in management of these cases.

References 1. Census of Assam 2011. Available at: http://www.assam.gov.in 2. Logan Turner’s Diseases of Nose, Throat and Ear, 10th edition. In: Maran AGD. New York: Elsevier 1988:p464.

3. Saha S, Chandra S, Mondal PK, Das S, Mishra S, Rashid MA, et al. Emergency otorhinolaryngological cases in medical college, kolkata – a statistical analysis. Indian J Otolaryngol Head Neck Surg 2005;57(3):219-25.

4. Mackle T, Conlon B. Foreign body in nose and ears in children: should these be managed in accident and

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ENT emergency setting. Int J Pediatr Otorhinolaryngol 2006;70(3):425-8.

5. Khan AR. Dept. of ENT, Khyber Teaching Hospital, Pakistan, Ear nose and throat injuries in children. J Ayub Med Coll Abbottabad 2005;17(1):54-6.

6. Agarwal V, Gupta A. Accident poisoning in children.

Indian Paeds J 1974;11:617-21.

7. Singh I, Gathwala L, Gathwala G, Yadav SPS. Ear nose and throat injuries in children. Pak J Otolaryngol 1993;9:133-5.

8. Pestalozza G, Romagndi M, Tessetore E. Incidence and risk factor of acute otitis media in children of different age group. Adv Otolaryngol 1988;40:47-56.

9. Alabi BS, Abdulkarim AA, Fatai U, Abdul Majeed SO. Prevalence of acute otitis media among children with pyrexia. Auris Nasus Larynx 2009;36(5):532-5.

10. Ngo A, Ng KC, Sim TP. Otorhinolaryngeal foreign bodies in children presenting to emergency department. Singapore Med J 2005;46(4):172-8.

11. Kitcher ED, Janger A, Baidoo K. Emergency ear, nose and throat admission at Korle-Bu Teaching Hospital. Ghana Med J 2007;41(1):9-11.

12. AI-Mazrou, et al. Surgical emergencies in pediatric otolaryngology. Saudi Med J 2009;30(70):932-6.

13. Mohan D. Children injuries in India – extent of problem and strategies for control. Indian J Paed 1986;53:607-15.

14. Ghose P. Foreign bodies in ear, nose and throat (prediction and management). Indian J Otolaryngol 1999;51(1):2-5.

15. Bernius M, Perlin D. Paediatric ear, nose and throat emergencies. Pediatr Clin North Am 2006;53(2):195-214.

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Talking on Mobiles May be Harmful We do not see sparrows and crows any more.

Mobile phones radiations and towers poses serious health risks, including loss of memory, lack of concentration, disturbance in the digestive system and sleep disturbances.

An inter–ministerial 8 member committee formed by the ministry of communications and information technology to study the hazards posed by mobile phones attributed the disappearance of butterflies, bees, insects and sparrows vanishing from big cities to mobile phone–related radiation. The committee included representatives from the health ministry, Department of Biotechnology and Member Secretary, DoT. The recommendations of the committee are: ÂÂ Mobile phones not adhering to standard levels of specific absorption rate (SAR) – a measure of the amount of radiofrequency energy absorbed by the body while using a phone –– should be barred. ÂÂ Mobile towers should not be installed near high density residential areas, schools, playgrounds and hospitals. ÂÂ The localized SAR value as per the Indian guidelines standard is 2 watt per kg, averaged over a six minute period and using a 10 gram average mass. ÂÂ With higher SAR values of mobile handsets the public could potentially receive much higher radiofrequency exposure. ÂÂ In the case of a person using a cellphone, most of the heating occurs on the surface of the head, causing its temperature to increase by a fraction of a degree. The brain blood flow is capable of disposing this excess by increasing the local blood flow and increasing body temperature. ÂÂ Non–thermal effects of cellphone use – attributed to the induced electromagnetic effects inside the body’s biological cells – are more harmful. ÂÂ People who are chronically exposed to low-level wireless antenna emissions and users of mobile handsets have reported feeling several unspecific symptoms during and after its use, ranging from burning and tingling sensation in the skin of the head, fatigue, sleep disturbances, dizziness, lack of concentration, ringing in the ears, reaction time, loss of memory, headache, disturbance in digestive system and heart palpitation. ÂÂ Compared to Europeans, Indian cellphone users are more at risk for adverse affect of radiation due the country’s hot tropical climate, low body mass index, and low fat content. ÂÂ Exposure to radiation from mobile towers and mobile phones could have an adverse impact on male fertility and pose health hazards by depleting the defence mechanism of cells.

Source: TOI

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Neurology

Complex Regional Pain Syndrome Type 1 Treated with Vitamin C SB Gondhali*, SH Bhattad†, G Nanoti‡, H Dua||, B Asudani§

Abstract Complex regional pain syndrome, formerly reflex sympathetic dystrophy or causalgia, is a chronic progressive disease characterized by severe pain, swelling, and changes in the skin. It often affects an arm or a leg and may spread to another part of the body and is associated with dysregulation of the autonomic nervous system resulting in multiple functional loss, impairment, and disability. It occurs mostly in adolescence. Although treatment is often unsatisfactory, we report a young girl treated satisfactorily with vitamin C.

Keywords: Complex regional pain syndrome, autonomic nervous system, vitamin C

T

he condition currently known as complex regional pain syndrome (CRPS) was originally described during the American Civil War by Silas Weir Mitchell, who is sometimes also credited with inventing the name “causalgia,”1 also known as reflex sympathetic dystrophy (RSD). It is a chronic progressive disease characterized by severe pain, swelling, and changes in the skin. It often affects an arm or a leg and may spread to another part of the body; it is associated with dysregulation of the autonomic nervous system resulting in multiple functional loss, impairment, and disability. It is usually seen in adolescent girls but has been described in children.2,3 Vitamin C may have a therapeutic role related to its antioxidant properties; vitamin C deficiency has not been implicated as cause of CRPS. We are reporting scurvy and CRPS in the same patient.

Case Report A 3-year-old female child presented with inability to walk, pain in both lower limb, and was bedridden since 6 months. After a minor accident, the patient developed

*Assistant Professor †Professor Dept. of Paediatrics, MIMSR Medical College, Latur, Maharashtra ‡Associate Professor ||Assistant Professor §Assistant Lecturer Dept. of Paediatrics, NKP Salve Institute of Medical Sciences and Research Centre, and Lata Mangeshkar Medical College, Nagpur, Maharashtra Address for correspondence Dr Shital Bhattad Gondhali Dept. of Paediatrics, MIMSR Medical College, Latur, Maharashtra

swelling of both knees and ankles; she had excessive pain when touched lightly and there was excessive sweating. Diet was adequate in proteins and calories.

Developmental milestones were normal.

On examination, the patient was conscious, irritable, and the vitals were stable. Patient had pallor with bleeding spongy gums along with petechiae and hyperkeratosis on lower limbs. There was no lymphadenopathy or hepatosplenomegaly. Central nervous system examination revealed normal tone, power and reflexes in all limbs. There was hyperesthesia in both lower limbs.

On local examination, she was not moving her lower limbs; both lower limbs were in flexed attitude.

Temperature of the swollen part was raised.

As given in the Gerald Fenichel’s Clinical Pediatric Neurology, we immersed the affected limbs in warm water. Wrinkling of the skin of toes was absent as compared to wrinkling of hands. As wrinkling of fingers and toes requires intact sympathetic innervation, this manner was helpful in diagnosing.

Hemoglobin was 6 g/dL, TLC was 11,000/mm3, and platelet count was 6,12,000/mm3. Peripheral smear revealed microcytic, hypochromic anemia; there were no abnormal cells. CPK and VDRL were normal. X-ray of the hip and knee joints revealed pencil-thin cortex, decreased bone density, and white line of Frankel, suggestive of scurvy. A provisional diagnosis of scurvy and CRPS type 1 was made.

Hundred milligram of oral vitamin C was given daily.

Hyperesthesia started improving and the child was able

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

761

Neurology to walk with support within 15 days of treatment. After 1 month duration, she started walking independently and was perfectly normal.

Discussion CRPS, formerly RSD or causalgia, is a chronic progressive disease characterized by severe pain, swelling, and changes in the skin. It often affects an arm or a leg and may spread to another part of the body; it is associated with dysregulation of the autonomic nervous system resulting in multiple functional loss, impairment, and disability. Although treatment is often unsatisfactory, early multimodal therapy can cause dramatic improvement or remission of the syndrome in some patients.4 The International Association for the Study of Pain has proposed dividing CRPS into two types based on the presence of nerve lesion following an injury. ÂÂ

ÂÂ

Type I, formerly known as RSD, Sudeck’s atrophy, reflex neurovascular dystrophy, or algoneurodystrophy, does not have demonstrable nerve lesions.

Type II, formerly known as causalgia, has evidence of obvious nerve damage.

CRPS can strike at any age, but the mean age of diagnosis is 42.5 CRPS has been diagnosed in children as young as 2 years old.6 It affects both men and women; however, CRPS is three times more frequent in females than males.5 The number of reported CRPS cases among adolescents and young adults is increasing.7 There may be bilateral involvement.2 The pathophysiology of CRPS remains uncertain.

It may be due to sympathetic dysfunction, central dysfunction, or an inflammatory process. However, recent research has suggested that oxidative damage (e.g., by free radicals) may play a role.5 The International Association for the Study of Pain (IASP) lists the diagnostic criteria for CRPS I (RSDS) as follows: ÂÂ

The presence of an initiating noxious event or a cause of immobilization.

ÂÂ

Continuing pain, allodynia (perception of pain from a nonpainful stimulus), or hyperalgesia (an exaggerated sense of pain) disproportionate to the inciting event.

ÂÂ

Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the area of pain.

ÂÂ

The diagnosis is excluded by the existence of any condition that would otherwise account for the degree of pain and dysfunction.

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

The IASP criteria for CRPS I diagnosis has shown a sensitivity ranging from 98% to 100% and a specificity ranging from 36% to 55%. As per the IASP guidelines, interobserver reliability for CRPS I diagnosis is poor.

Two other criteria used for CRPS I diagnosis are Bruehl’s criteria and Veldman’s criteria that have moderate-togood interobserver reliability. In the absence of clear evidence supporting one set of criteria over the others, clinicians may use IASP, Bruehl’s, or Veldman’s clinical criteria for diagnosis. While the IASP criteria are nonspecific and possibly not as reproducible as Bruehl’s or Veldman’s criteria, they are cited more widely in the literature including treatment trials.8 According to Veldman et al,5 diagnosis of CRPS can be made clinically based on the following: ÂÂ

At least four of the five symptoms and signs are present: unexplained diffuse pain, altered skin color, altered skin temperature, edema, and reduced active range of movements.

ÂÂ

Symptoms aggravated by activity of the extremity.

ÂÂ

Symptoms present in an area much larger than and distal to the area primary injury.

All these features were seen in our patient. The International Association for Study of Pain criteria are also similar, with electromyography (EMG) and nerve conduction velocity (NCV) required to distinguish between type 1 and 2, although the clinical validation of these criteria are still debated.2 Veldman’s criteria are most widely used.

No specific test is available for CRPS and diagnosis is primarily through observations of symptoms. However, thermography, sweat test, X-ray, and sympathetic blocks can be used to build a picture of the disorder.9 EMG/NCV can help differentiate early phases of CRPS type 2. Scintigraphy and bone scan have a sensitivity of 72% and 50%, respectively.10,11 Absence of abnormal tests does not preclude diagnosis of CRPS. Early diagnosis is the mainstay of successful treatment of RSD. Management consists of physiotherapy, sympathetic blocks, epidural blocks, drug treatment (alpha blockers, calcium channel blockers, NSAIDs, calcitonin, corticosteroid and antidepressants) and surgical sympathectomy.12,13 Vitamin C could have some efficacy related to its antioxidant properties. One double-blind study showed that vitamin C given to patients with wrist fractures reduced the incidence of CRPS.14 In two placebo-controlled randomized clinical trials, Zollinger et al14 showed that 500 mg vitamin C daily

Neurology reduces the chance for the occurrence of CRPS after wrist fractures.14 In teens and younger patients with CRPS, the prognosis is excellent. Most of the patients improved markedly without invasive therapy; 75% of children had full recovery. Long-term sequalae include shortening of limbs or foot because of prolonged immobilization and osteoporosis.5 Since our patient had showed response to vitamin C administration, there might be some association between scurvy and CRPS. References 1. Mitchell SW. Injuries of Nerves and their Consequences.

Philadelphia: JB Lippincott 1872.

dystrophy: prospective study of 829 patients. Lancet 1993;342(8878):1012-6.

6. Güler-Uysal F, Başaran S, Geertzen JH, Göncü K. A 2½-year-old girl with reflex sympathetic dystrophy syndrome (CRPS type I): case report. Clin Rehabil 2003;17(2):224-7.

7. RSDSA: Reflex Sympathetic Dystrophy Syndrome Association. Available at: http://www.rsds.org.

8. Quisel A, Gill JM, Witherell P. Complex regional pain syndrome underdiagnosed. J Fam Pract 2005;54(6):524-32.

9. Sandroni P, Low PA, Ferrer T, Opfer-Gehrking TL, Wilson PR. Complex regional pain syndrome: prospective study and laboratory evaluation. Clin J Pain 1998;14:282-9.

10. Intenzo C, Kim S, Millin J, Park C. Scintigraphic patterns of reflex sympathetic dystrophy syndrome in lower extremities. Clin Nucl Med 1989;14:657-61.

2. de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC. The incidence of complex regional pain syndrome: a population-based study. Pain 2007;129:12-20.

11. Werner R, Davidcoff G, Jackson HD, Cremer S, Ventocilla C, Wolf L. Factors affecting the sensitivity and specificity of the three phase bone scan in the diagnosis of reflex sympathetic dystrophy in the upper extremity. J Hand Surg (Am) 1989;14:520-3.

3. Bant A, Hurowitz B, Hassan N, Du VT, Nadir A. Complex regional pain syndrome (reflex sympathetic dystrophy) in a patient with essential mixed cryoglobulinemia and chronic hepatitis C. J Pak Med Assoc 2007;57:96-8.

12. Eisenberg E, Geller R, Brill S. Pharmacotherapy options for complex regional pain syndrome. Expert Rev Neurother 2007;7:521-31.

4. Neuropathic pain. Merck Manual for Healthcare Professionals. Available at: http://www.merckmanuals. com/professional/ 5. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic

13. Low AK, Ward K, Wines AP. Pediatric complex regional pain syndrome. J Pediatr Orthop 2007;27:567-72.

14. Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? J Bone Joint Surg Am 2007;89:1424-31.

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Never Leave the Mind Vacant ÂÂ

ÂÂ

An empty mind is the devil’s workshop. All evil actions start in the vacant mind. Keep your mind occupied in something positive, something worthwhile. Actively follow a hobby. Do something that holds your interest.

You must decide what you value more: money or peace of mind. Your hobby, like social work or temple work, may not always earn you more money, but you will have a sense of fulfillment and achievement.

Even when you are resting physically, occupy yourself in healthy reading or mental chanting of God’s name.

Source: emedinews

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Obstetrics and Gynecology

A Case Report on Female Pseudohermaphroditism: An Ambiguous Genitalia K Tabassum*, M Zulkifle†, Yasmeen‡, M Nasar§

Abstract Ambiguous genitalia is a birth defect of the sex organs that makes it unclear whether an affected newborn is a girl or a boy.

This condition occurs approximately 1 in every 4,500 births that causes gynecological and obstetrical problems. Defects of the external genital organs (penis, testes, or clitoris) usually result from abnormal levels of sex hormones in the fetus before birth.

A 30-year-old primi with 38 weeks of pregnancy was admitted on August 21, 2011 at 8.45 PM with complaints of mild lower abdominal pain. Ultrasound scan on the same day showed a single 38 weeks live intrauterine fetus of ambiguous genitalia with breech presentation. Emergency lower segment cesarean section was performed on August 22, 2011 at 10.55 PM and the patient delivered a baby with ambiguous genitalia having both clitoris and penis. This diagnosed to be a case of female pseudohermaphroditism caused by congenital adrenal hyperplasia because babies who are born with ambiguous genitalia having external genital organs that do not appear clearly male or female or have features of both, but have female internal reproductive organs are known as female pseudohermaphrodities.

Keywords: Primi, Breech presentation, ambiguous genitalia, diagnosis and emergency LSCS

A

mbiguous genitalia, also known as a typical genitalia are birth defects or birth variations of the sex organs that makes it unclear whether an affected newborn is a girl or a boy. This condition occur approximately 1 in every 4,500 births, which causes gynecological and obstetrical problems. Defects of the external genital organs (penis, testes, or clitoris) usually result from abnormal levels of sex hormones in the fetus before birth. Congenital adrenal hyperplasia and chromosomal abnormalities commonly cause genitalia defects. Other cause includes genetic variation, hormonal imbalance, and enzyme deficiency.

Babies who are born with ambiguous genitalia having external genital organs that do not appear clearly male or female or have features of both, but have female internal reproductive organs, are known as female pseudohermaphrodities. It refers to the gonadal sex, that is, ovaries.1,3

*Reader Dept. of Obstetrics and Gynecology †Head Dept. of Preventive Medicine, National Institute of Unani Medicine, Bangalore ‡DMO Sameena Maternity Nursing Home, Hyderabad §Lecturer Dr Abdul Haq Unani Medical College, Kurnool, Andhra Pradesh Address for correspondence Dr K Tabassum Dept. of Ostetrics and Gynecology National Institute of Unani Medicine, Bangalore, Karnataka E-mail: drtabassum.nium@gmail.com

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Congenital adrenal hyperplasia (CAH) is a metabolic disorder caused by a defect in an enzyme (21 hydroxylase) involved in the steroid hormone synthesis in the adrenal gland. CAH is inherited by an autosomal recessive disorder. It involves an enzyme deficiency that causes the adrenal glands to produce excess amounts of male hormones (androgens) that results in masculinized female external genitalia. The excess androgens can cause the clitoris to grow too large resembling a penis. A severe form of the disorder can affect kidney function and may cause death also.

Individuals with CAH require lifelong treatment with the missing hormones. Affected girls may require surgery to correct the appearance of the external genitalia.2,3 Case Report A 30-year-old primi with 38 weeks pregnancy was admitted on August 21, 2011 at 8.45 PM in the maternity ward of our hospital. She had mild lower abdominal pain since last night but had no history of bleeding or draining per vagina. She had been married for 3 years and there was no history of consanguinity.

Patient had no issues and she conceived after infertility treatment. Ultrasound scan report on August 22, 2011 showed a single 38 weeks live intrauterine fetus of ambiguous genitalia with breech presentation. Testes could not be located in the labioscrotal region/inguinal region bilaterally. Urinary bladder was distended. No definite evidence of uterus could be made out. Corpus

Obstetrics and Gynecology spongiosum and corpus cavernosum could be made out. There was no definite evidence of vaginal mucosal line. The fetal heart rate was 158 beats/min and her expected date of delivery was August 31, 2011. With these ultrasonographic findings, it was diagnosed as a case of CAH.4 On admission, her hemoglobin was 9.9 g% and blood group was found to be O positive. The vitals were recorded hourly and first readings on admission were recorded as blood pressure 110/70 mmHg, pulse 98/min, regular. Temperature was normal. Systemic clinical examination was clear. Per abdomen, height of uterus was 38 weeks and fetal heart sounds were clear. Emergency lower segment cesarean section was done on August 22, 2011 on 10.55 PM and the patient delivered a live baby of weight about 2.15 kg with abnormal genitalia having both clitoris and penis (Fig. 1 (a-d)). The patient was monitored after delivery and her condition was stable.4 Discussion There are different types of ambiguous genitalia that include the babies with ovaries and testicles and the

external genitalia are neither clearly male nor female or the baby has ovaries and a penis-like structure or phallus or has undescended testes and external female genitals including the vulva. In this case, the external genitalia were unclear, whether male or female. The baby had both features, characterized by a large (penis-like) clitoris with undescended testis.

It could be due to excess androgen secretion during pregnancy. Excess of this male hormone affected the babyâ&#x20AC;&#x2122;s genital development. CAH involves deficiency of an enzyme that causes the adrenal glands to produce excess amounts of male hormone (androgen) that results in masculinized female external genitalia. The excess androgen can cause the clitoris to grow too large resembling a penis. A severe form of the disorder can affect kidney function and may cause death also.

Individual, with CAH requires lifelong treatment with the missing hormones. Affected girls may require surgery to correct the appearance of the external genitalia. The chromosomal study was not yet done.

On the basis of the above suggesting feature, this entity could be a case of female pseudohermaphroditism caused by congenital adrenal hyperplasia.

a

b

c

d

Figure 1 a-d. Ambiguous genitalia having both clitoris and penis.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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Obstetrics and Gynecology If the child is assigned female gender then surgery is performed to create genitals appearing like females.

This surgery can include reduction of the clitoris, formation or repair of vagina (vaginoplasty), and repair of the urethra.

Conclusion Ambiguous genitalia is a birth defect or birth variation of the sex organs that makes it unclear whether an affected newborn is a girl or a boy. This condition occur approximately 1 in every 4,500 births, which causes gynecological and obstetrical problems. The excess androgen can cause the clitoris to grow too large resembling a penis. A severe form of the disorder can affect kidney function and may cause death also.

Individual with CAH require lifelong treatment with the missing hormones. Affected girls may require

surgery to correct the appearance of the external genitalia.

Acknowledgment The author would like to thank Dr Sameena, Dr Shakeela, and Dr Khusro for their continuous encouragement and guidance in preparation of this manuscript and for permitting us to use the hospital data.

References 1. Howkins and Bourne Shaw’s Text Book of Gynaecology, 10th edition. 1991:96-8.

2. Dutta DC. Text Book of Obstetrics and Gynecology, 5th edition. 2001:439.

3. Jeffcoate N. Principles of Gynaecology, 4th edition.

London, Boston: Butterworths 1975:159-62.

4. Sameena Maternity Nursing Home, D.No.18-3-193/18/A, Talab Katta, Yakhutpura, Hyderabad.

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Tobacco, Drug Use in Pregnancy Can Double Risk of Stillbirth Smoking tobacco or marijuana, taking prescription painkillers, or using illegal drugs during pregnancy is associated with double or even triple the risk of stillbirth, according to research funded by the National Institutes of Health.

Researchers based their findings on measurements of the chemical by-products of nicotine in maternal blood samples.

“Smoking is a known risk factor for stillbirth, but this analysis gives us a much clearer picture of the risks than before,” said senior author Uma M. Reddy, M.D., MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that supported the study. “Additionally, results from the latest findings also showed that likely exposure to second hand smoke can elevate the risk of stillbirth.” Stillbirth occurs when a fetus dies at or after 20 weeks of gestation.

The researchers tested the women’s blood for cotinine, a derivative of nicotine, and tested fetal umbilical cords for evidence of several types of drugs. They looked for evidence of the stimulants cocaine and amphetamine; prescription painkillers, such as morphine and codeine, and marijuana. These tests reflect exposure late in pregnancy. Among the women who had experienced a stillbirth, more than 80 percent showed no traces of cotinine and 93 percent tested negative for the other drugs. In comparison, about 90 percent of women who gave birth to a live infant tested tobacco– free and 96 percent tested negative for other drugs. Based on the blood test results and women’s own responses, the researchers calculated the increased risk of stillbirth for each of the substances they examined: ÂÂ Tobacco use: 1.8 to 2.8 times greater risk of stillbirth, with the highest risk found among the heaviest smokers ÂÂ Marijuana use: 2.3 times greater risk of stillbirth ÂÂ Evidence of any stimulant, marijuana or prescription painkiller use: 2.2 times greater risk of stillbirth ÂÂ Passive exposure to tobacco: 2.1 times greater risk of stillbirth The researchers noted that they could not entirely separate the effects of smoking tobacco from those of smoking marijuana.

Only a small number of women tested positive for prescription painkiller use, but there was a trend towards an association of these drugs with an elevated stillbirth risk.

Source: eMedinewS

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Ophthalmology

Management of a Complicated Case of Symblepharon with Amniotic Membrane Transplantation P Jain*, JP Chughâ&#x20AC;

Abstract Amniotic membrane transplantation (AMT) has gained widespread acceptance in various ocular diseases. Its anti-inflammatory activity and close resemblance to conjunctival epithelium has propagated it as an ideal substitute for ocular surface reconstruction.

Here is a case report of a complicated case of recurrent symblepharon and ankyloblepharon after fire cracker injury that was managed successfully with AMT with excellent cosmetic results.

Keywords: Amniotic membrane transplantation, symblepharon, ankyloblepharon

CASE HISTORY A 12-year-old boy presented to us with the cosmetic disfigurement and difficulty in opening right eye associated with watering since the past 2 years after fire cracker injury in the same eye. Before presenting to us, he had already undergone symblephrectomy once somewhere else followed by recurrence one month after surgery. On examination, recorded Snellen acuity was 20/20 in both eyes. Medial ankyloblepharon was present involving upper and lower lacrimal puncta along with symblepharon involving nasal side of the bulbar conjunctiva in the right eye [Fig. 1 (a) and (b)].

There was restricted abduction and elevation of the same eye. Rest of the ocular examination was within normal limits. Lid and ocular surface reconstruction after symblepharectomy along with medial canthoplasty was done using fresh amniotic membrane under general anesthesia [Fig. 2 (a)-(g)]. Lacrimal puncta could not be identified after excision of fibrous tissue. Hence, lacrimal drainage apparatus was not reconstructed in the same sitting. The patient was prescribed topical steroids,

a

â&#x20AC; Senior

Professor Regional Institute of Ophthalmology Post Graduate Institute of Medical Sciences Rohtak, Haryana Address for correspondence Dr Prachi Jain MBBS Post Graduate Institute of Medical Sciences Rohtak, Haryana

b

Figure 1. Preoperative image showing medial (a) ankyloblepharon and (b) symblepharon.

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Ophthalmology

a

b

c

d

e

f

g

Figure 2. Surgical steps. (a) Laterally rotated eyeball showing thickened conjunctival fold along with medial ankyloblepharon and symblepharon. (b) Thickened conjunctival fold excised. (c) Ankyloblepharon and symblepharon released. (d) Lid margin reconstruction. (e) Raw area covered with amniotic membrane. (f) End of surgery. (g) Conformer in situ.

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Figure 3. Six months postoperative image showing excellent cosmetic restoration and no evidence of recurrence.

Ophthalmology antibiotics, and lubricating eye drops postoperatively.

Follow-up was done for 6 months postoperatively.

There was no evidence of recurrence after 6 months of surgery with good cosmetic results (Fig. 3).

DISCUSSION Amniotic membrane is the innermost layer of placenta with various beneficial properties. It is now widely used in the treatment of nonhealing corneal ulcers, persistent epithelial defects, and ocular surface reconstruction. Histologically, it closely resembles the basement membrane of conjunctiva.1 It has inhibitory effect on various inflammatory cytokines like interleukin (IL)-1a, IL-2, IL-8, IFN-γ, TNF-β, and platelet-derived growth factor that imparts antiinflammatory properties to it.2 It prevents epithelial scarring by inhibiting TGF-β signaling thereby preventing myofibroblastic differentiation of corneal and conjunctival fibroblasts.3 These properties make it an ideal substitute for ocular surface reconstruction following chemical injuries, cicatricial ocular surface disorders, pterygium, and ocular

surface growth excisions. It promotes epithelization of raw surfaces and therefore prevents recurrence of symblepharon.

All these properties helped in preventing recurrence of the complicated symblepharon and ankyloblepharon along with good ocular surface restoration in our case.

REFERENCES 1. Fukuda K, Chikama T, Nakamura M, Nishida T. Differential distribution of sub-chains of the basement membrane components type IV collagen and laminin among the amniotic membrane, cornea and conjunctiva.

Cornea 1999;18:73-9.

2. Solomon A, Rosenblatt M, Monroy D, Ji Z, Pflugfelder SC, Tseng SC. Suppression of Interleukin 1 alpha and Interleukin 1 beta in the human limbal epithelial cells cultured on the amniotic membrane stromal matrix. Br J Ophthalmol 2001;85:444-9.

3. Lee SB, Li DQ, Tan DT, Meller DC, Tseng SC. Suppression of TGF β signaling in both normal conjunctival fibroblasts and pteryigial body fibroblasts by amniotic membrane.

Curr Eye Res 2000;20:325-34.

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Fenofibrate in Diabetic Retinopathy Fenofibrate to slow the progression of existing diabetic retinopathy in people with type 2 diabetes has been approved

by FDA in Australia. As per the new findings fenofibrate has a major beneficial effect on eye disease and disability as per Anthony Keech, MD, professor of medicine, cardiology, and epidemiology at the University of Sydney.

He stressed the importance of treating it early, before the condition worsens to the point of needing laser surgery.

Laser surgery is very effective at preventing retinal hemorrhages but destroys the treated retina. Early treatment also helps prevent the need for intraocular injections of anti–(vascular endothelial growth factor) VEGF drugs and associated risks.

Diabetic retinopathy is the most common cause of vision loss in adults of working age with more than 50% of people with type 2 diabetes having retinopathy after 10 years of disease. Without effective treatment, 10% of patients will have severe visual impairment after 15 years of diabetes and will be unable to read or drive a car, and around 2% will be legally blind.

Source: eMedinewS

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Orthopedics

Hansen’s Arthritis: An Overlooked Entity Aashish Shejpal

Abstract Leprosy, a chronic granulomatous infection caused by Mycobacterium leprae, classically presents with cutaneous and neurological manifestations. Musculoskeletal involvement, though third most common presentation, is underdiagnosed and underreported. It may manifest in the form of Charcot’s arthropathy, acute symmetrical polyarthritis or swollen hands and feet syndrome during lepra reactions, insidious-onset chronic symmetrical polyarthritis mimicking rheumatoid arthritis (RA) or as isolated tenosynovitis or tenosynovitis associated with arthritis or neuropathy. At times, articular involvement may be the sole presenting manifestation even without cutaneous lesions. Other rheumatological manifestations occasionally reported are enthesitis, sacroiliitis, cryoglobulinemic vasculitis and DM. Delay in diagnosis and management may be detrimental and may result in deformities and loss of function. This case report aimed at presenting a comprehensive clinical scenario of various rheumatological manifestations of leprosy to sensitize rheumatologists and physicians across the continents.

Keywords: Leprosy, mycobacterium leprae, charcot’s arthropathy, articular involvement, rheumatological manifestations Case Report History A 48-year-old male patient, a textile industry worker, recently detected case of diabetes mellitus type 2 came with chief complaints of pain and swelling over both wrist joints since 1 month and generalized weakness since 15 days. Pain and swelling over both wrist joints was on and off and there was history of morning stiffness which lasted for 2 hrs and stiffness eased with physical activity. There was also history of pain and swelling over bilateral knee joints. Patient had positive family history of Hansen’s disease.

Figure 1. Swelling over both hands and edema fat

Examination Vitals stable, bilateral pitting edema feet +, swelling with marked limitation of movement of hands and knee joints (Figs. 1-3).

Bilateral ulnar nerves thickened, no other nerve thickened, no evidence of hypopigmentation.

Fundus examination: background retinopathy.

CVS,RS,P/A =WNL CNS = Deep tendon reflexes depressed, joint position and vibration impaired, touch pain and temperature sensation intact.

Address for correspondence Dr Aashish Shejpal E-mail: aashish.shejpal@gmail.com

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Figure 2. Swelling over both hands

Orthopedics

Figure 3. Swelling over both knee joints

Figure 5. Lepra bacill (solid arrow).

Nerve conduction test: Sensory motor polyneuropathy.

Nerve biopsy = epitheloid and dense mononuclear inflammatory infiltrate seen (Fig. 4) Fite faraco stain = lepra bacill seen (Fig. 5) Treatment

Figure 4. Epitheloid cells (solid arrow) and mononuclear inflammatory infiltrate (dashed arrow).

During hospital stay patient developed nasal cellulitis, which drained 20 cc pus.

Investigations ESR = 52 mm, CBC,PS,KFT = WNL. RA factor, ANA (immunofluoroscence), Anti CCP = negative.

CRP = positive.

24 h urine protein = 56 mg/24 h Thyroid profile = WNL USG abdomen = WNL Skin clipping = no AFB seen,

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Doses of insulin

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Cap rifampicin 600 mg once a month, tab dapsone 100 mg HS,cap clofazimine 50 mg OD for 12 months

ÂÂ

Etorocoxib

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Supportive treatment

Discussion Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae with predominant involvement of skin, nerves and eyes.1 The introduction of multidrug therapy in 1988 has reduced the burden of disease considerably except in a few countries.2 As of June 2006, the prevalence in India is 0.84 per 10,000, but nine states/union territories of the country still have not achieved the elimination target of the World Health Assembly.3 India is considered to be the epicentre of the problem; in 2004, 2,60,000 of the 4,08,000 people diagnosed across the world were found to be residing in India.

The classical presentation of leprosy is in the form of hypersthetic/anesthetic, anhidrotic macules, patches, plaques or papulonodular lesions. Neural involvement can manifest as paresthesias or as

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Orthopedics sensorimotor mononeuropathy, mononeuritis multiplex or polyneuropathy. Articular involvement in leprosy has been recognized since 600 B.C. in Chinese literature.5 The two most common and well-recognized forms of articular involvement, neuropathic joints and post-traumatic septic arthritis occur as a consequence of neuropathy.6,7 In recent times, primary articular involvement in leprosy, due to infiltration by M. leprae or as part of lepra reaction, has been recognized.

The reported prevalence varies from 1% to 70%.8-10 Acute and chronic symmetric polyarthritis involving hand joints, mimicking rheumatoid arthritis (RA), has been described with or without lepra reaction.11 Acute onset painful oedema of hands with marked restriction of movements and nodules along the extensor tendons was described in 1980.10 Pure enthesitis of the heel,12 sacroilitis,13 cryoglobulinemic vasculitis,14 dermatomyositis,10 tenosynovitis and vasculitic rash10 are included in the spectrum of rheumatological manifestations of leprosy. However, almost all of these major reports are in patients with characteristic features of leprosy.

References 1. Britton WJ, Lockwood 2004;363:1209-19.

DN.

Leprosy.

Lancet

2. The World Health Organization – Fact sheet on leprosy. [Accessed June 21, 2006].

3. The World Health Organization – India website information on leprosy. [Accessed June 21, 2006].

4. Making progress towards leprosy Editorial. Lancet 2006;367:276.

elimination.

5. Messner RP. Arthritis due to mycobacteria, fungi and parasites. In: Koopman WJ, McCarty DJ, editors.

Arthritis and allied conditions. 13th ed. Maryland: Williams and Wilkins; 1997: p. 2305-20.

6. Crawford CL, Hardwicke PM. The Charcot foot.

Lancet 2003;361:1225.

7. Gratacos J, Vila J, Brancos MA, Marco MA, Munoz Gomez J. Septic arthritis caused by group G Streptococcus in a female patient with lepromatous leprosy. Med Clin 1991;96:35-6.

8. Bonvoisin B, Martin JM, Bouvier M, Bocquet B, Boulliat J, Duivon JP. Articular manifestations in leprosy. Sem Hop 1983;59:302-5.

9. Atkin SL, el-Ghobarey A, Kamel M, Owen JP, Dick WC. Clinical and laboratory studies of arthritis in leprosy. Br Med J 1989;298:1423-5.

10. Albert DA, Weisman MH, Kaplan R. The rheumatic manifestations of leprosy (Hansen disease). Medicine 1980;59:442-8.

11. Gibson T, Ahsan Q, Hussein. Arthritis of leprosy. Br J Rheumatol 1994;33:963-6.

12. Carpintero-Benitez P, Logrono C, Collantes-Estevez E. Enthesopathy in leprosy. J Rheumatol 1996;23:1020-1.

13. Cossermelli-Messina W, Festa Neto C, Cossermelli W. Articular inflammatory manifestations in patients with different forms of leprosy. J Rheumatol 1998;25:111-9.

14. Thappa DM, Karthikeyan K, Vijaikumar M, Koner BC, Jayanthi S. Leg ulcers in active lepromatous leprosy associated with cryoglobulinaemia. Clin Exp Dermatol 2002;27:451-3.

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Evaluate Balance and Gait with the Get Up and Go Test In this brief and practical test, the older patient is asked to rise from a chair, walk 10 feet, turn around, walk back and then sit–down in the chair. The test is timed and usually takes 15 seconds. The clinician should observe the use of the arms or hands to assist the rise from the chair, the height and length of the steps, use of the arms when walking, balance and ease of the turnaround (the most unstable portion of the gait), and how easily the older patient sits down again.

There are no established norms to score the test, but observation of these aspects of the older patient’s performance during the Get Up and Go test can provide important information on the risk for falls and driving problems.

Source: eMedinewS

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PEDIATRICS

Asperger Syndrome in Adolescence: A Clinical Conundrum Complicated by DSM-5 DE Greydanus

Abstract Asperger syndrome is a term used to provide a description of individuals with a normal or above normal intelligence but with limited social skills and stereotypic mannerisms. Although their language skills are normal, a variety of comorbidities can be seen including attention-deficit hyperactivity disorder, sleep disorders, depression, violent tendencies, anger, anxiety, and/or psychosis. It has been formally excluded from the American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders (DSM-5) as of 2013.This article considers principles of management of youth with Asperger syndrome that includes supportive counseling, psychotherapy, and in some situations, psychopharmacology. Clinicians who care for adolescents can help their adolescent patients achieve useful lives even with a diagnosis of Asperger syndrome. The DSM-5 omission does not mean that this condition has disappeared nor will it cease to be a confusing, clinical conundrum for clinicians caring for youth.

Keywords: Asperger, autism, DSM

A

lthough autism was not formally recognized until the 20th century, examples of probable autism are found earlier. For example, Martin Luther (1483–1546), through his note taker, Mathesius, presents an account about a 12-year-old boy with features of severe autism.1 The first documented individual with autism may be Hugh Blair of Borgue, Scotland, as described in a 1747 court case in which this person’s brother wanted to acquire Hugh’s inheritance.

Another early account of autism may be provided

by Jean Itard, a medical student, who managed what history has labeled as the Wild Boy of Aveyron who was a feral child first found in 1798.

of Affective Contact.2 These children had severe social skills dysfunction including the first reported patienta 5-year-old boy (Donald T) with a described “affective contact” problem and yet had a phenomenal memory for faces and names, including names of community houses. The term, autism, was derived from a Swiss psychiatrist, Eugen Bleuler (1857-1939), who coined the words autism (Latin: autismus for self) as well as schizophrenia.

Current concepts of autism can be traced to Leo Kanner MD (1894-1981) who became the first chair of child psychiatry and is called the father of child psychiatry in the United States. Professor Kanner was at Johns Hopkins University (Baltimore, Maryland) and published a historical, 1943 article based on his evaluation of 11 children, called Autistic Disturbances

In 1944, Austrian pediatrician Hans Asperger (19061980) presented four boys (out of more than 400 children) with features of autism who possessed an unusual ability to recite detailed information.3 Professor Asperger became Chair of Pediatrics at the University of Vienna and concluded: “We are convinced, then, that autistic people have their place in the social community.

They fulfill their role well, perhaps better than anyone else could, and we are talking of people who as children had the greatest difficulties and caused untold worries to their care-givers.”3

*Professor and Founding Chair Dept. of Pediatric and Adolescent Medicine Western Michigan University School of Medicine Kalamazoo, Michigan Address for correspondence Dr Donald E Greydanus Western Michigan University School of Medicine 1000 Oakland Drive, Kalamazoo, Michigan 49008 E-mail: donald.greydanus@med.wmich.edu

His work was published in German and was not translated into English until 9 years after his death in 1980; unfortunately, this resulted in his work being ignored by the English-speaking medical community until the 1990s. The school he started for children with “autistic psychopathy” was destroyed near the end of World War II and much of his early research was lost. However, we have the concepts of his work in this early part of the 21st century, and the term, Asperger syndrome, which represents an individual

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PEDIATRICS with a higher function form of autism. One of Professor Asperger’s patients became a professor of astronomy while another earned a Nobel laureate in literature.

Asperger syndrome as a term was first used in 1981 by Lorna Wing, a British psychiatrist, who was the mother of a daughter with this condition.4 Hans Asperger summarized his research in a paper published in his native language, German, in 1977.5 It is intriguing to note that various scholars have speculated that Hans Asperger himself had features of his identified Asperger syndrome.6 As psychiatric diagnoses were developed, considerable confusion arose regarding how to label and study them. Attempts to formally classically mental illness were improved with the inauguration of the American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders (DSM-I) in 1952 and DSM-II in 1968. The DSM-III expanded the list of mental illness from 106 in DSM-I to 265 and when it was published in 1980, autism was added to this list. Criteria for autistic disorder was based on a classic paper of Sir Michael Rutter (born 1933) who identified four core features: social impairment, insistence on sameness, language dysfunction, and onset prior to 30 months of age.7 The DSM-IV was published in 1994 and listed Asperger syndrome as one of five aspects of autistic spectrum disorder that also included autistic disorder, Rett syndrome, childhood disintegrative disorder, and pervasive developmental disorder-not other specified.8,9 One of the changes found in DSM-5 that was published in 2013 was to remove the term Asperger syndrome from the definition of autism spectrum disorder.10 Asperger Syndrome in the 21st Century Despite the controversy over the categories of autism, there remain a number of children and adults who have features of what for decades has been called Asperger syndrome. Individuals with this diagnosis have been written about in contemporary fiction works as well as assigned to various known human beings.11 Part of the controversy around this syndrome is the failure to understand its prevalence as well as its etiology.

Etiologic concepts have typically centered on what have been called “deficits in the theory of mind” that results in social cognition dysfunction; however, such ideals remain controversial and unproven.12 Nevertheless, Asperger syndrome refers to individuals with abnormal behaviors (i.e., stereotyped and obsessional) along with identified or observed dysfunction in communicative and social-emotional

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Table 1. Proposed CNS Changes in Asperger Syndrome13,14 ÂÂ

Dysfunction of neural and lipid membrane integrity and amygdala-hippocampal complex maturation

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Disorder of right hemisphere white matter

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Changes in excitability

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Reduced CNS gray matter

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Dysfunction of Broca’s language neural network dynamics

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Amygdala and hippocampal dysfunction

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Caudate and anterior cingulate cortex dysfunction

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Frontostriatal pathway dysfunction

modulation

of

corticospinal

behavior.9 Although all studies are not in agreement, research has suggested various central nervous system abnormalities in those with Asperger syndrome as outlined in Table 1.13,14 Research often points out abnormalities in the amygdala–hippocampus area and the right hemisphere.

Adolescents with Asperger Syndrome Adolescents with Asperger syndrome are typically viewed by clinicians as having a neurodevelopmental disorder within autistic spectrum disorder in which they have problems communicating with others and understanding the feelings and emotions of others.9 They have problems following conversations especially with several individuals involved in simultaneous talking; such difficulty reflects audiovisual speech perception dysfunction. These features are seen despite the relatively normal or even high verbal intelligence that is found and as identified by the work of Hans Asperger and others.15 There are numerous case reports from around the world (children, adolescents, and adults), labeled as having Asperger syndrome, who have unusual abilities of memory or other cognitive accomplishments.15

Comorbid Conditions in Adolescent Asperger Syndrome The profile of youth with Asperger syndrome includes those with social skills dysfunction who have a wide mixture of neurological as well as psychiatric symptomatology (including depression and anxiety) in addition to abnormal movements (Table 2).16 Movement dysfunction includes stereotyped behaviors, various ritualistic or compulsive behavior, hand flapping, and

PEDIATRICS toe walking.16 Each individual is unique and this is compounded by considerable confusion as well as inconsistency in research and in clinical medicine in terms of Asperger syndrome diagnosis.17 Thus, features that are part of or are comorbidities of Asperger syndrome can be debated by various researchers and clinicians. However, many of these persons given the label of Asperger syndrome may display violent behavior, sleep disorders (i.e., insomnia), anxiety, depression, ADHD, and/or features of psychosis.18,19 Disorders of depression and anxiety are the most common comorbid psychiatric conditions found in these persons.19 Adolescents with Asperger Syndrome: Concepts of Management As noted, each person with a diagnosis or suspicion of having Asperger syndrome is a unique individual requiring a personalized approach to allow maximal development of his or her potential. Every human being has a right to maximum help as well as happiness and clinicians who deal with adolescents can be very instrumental in this regard. Research reveals that persons with Asperger syndrome may have negative health and social profiles.20 Thus, a comprehensive evaluation of medical and psychological health is necessary for these and all patients seen by clinicians who should serve as medical advisors to their patients.

Although typically diagnosed in males, one must be aware that females can fit a profile matching that of one with Asperger syndrome.21 The clinician should ask about any past or current experience with bullying in this patient since some members of society in all countries will prey on those perceived as being different, weak, or vulnerable.22 It is important for clinicians wishing to help their patients learn to understand as much as possible the

Table 2. Comorbidities of Asperger Syndrome16-19 ÂÂ

Anger

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Anxiety

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Attention-deficit hyperactivity disorder

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Depression

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Psychosis

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Ritualistic mannerisms

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Sleep dysfunction (i.e., insomnia)

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Violent behavior

feelings of their patients. The development of empathy or the ability to share other’s feelings can be difficult for those with Asperger syndrome and can also be seen in some clinicians who are not trained in developing an empathic brain.

Research on those with Asperger syndrome demonstrates that these persons have considerable dysfunction in self-awareness and self-reflection that can complicate their efforts at self-understanding and selfadvocacy movements.23 If possible, it can be beneficial to reach out to parents who have adolescents with Asperger syndrome to provide them with suggestions for help since they may have intense fears for their offspring surviving and thriving in an often unempathic world.24 Psychotherapy can be of considerable help to individuals with Asperger syndrome struggling with issues noted in Table 2.

Anger and Asperger Syndrome Some adolescents with Asperger syndrome may have intense anger that typically presents with tantrums, agitation, and overt aggression as well as violence toward others that may bring them to medical, legal, and/or psychological attention.25 The forensic literature does contain case reports in which persons have been murdered by individuals with Asperger syndrome and some scholars have argued that those with Asperger syndrome may not be criminally responsible for their crimes even if not identified with a psychotic disorder.26 Others in the field of jurisprudence have concluded that this diagnosis neither excuses nor justifies one with Asperger syndrome committing various offenses including arson, stalking, other harassing, sexual violence, or other acts of physical violence.27 Scholars who have reviewed 177 of former Asperger patients of Hans Asperger have concluded that there was no increase in criminal convictions in this inaugural cohort of patients.27 Pharmacologic Management There is no specific role for psychopharmacologic management for Asperger syndrome in adolescents unless there is a specific comorbid condition that may be treated with drugs, such as ADHD, depression, anxiety, psychosis, or others. For example, since ADHD and nicotine dependence are increased in those with Asperger syndrome, pharmacologic management of these specific coexisting disorders may be beneficial to this specific patient with Asperger syndrome.28 Those with Asperger syndrome and obsessive compulsive

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PEDIATRICS symptoms may note improvement with antipsychotic medication, such as aripiprazole.29 Those with clinical depression can be diagnosed with clinical interview and screening testing (i.e., Beck Depression Inventory) while management options include psychotherapy with or without pharmacologic intervention.30 A minority of young adults with Asperger syndrome may have comorbid psychosis, and thus, expert application of antipsychotic medication becomes a paramount part of the therapy.31 A recent report notes that traditional Japanese herbal medication, yokukansan (TJ-54), was noted to be beneficial in patients with Asperger syndrome who noted improvement in lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, severe irritability, and even inappropriate speech.

Certainly, more research is needed to verify such research results from this group in Izumo, Japan, that looked at children, adolescents, and adults.32 Summary Asperger syndrome is a term used to provide a description of individuals with a normal or above intelligence but with limited social skills and stereotypic mannerisms. Biological abnormalities are listed in Table 1. Although their language skills are normal, a variety of comorbidities are seen as noted in Table 2. This manuscript considers principles of management of youth with Asperger syndrome that includes supportive counseling, psychotherapy, and, in some situations, psychopharmacology. Clinicians who care for adolescents can help their adolescent patients achieve useful lives even with a diagnosis of Asperger syndrome. The removal of this term from the DSM-5 does not mean these patients do not exist nor does it mean they do not need help from empathetic clinicians who care for adolescents.

References 1. Greydanus DE, Toledo-Pereyra LH. Historical perspectives on autism: its past record of discovery and its present state of solipsism, skepticism, and sorrowful suspicion. Pediatr Clin N Am 2012;59:1-11.

2. Kanner L. Autistic disturbances of affective contact. Nerv Child 1943;2:217-50.

3. Asperger H. Die autistischen psychopathen im Kindesalter.

Arch Psychiatr Nervenkr 1944;117:76-136.

6. Lyons V, Fitzgerald M. Did Hans Asperger (1906-1980) have Asperger Syndrome? J Autism Dev Disord 2007;37:2020-1.

7. Rutter M. Diagnosis and definition of childhood autism.

J Autism Dev Disord 1978;8(2):139-61.

8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, IV edition (DSM-IV).

Washington, DC, 1994.

9.

Nazeer A. Autistic spectrum disorders. In: Neurodevelopmental Disabilities: Clinical Care for Children and Young Adults. Patel DR, Greydanus DE, Omar HA, Merrick J (editors). Dordrecht, Germany: Springer 2011;97-110.

10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5).

Washington, DC, 2013.

11. Pourre F, Aubert E, Andanson J, Raynaud JP. Asperger syndrome in contemporary fictions.

Encephale 2012;38(6):460-6.

12. Samson AC, Huber O, Gross JJ. Emotion regulation in Asperger’s syndrome and high-functioning autism. Emotion 2012;12(4):659-65.

13. Yu KK, Cheung C, Chua SE, McAlonan GM. Can Asperger’s syndrome be distinguished from autism? An anatomic likelihood meta-analysis of MRI studies. J Psychiatry Neurosci 2011;36(6):412-21.

14. Semrud-Clikeman F, Fine JG, Bledsoe J, Zhu DC. Magnetic resonance imaging volumetric findings in children with Asperger syndrome, nonverbal learning disability, or healthy controls. J Clin Exp Neuropsychol 2013;35(5):540-50.

15. Frith U. Emanual Miller lecture: confusions and controversies about Asperger syndrome. J Child Psychol Psychiatry 2004;45(4):672-86.

16. Rinehart NJ, Bradshaw JL, Brereton AV, Tonge BJ. A clinical and neurobehavioural review of high-functioning autism and Asperger’s disorder. Aust NZJ Psychiatry 2002;36(6):762-70.

17. Sharma S, Woolfson LM, Hunter SC. Confusion and inconsistency in diagnosis of Asperger syndrome: a review of studies from 1981 to 2010. Autism 2012;16(5):465-86.

18. Mazzone L, Ruta L, Reale L. Psychiatric comorbidities in Asperger syndrome and high functioning autism: diagnostic challenges. Ann Gen Psychiatry 2012;11(1):16-20.

19. Gillberg C, Billstedt E. Autism and Asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand 2000;102(5):321-30.

20. Balfe M, Tantam D. A descriptive social and health profile of a community of adults and adolescents with Asperger syndrome. BMC Res Notes 2010;3:300-10.

21. Waris P, Kulomäki T, Tani P. Asperger’s syndrome in females.

Duodecim 2011;127:1571-7.

4. Wing L. Asperger’s syndrome: a clinical account. Psychol Med 1981;11:115-29.

22. Sofronoff K, Dark E, Stone V. Social vulnerability and bullying in children with Asperger syndrome. Autism 2011;15(3):355-72.

5. Asperger H. The lived life. 50 years of Pediatrics (In German).

Pediatr Padol 1977;12:214-33.

23. Jackson P, Skirrow P, Hare DJ. Asperger through the looking glass: an exploratory study of self-understanding

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PEDIATRICS in people with Asperger’s syndrome. J Autism Dev Disord 2012;42(5):697-706.

DR, Omar HA, Feucht C, Merrick J (editors). Berlin/Boston: De Gruyter 2012;157-99.

24. Griffith GM, Totsika V, Nash S, Jones RS, Hastings RP. We are all silently coping. The hidden experiences of parents of adults with Asperger syndrome. J Intellect Dev Disabil 2012;37(3):237-47.

29. Celik G, Tahiroglu AY, Firat S, Avci A. Aripiprazole improved obsessive compulsive symptoms in Asperger’s disorder.

Clin Psychopharmacol Neurosci 2011;9(3):134-6.

25. Quek LH, Sofronoff K, Sheffield J, White A, Kelly A. Cooccurring anger in young people with Asperger’s syndrome.

J Clin Psychol 2012;68(10):1142-8.

26. Katz N, Zemishiany Z. Criminal responsibility in Asperger’s syndrome. Isr J Psychiatry Relat Sci 2006;43(3):166-73.

27. Hippler K, Viding E, Klicpera C, Happé F. No increase in criminal convictions in Hans Asperger’s original cohort. J Autism Dev Disord 2010;40(6):774-80.

28. Greydanus DE, Feucht C, Hawver EK. Substance abuse disorders In: Adolescent Medicine: Pharmacotherapeutics in General, Mental, and Sexual Health. Greydanus DE, Patel

30. Greydanus DE, Patel DR, Feucht C (editors). Pediatric psychopharmacology in the 21st century. Pediatr Clin N Am 2011;58(1):1-314.

31. Nazeer A, Calles JL. Schizophrenia. In: Adolescent Medicine: Pharmacotherapeutics in General, Mental, and Sexual Health. Greydanus DE, Patel DR, Omar HA, Feucht C, Merrick J (editors). Berlin/Boston: De Gruyter, 2012;269-81.

32. Miyaoka T, Wake R, Furuya M, Liaury K, Leda M, Kawakami K, et al. Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 12 week prospective, open-label study. BMC Psychiatry 2012;12:215-9.

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Global News Updates ÂÂ

Using ultrasound as the first diagnostic imaging technique to detect appendicitis in children produces comparable outcomes to computed tomography (CT) scanning with less radiation and without increasing hospital length of stay, according to a retrospective study published in the December issue of the American Journal of Roentgenology.

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Advocates for newborn health are proposing to accelerate kangaroo mother care (KMC) as the standard of care for preterm infants.”A multi–stakeholder group is now in the process of developing both global– and national–level strategies and implementation plans around the several parallel streams of work needed to ‘bend the curve’ as part of the Every Newborn Action Plan to be launched in May 2014,” said Dr. Cyril Engmann from the Bill & Melinda Gates Foundation, Seattle, Washington. KMC comprises a host of care practices for preterm infants which include continuous skin–to–skin contact, breastfeeding, and close follow– up after discharge from a health facility.

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In a retrospective study reported online in the Journal of Pediatrics, among young hospital patients, factors like older age and the presence of multiple medical conditions were associated with higher rates of hospital– associated venous thromboembolism (VTE). Compared with children ages 2 to 9, the rate of hospital– associated VTE was about four times higher for teens ages 14 to 17 and nearly eight times higher for young adults ages 18 to 21.

ÂÂ

The US FDA has given approval for studies to begin on a medicinal form of marijuana for the treatment of intractable epilepsy in children. The drug, cannabidiol (Epidiolex, GW Pharmaceuticals) is the largest nonpsychoactive component of the cannabis plant. The product has also been granted orphan drug status for the treatment of children with Dravet syndrome, a rare and severe syndrome of infantile–onset, genetic, drug–resistant epilepsy.

Source: eMedinewS

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Pharmacology

A Comparative Analysis of Commercial Metformin Tablets P Elango*, Ramesh†, S Shanmuganathan‡

Abstract Objective: Five commercial brands were analyzed with respect to their physical characters, chemical content, and drug release.

Methods: The brands of metformin were randomly selected. All the groups were coded and analyzed. The tablets were examined for their shape, size, weight, and color and the tablets were tested for their friability, disintegration, drug content, and purity using standard procedures. Results and discussion: On physical inspection, Brand C 500 was is the smallest and Brand D 500 SR was the largest in size. Brand C 500 was lesser in weight while Brand E XR 500 weighed more. On purity test, all other brands passed the standard for purity. All the brands had loss in weight less than 1% after the friability test. On chemical content examination, variation was seen between the batches as well as the brands. The brands such as Brand A XL 500 and Brand D 500 SR contained the required content. But the brands like Brand C 500 and Brand E XR 500 had only lesser content and failed in the validity test. Conclusion: The physical properties of the five brands of metformin tablets were analyzed. Sustained release dosage form was mainly designed for maintaining therapeutic blood or tissue levels of the drug for extended period of time.

Apart from the color and shape, the weight and size are very important to improve patients’ compliance. It is the duty of the pharmaceutical company to manufacture proper dosage forms to achieve the therapeutic goal.

Keywords: Metformin, physical aspects, sustained release, content, disintegration time

M

etformin hydrochloride (MET) is chemically N,N-dimethylimidodicarbonimidic diamide hydrochloride (1, 1-dimethylbiguanide hydrochloride) that acts by decreasing intestinal absorption of glucose, reducing hepatic glucose production and increasing insulin sensitivity (Fig. 1) Metformin is considered as the first-line oral hypoglycemic agent in the treatment of type 2 diabetes mellitus. MET is the drug of choice in obese patients.1–3 Metformin activates adenosine monophosphateactivated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance and metabolism of glucose and

*Associate Professor Dept. of Pharmacology Sri Ramachandra Medical College and Research Institute, Porur, Chennai †Lecturer ‡Professor Dept. of Pharmaceutics Sri Ramachandra College of Pharmacy, Sri Ramachandra University, Porur, Chennai Address for correspondence Dr P Elango Dept. of Pharmacology Sri Ramachandra Medical College and Research Institute Sri Ramachandra University Porur, Chennai - 600 116 E-mail: drpelango@yahoo.com

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

H 3C H3C

N

C NH

NH

C

NH2

HCI

NH

Figure 1. Chemical structure of MET.

fats. Activation of AMPK is required for metformin’s inhibitory effect on the production of glucose by liver cells. It is an official drug in Indian Pharmacopoeia,4 British Pharmacopoeia,5 European Pharmacopoeia,6 and United States Pharmacopoeia BP.7 Many brands are available for metformin generic in the market. This study was committed to evaluate the quality of the five brands of metformin. The brands having high quality should be equivalent not only in their basic chemical structure and dosage forms but also in their content, purity, friability and dissolution rates.8 Objective The study was a single-blind comparative analysis of five brands of metformin tablets and this study intended: ÂÂ

To evaluate the physical quality in their appearance, purity in their substance, friability on handling, and the content in their preparations.

Pharmacology ÂÂ

To evaluate the time taken for their dissolution/ release.

spectrophotometer method at specific absorbance (232 nm) as per Indian Pharmacopoeia.8

ÂÂ

To analyze the observations and make a comparison of the brands.

Friability Test

Methodology Five commercial brands of metformin were randomly selected. Metformin brands having label strength of 500 mg were purchased from a retail pharmacy in Chennai.

Three batches were taken from each brand. All tests were performed within product expiration dates.

The brands were coded (Table 1) and analyzed in the following procedures. The analysts were kept blinded.

It is the tendency of the tablets to powder, chip, or fragment and this can affect the elegance appearance and consumer acceptance of the tablet, and can also add to the tablet’s weight variation or content uniformity problems. Friability is a property that is related to the hardness of the tablet. An instrument called friabilator is used to evaluate the ability of the tablet to withstand rattling in packaging, handling, and shipping.

Procedure

The tablets were visually examined for their shape, size, weight and color; the tablets were tested for their purity, friability, and content, and dissolution rates were estimated using standard procedures.

Twenty tablets were weighed and subjected to abrasion using a tablet friability tester (Veego Instruments Corporation, Mumbai, India) at 25 revolutions per minute (rpm).

Physical Inspection

ÂÂ

Weigh 20 tablets altogether = W1

The shape and color of the different brands of tablets were examined visually. The size was examined with the help of Vernier caliper. Tablets of each brand were weighed individually using a digital analytical balance (Ohaus Adventure, China).

ÂÂ

Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e., 25 rpm for 4 min)

ÂÂ

Weigh 20 tablets (after friability) = W2

ÂÂ

Friability (% loss) = W1 − W2 % W1 × 100

Chemical Content Determination

Purity Assay to estimate the purity of metformin of the given five brands was carried out using ultraviolet (UV)

Table 1. Coding of Tablets Brand BRAND - A XL 500

Coding

Expiry date

No of tablets

GF01

FEB 2014

25

GF02

APR 2014

25

GF03

APR 2014

25

XM01

FEB 2014

25

XM02

JAN 2014

25

BRAND - B 500

XM03

NOV 2014

25

BRAND - C 500

GP01

May 2015

25

GP02

Jan 2015

25

GP03

Apr 2015

25

GM01

Mar 2014

25

GM02

Mar 2014

25

GM03

May 2014

25

CP01

July 2014

25

CP02

Aug 2014

25

CP03

Mar 2012

25

BRAND - B SR 500

BRAND - D SR

BRAND - E XR 500

This is used to determine whether the individual content of the tablets are within the limits set with reference to the average content of the sample.

Metformin powder is weighed in amounts of 0.1, 0.2, 0.3, 0.4, 0.5, and 0.75 mg. Each sample was dissolved separately in 1 mL of 0.2 M HCl and shaken up for 5 min. Five milliliters of 10−5 M KMnO4 was then added, warmed in a water bath at 50°C for 10 min, and cooled for 3 min before 2 mL of 10−4 M methylene blue and 100 mL of distilled water was added. Five milliliters aliquot of the final volume was taken for each weight. The absorbance of the resulting solutions was determined at 663 nm. The procedure was applied to the five brands of metformin employed in the study.

Dissolution Rate Determination In vitro dissolution rate is an important tool to predict the in vivo bioavailability and bioequivalence and to decide on interchangeability.9 As per Food and Drug Administration guidance for highly soluble drugs, a single-point dissolution test specification of 85% in 60 min or less is sufficient as a quality control test for uniformity between different batches.10 Similarly, as per the European Medicines Agency (EMA) guidance, when more than 85% of the active substances are dissolved

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

779

Pharmacology within 15 min, it is sufficient as a quality control test for uniformity between different batches.11,12 For this reason, dissolution testing of solid oral drug products has emerged as one of the most important control tests for assuring product uniformity and batch-to-batch equivalence.13 Therefore, any dosage forms having good dissolution rate is considered to be having good quality and is an important part of good manufacturing practice.14 Before performing dissolution test, six serially diluted solutions of pure metformin with the concentration of 0.3125 to 10 µg/mL were prepared from a stock solution and a standard curve was drawn. The curve was linear between 0.3125 and 10 µg/mL. The dissolution test was undertaken using USP apparatus II (Erweka DT6R, Gemini BV, The Netherlands) with the rate of 100 rpm at 37°C on six tablets of each brand. The dissolution medium was 900 mL phosphate buffer (pH = 6.8). To draw dissolution profile, 5 mL of dissolution samples were withdrawn at different time intervals up to 60 min and replaced with the same volume of prewarmed dissolution medium.

Subsequently, samples after 100-fold dilution were assayed by UV spectrophotometer at an absorbance wavelength of 232 nm. The concentration of each sample was determined from a calibration curve (Fig. 2).

Medium: pH 6.8 phosphate buffer prepared by dissolving 6.8 g of monobasic potassium phosphate in 1,000 mL of water and adjusting with 0.2 N sodium hydroxide to a pH of 6.8 in 0.1; 1,000 mL. Apparatus II: 100 rpm, for tablets labeled to contain 500 mg.

Time: 1, 3, and 10 hours.

Procedure: Determine the amount of MET (C4H11N5·HCl) dissolved by UV absorption at the wavelength of maximum absorbance at about 232 nm on portions of the solution under test passed through a 0.45-m hydrophilic polyethylene filter and suitably diluted with Medium. Calculate the amount of MET, in percentage, released at each time point by the formula as follows: C × (Au / As) × (V - Vs) + (C60 × Vs) + (C180 × Vs)] × 100

L where C is the concentration of the standard solution in mg/mL; Au and As are the absorbances of the solution under test and the standard solution, respectively; V is the initial volume of medium in the vessel, in mL; Vs is the volume withdrawn from the vessel for previous samplings, in mL; C60 is the concentration of MET in the medium determined at 1 h, in mg/mL; C180 is the concentration of MET in the medium determined at 3 h,

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Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

1.2 A B 1 S 0.8 O R 0.6 B 0.4 A N 0.2 C 0 E -0.2

Series 1

Linear (Series 1)

y = 0.0193 x -0.0128 R2 = 0.9967

0

10

20

30

40

50

60

CONCENTRATION

Figure 2. Calibration curve.

in mg/mL; 100 is the conversion to percentage; and L is the tablet label claim in mg.

RESULTS AND DISCUSSION Physical Inspection The different brands of metformin tablets were examined in their physical aspects, namely, shape, size, weight, and color, and the details are given in table 2.

Size of the Tablets The size of the tablets is above 0.50 cm in all the brands except Brand C 500 having only the size around 0.323 ± 0.003 cm, being the smallest. The size of the Brand D 500 SR is 0.71 cm, being the largest of the brands examined.

There is no significant difference between batches of the brands. The size of dosage forms determines the compliance of the patients.

Weight of the Tablets The weight of the tablets are in the range of 0.75-0.85 g except the Brand C 500 having only 0.55 g and being lesser in weight, while the Brand E XR 500 weighs more (0.85 g) among the brands examined. There is no significant difference between batches of the brands.

Purity A tablet will usually contain active ingredient and vehicle matter. This study is conducted to identify the actual percentage of concentration of active ingredient of a single tablet of these five brands.

The purity assay showed that the five different brands contained different concentrations of the pure chemical and are found to be chemically not equivalent (Table 2).

One of the batches of Brand B SR 500 (XM01), another one of Brand C 500 (GP01), and one more of Brand E XR 500 (CP02) contained only 85%, 86%, and 85% of the ingredient, respectively, and these batches failed

Pharmacology Table 2. Physical Aspects Brand

Coding

Shape

Size Avg (cm)

Weight

Color

Friability %

Drug Purity content (%w/w) (mg)

Purity result

Brand A XL 500

GF01

Capsule shape with convex face

0.62

0.75

White

0.133

550

110

PASS

GF02

Capsule shape with convex face

0.61

0.75

White

0.133

540

108

PASS

GF03

Capsule shape with convex face

0.615

0.756

White

0.133

501

100

PASS

XM01

Capsule shape with flat face and bevel edges

0.50

0.75

White

0.133

425

85

FAIL

XM02

Capsule shape with flat face and bevel edges

0.506

0.75

White

0.136

550

110

PASS

Brand B 500

XM03

Capsule shape with convex face

0.52

0.75

White

0.268

474

95

PASS

Brand C 500

GP01

Capsule shape with concave face and bevel edges

0.32

0.55

White

0.225

431

86

FAIL

GP02

Capsule shape with concave face and bevel edges

0.323

0.55

White

0.256

511

102

PASS

GP03

Capsule shape with concave face and bevel edges

0.326

0.55

White

0.133

469

94

PASS

GM01

Oval shape

0.64

0.71

White

0

512

102

PASS

GM02

Oval shape

0.653

0.70

White

0

519

104

PASS

GM03

Oval shape

0.653

0.70

White

0

484

97

PASS

CP01

Capsule shape with convex face

0.536

0.85

White

0.618

550

110

PASS

CP02

Capsule shape with convex face

0.53

0.85

White

0.458

426

85

FAIL

CP03

Capsule shape with convex face

0.533

0.85

White

0.133

462

92

PASS

Brand B SR 500

Brand D 500 SR

Brand E XR 500

the validity test of 90% concentration. All other brands passed the validity test.

Friability Test The difference in weight loss before and after the friability test is analyzed. If it is to be declared as stable preparation for handling and transport, it must be less than or equal to 1%. The friability is expressed as the loss of mass and it is calculated as a percentage of loss of weight in the initial weight.15 All the brands are having the weight loss less than 1% after the friability test. But among the batches of the brands examined, Brand A

XL 500 have no significant difference within their three batches. The batch of Brand B SR 500 coded as XM03 has higher friability. It is because of being conventional or short-acting dosage form. The brand, Brand D 500 SR, has no weight loss in friability test and it is a very stable dosage form of the brands examined. The batches of Brand E XR 500 coded as CP01 and CP02 have got higher friability than code CP03.

Chemical Content We examined only the tablets having concentration of 500 mg of metformin. A wide range of variations is

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

781

Pharmacology

Batch 01

Batch 02

Series 2

Series 3

Series 4

Invitro Drug Release for GP 01,02,03 120 % Drug Release

seen in the contents of the tablets. The variation is seen between the batches as well as the brands. A brand should contain 90% of the substance (450â&#x20AC;&#x201C;550 mg) to clear the validity test. The brands such as Brand A XL 500 and Brand D 500 SR contain the required content.

But the brands like Brand C 500 and Brand E XR 500 had only lesser content and failed the validity test.

The content is also not uniform among batches (Fig. 3).

100 80 60 40 20 0

Batch 03

0

600

15

30

45

60

Time in Min

500

Figure 6. Release of Brand C.

400 300 200

Series 1

100 Brand B Brand C Brand D Brand E SR 500 500 500 SR XR 500

Figure 3. Drug content in milligrams per tablet.

Series 1

Series 3

Invitro Drug Release for GF 01,02,03

120 % Drug Release

Series 2

120 % Drug Release

Brand A XL 500

100 80 60 40 20 0

100 80

0

200

400 Time in Min

600

800

Figure 7. Release of Brand E.

60 40 20 0

Dissolution Rate 0

200

400 Time in Min

600

800

Figure 4. Release of Brand A.

Series 1

Series 2

Series 3

120 100 80 60 40

Brand C 500 had taken only 60 min for 94%-97% release as a short-acting form (Fig. 6).

20 0

Dissolution or release of the contents is more than 10 h in all brands of sustained dosage forms. But the release in case of Brand B 500, batch XM03, and all the batches of Brand C 500 is in 60 min because of their conventional or short-acting dosage forms. Brand A XL 500 released more than 90% of their contents in 10 h and it is sustained release dosage form as shown in (Fig. 4).

Two batches (XM01, XM02) of Brand B SR 500 took 10 h to release 83%-100% of its contents, but one batch (XM03) being short acting had taken 60 min to release more than 90%. This shows that the long-acting forms are suitable for less frequency in administration of drugs and improves patientsâ&#x20AC;&#x2122; compliance (Fig. 5).

In vitro Drug Release for XM 01,02,03 % Drug Release

Series 3

In vitro Drug Release for CP 01,02,03

0

0

200

400

600

800

Time in Min

Figure 5. Release of Brand B.

782

Series 2

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

Brand D 500 SR being sustained release form released 86%-92% 10 h (Fig. 7). Brand E XR 500 had release time of 10 h for 80%-99% of their contents (Fig. 8).

Pharmacology Main Limitations of the Study Dissolution test in vitro will preconceive the in vivo behavior of a drug. But the real bioavailability and bioequivalence of the products can be concluded only in vivo studies. The human gastrointestinal tract with its own nature and various other factors affect its activity, the generalization of dissolution conditions, and thus results of this study is not aptly applied. In vivo and in vitro comparison studies are required to confirm findings in this study.9 Conclusion The physical properties of five brands of metformin tablets were analyzed and results were presented.

Sustained release dosage form is mainly designed for maintaining therapeutic blood or tissue levels of the drug for extended period of time with minimized local or systemic adverse effects. Economy and greater patient compliance are other advantages of sustained release preparations. Apart from the color and shape, the weight and size are very important to improve patients’ compliance. It is the duty of the pharmaceutical company to manufacture the dosage forms sustaining more rattling in handling, to have more shelf life, and to supply the drugs in pure form with recommended content. This only will achieve the therapeutic goal.

References 1. Clinical Guidelines Task Force, International Diabetes Federation. Glucose control: oral therapy. In: Global Guideline for Type 2 Diabetes. Brussels: International Diabetes Federation 2005:35-8.

2. National Collaborating Centre for Chronic Conditions.

Type 2 diabetes: National Clinical Guideline for Management in Primary and Secondary Care (update).

London: Royal College of Physicians 2008:86.

3. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care 2009;32(Suppl 1):S13-61.

4. Indian Pharmacopoeia, Government of India, Ghaziabad.

The Indian Pharmacopoeia Commission 2007;2:1358.

5. British Pharmacopoeia, Her Majesty’s Stationary Office.

London, UK 2009;1 and 2:3813.

6. European Pharmacopoeia. Council of Europe, France.

3rd edition. 1997;55 and United States Pharmacopoeia BP (The United States Pharmacopoeia).

7. The United States Pharmacopoeia. US Pharmacopoeial Convention, Inc.: Rockville, MD. 31st Revision. 2008;2640.

8. United States Pharmacopoeia and National Formulary USP 24–NF 19; The United States Pharmacopoeial Convention, Inc.: Rockville, MD, 2000;1882-3.

9. Al Ameri MN, et al. The differences between the branded and generic medicines using solid dosage forms: in-vitro dissolution testing. Results Pharma Sci 2012;2:1-8.

10. Food and Drug Administration (FDA). Guidance for industry: dissolution testing of immediate release solid oral dosage forms, August 1997, May 5, 2011.

11. European Medicines Agency (EMA). Note for guidance on the investigation of bioavailability and bioequivalence, July 16, 2001, January 26, 2010.

12. Voegele D. Drug release in vitro: an aid in clinical trials?

Met Find Exp Clin Pharmacol 1992;21(1):55-62.

13. Moore, JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol 1996;20:64-74.

14. Quo Jh, et al. Validation of tablet dissolution method by high-performance liquid chromatography. Drug Develop Industr Pharmacy 2000;26(3):337-42.

15. European Pharmacopoeia 5.0, p. 234.

■■■■

Gaining Weight Losing Strength Versus Losing Weight Gaining Strength When we gain weight, we must acquire more strength and when we lose weight, we must lose the strength. This is a fundamental principle.

If we gain weight and feel weak, it is a disease and when we lose weight and gain strength, we are recovering from the disease. One is not supposed to gain more than 5kg of weight after the age of 20 years. Any weight gain after that will only be due to accumulation of fat, which leads to insulin resistance.

Insulin resistance does not allow food to convert into energy. In the state of insulin resistance, whatever you eat is converted into fat. As it is not converted into energy so you feel weak. When you reduce insulin resistance by drugs or walking, the metabolism becomes normal and whatever you eat gets converted into energy and you start gaining strength.

Source: eMedinewS Dec 28, 2013

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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Around the Globe

News and Views ÂÂ Patients taking prescription antireflux medications

had significantly higher odds of a vitamin B12 deficiency. In a study in JAMA, among patients diagnosed with a vitamin B12 deficiency, a 2 or more years prescription for proton pump inhibitors or histamine 2 receptor antagonists was significantly associated with risk for the deficiency. Patients who received more than 1.5 pills daily of PPIs had significantly greater vitamin B12 deficiency than those who received doses less than 0.75 pills per day.

ÂÂ A new research presented at the American Society

of Hematology annual meeting reports that a next generation genetic therapy appeared to restore the immune system of patients with “bubble boy disease,” but without leading to leukemia as a side effect. Among nine children, ages 3.9 to 10.5 months, diagnosed with X-linked severe combined immunodeficiency (SCID) who received a selfinactivating (SIN) gamma retroviral vector, seven were “alive and well” at 3 years’ post-treatment.

The current standard treatment for X–SCID is hematopoietic stem cell transplantation, but finding a suitable donor is difficult.

ÂÂ The type 2 diabetes drug canagliflozin was

associated with modest weight loss in an early trial of heavy patients who didn’t have hyperglycemia.

In a phase IIb trial reported online in the journal Obesity, obese and overweight patients who didn’t have diabetes lost a significantly larger proportion of body weight on any of three doses of the drug compared with placebo.

ÂÂ Vedolizumab was recommended by wide margins

for the treatment of adults with ulcerative colitis (UC) and Crohn’s disease (CD) at a joint meeting of the US FDA’s Gastrointestinal Drugs Advisory Committee (GIDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRMAC), held on December 9.

ÂÂ The

Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America, and the Pediatric Infectious Diseases Society recommend that all healthcare employers (HCEs) require universal immunizations recommended by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), according to a policy statement. Included with the mandated

784

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

immunizations are those against measles, mumps and hepatitis B. The policy statement recommends that HCEs should consider, on a case-by-case basis, the need for administrative and/or infection control measures to reduce risk for disease transmission among HCP who cannot be vaccinated because of medical contraindications or vaccine supply shortages. HCPs include all paid and volunteer persons working in the healthcare setting who have the potential for exposure to patients and/or to infectious materials. ÂÂ A double-blind, placebo-controlled imaging study

of 17 children and adolescents with autism spectrum disorder (ASD) suggests that a single dose of the hormone oxytocin administered via nasal spray enhances brain activity in key regions, temporarily improving social information processing in children with autism spectrum disorder (ASD).

The findings were published online December 2 in the Proceedings of the National Academy of Sciences.

ÂÂ Exercise can help overweight kids slim down, but

a new study suggests they might be at risk for leg, ankle and foot injuries in the process, according to results published online November 22 in the British Journal of Sports. That could be because their legs are supporting extra weight. Children with a healthy BMI had 4.4 injuries for every 1,000 “athletic exposures” (i.e., 1.5 hours of physical education class or one afterschool sports practice), compared to 5.3 injuries for every 1,000 exposures among kids with an overweight or obese BMI.

ÂÂ Individuals

with sleep apnea and resistant hypertension treated with continuous positive airway pressure (CPAP) over the course of 12 weeks had significant improvements in their 24-hour mean and diastolic blood pressures, but no change in their systolic blood pressure, according to the results of the HIPARCO trial in the December 11, 2013 issue of the Journal of the American Medical Association. CPAP therapy also improved nocturnal BP pattern, with more patients treated with CPAP displaying the nocturnal dipper pattern versus individuals who did not receive CPAP.

ÂÂ Most experts at the World Diabetes Congress

2013 were of the opinion that patients with type 2 diabetes who are at high risk for or who already

Around the Globe have heart failure should not be precluded from receiving dipeptidyl peptidase-4 (DPP–4) inhibitor glucose–lowering agents. They should instead be supervised closely for the first 6 months of therapy, because new findings from the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus - TIMI 53 (SAVOR– TIMI 53) trial indicate that heart–failure cases associated with the use of saxagliptin (DPP–4 inhibitor) appeared to occur primarily in the first 6 months of use of the drug. ÂÂ Indian

origin gynecologist suspended for misconduct in UK: An Indian origin gynecologist, accused of groping a patient’s breasts three years ago, has been found guilty of misconduct by a British panel and suspended from practicing medicine for a year. Angamathu Arunkalaivanan was also found guilty of failing to offer a chaperone or make a record of the breast check in the patient’s notes. “The panel accepted that this is an isolated case and that the breast examination was clinically indicated. However, the manner in which you conducted the breast examination on Patient A was clearly sexually motivated,” Sandra Sturdy, chair of the Medical Practitioners Tribunal Service panel in Manchester, said this week.

“Your conduct in undertaking a breast examination… was a serious breach of trust between patient and doctor and amounted to serious misconduct… The panel has found that your actions have brought the medical profession into disrepute, and that you have breached fundamental tenets of the profession.” Sturdy said the panel had determined that “the need to uphold proper professional standards and public confidence in the profession would be undermined if a finding of impairment was not made”.

Arunkalaivanan, who qualified as a doctor from the University of Madras in 1988, runs a private practice at BMI Priory Hospital in Birmingham and is employed as an NHS consultant obstetrician and gynecologist in Birmingham City Hospital. The consultation involving Patient A took place at BMI Edgbaston Hospital in Birmingham in October 2010. “I left the room that day and I just, it just felt so wrong. I could just not get the examination out of my head,” Patient A, who cannot be named for legal reasons, told the panel. According to ‘Court News UK’, when she complained to the hospital, the doctor had offered to apologise but she was also told that Indian doctors were trained to carry

out breast exams in that way. She made efforts to find out if the way he conducted the examination was how Indian doctors are trained, but was told otherwise by a nurse, the panel heard. The tribunal decided not to strike off Arunkalaivanan from the UK medical register in view of the medical services he can offer to the public (Times of India). ÂÂ The European Food Safety Authority says that the

artificial sweetener aspartame is safe at the levels currently used in food and drinks. Aspartame, sold as NutraSweet and Equal, has been used in soft drinks and other low–calorie or sugar–free foods for more than 25 years. The study ruled out a potential risk of aspartame causing damage to genes and causing cancer. It says there is no evidence that the sweetener harms the brain, the nervous system, or affects behavior or mental skills in children or adults.

ÂÂ Researchers who studied 256 individuals with

CKD for an average of 3.7 years found that physical activity was inversely related to kidney function decline in a graded fashion and to a degree that was stronger than previously reported in the general population. Each 60-minute increment in weekly physical activity was linked with a 0.5% slower decline per year in kidney function in the JASN study.

ÂÂ In a cohort study of 1030 adult elective cardiac

surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery, 5-year risk of death was 26.5% among patients who developed acute kidney injury (AKI) within 5 days of surgery and 12.1% among patients who did not develop AKI. After adjustment, patients with AKI had a 60% increased risk of dying within 5 years. AKI was associated with a statistically insignificant increased risk of myocardial infarction. The findings are published in Critical Care.

ÂÂ The US FDA has permitted marketing of the Cerena

Transcranial Magnetic Stimulator (TMS; eNeura Therapeutics), the first device approved to relieve pain caused by migraine headache with aura. The device is used by prescription after onset of pain associated with migraine with aura. Using both hands, the patient holds the device to the back of the head and, pressing a button, releases a pulse of magnetic energy that stimulates the occipital cortex, stopping or reducing the pain associated with this type of migraine.

ÂÂ In a study in Hepatology, patients with hepatitis

C and diabetes when treated with pegylated

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

785

Around the Globe interferon plus ribavirin had significantly lower cumulative 8-year incidence of end-stage renal disease (1.1% for treated, infected patients versus 9.3% for untreated patients and 3.3% for uninfected patients) and stroke (3.1% versus 5.3% and 6.1%, respectively). There was also a trend toward less acute coronary syndrome (4.1% versus 6.6% and 7.4%, respectively. ÂÂ In an analysis of over 2,700 participants in

the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study, Dr Michael Miedema (Minneapolis Heart Institute, MN) and colleagues found that the tallest subjects in the study had the least amount of coronary artery calcium (CAC).

Their study was published online December 11, 2013 in Circulation: Cardiovascular Imaging.

ÂÂ Statins can be used in the elderly, even in those

aged above 75 years. Reassurance regarding the cardiovascular benefits of statin therapy in this population group was provided by a new metaanalysis by the international Cholesterol Treatment Trialists’ Collaboration. The meta-analysis included 174,099 participants in 27 major, published, randomized controlled trials with a median follow– up of 4.9 years.

ÂÂ Vitamin D supplements for pregnant women and

their newborns increased the proportion of infants with serum vitamin D levels recommended by the Institute of Medicine (IOM), according to a doubleblind, placebo-controlled trial published online December 16 in Pediatrics.

ÂÂ Pregnant women, children, and infants should

consume only pasteurized milk and milk products, and the sale of raw milk should be banned in the United States, according to a new policy statement from the American Academy of Pediatrics (AAP).

The statement was published online December 16 in Pediatrics.

ÂÂ Aggressive metastatic prostate cancer cells express

high levels of the NAALADL2 (N-acetyl-L-aspartylL-glutamate peptidase-like 2) protein, which can serve as a diagnostic and prognostic biomarker for prostate cancer, report Hayley Whitaker, PhD, and colleagues at Cancer Research UK in Cambridge, United Kingdom November 18 in Oncogene.

ÂÂ Blood pressure, cholesterol, and glucose together

explained about half of the heightened risk of coronary heart disease (CHD) among individuals with a high body mass index (BMI) in a large review of 97 international studies. These three risk factors also explained three–quarters of the excess risk of stroke in overweight and obese individuals. Of

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the three risk factors, blood pressure was the most important, followed by glucose and cholesterol.

The study, by the Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects), was published online November 22, 2013 in the Lancet. ÂÂ Decreased endogenous estrogen levels are largely

unrelated to changes in cognitive ability and mood in postmenopausal women, according to research published online November 25 in the Proceedings of the National Academy of Sciences.

ÂÂ A low-fat diet and supplementation with fish oil

appears to reduce proinflammatory substances in the blood of prostate cancer patients, according to a new study. It also decreased the cell cycle progression (CCP) score, which is a measure used to predict cancer recurrence. The study was published online October 29 in Cancer Prevention Research. ÂÂ The FDA has approved an adjuvanted vaccine against the highly pathogenic H5N1 avian flu. The vaccine will not be available commercially, but will form part of the national stockpile in case the H5N1 flu develops into a human pandemic. The vaccine, dubbed Q-Pan H5N1, got a unanimous nod from the FDA’s vaccine advisory board in late 2012. The agency is not obliged to follow such advice but usually does. ÂÂ A new report The Heart of the Matter: Rethinking prevention of cardiovascular disease by the Economist Intelligence Unit investigates the health challenges posed by CVD. Despite greater recognition of the problem, every indication is that the global burden of the disease will get worse before it gets better. Greater collaboration is needed to prevent the disease. CVD is the world’s leading killer, according to the World Health Organization (WHO). It accounted for 30% of deaths around the globe in 2010. A joint Harvard University and World Economic Forum study estimated the total economic cost to be over US $850 bn per year predicted to reach US $1 tn by 2025. Dr Srinath Reddy, the president of the World Heart Federation, calls CVD “the dominant epidemic of the 21st century”. In India and China, the percentage of deaths caused by CVD increased by 20% between 1990 and 2010. The equivalent rate in the US and Western Europe fell by at least 20% during that same period, although CVD still accounts for 43% of all deaths in 2010, according to the WHO. The common feature of the disease across the world is its disproportionate impact on individuals from lower socioeconomic groups.

Around the Globe ÂÂ A noninvasive test that computes fractional flow

reserve from coronary CT angiography images was highly accurate in detecting ischemia, compared with anatomic interpretation from CT angiography or invasive coronary angiography, in a study of 254 patients and 484 vessels. The AUC for the new test was 0.82, significantly better than 0.63 for coronary CT angiography. The specificity nearly doubled when the HeartFlow test was used to compute fractional flow reserve from coronary CT angiography images (FFRCT), compared with coronary CT angiography assessment. FFRCT correctly reclassified 68% of false positives from CT angiography to true negatives.

ÂÂ Analysis of data from a large clinical cohort

has shown that children with systemic lupus erythematosus (SLE) had an increased risk for cancer, particularly for malignancies that were hematologic in origin. Among 1,020 patients younger than age 18 and followed for an average of 7.8 years, there were 14 cases of invasive cancer when three cases would have been expected, for a standardized incidence ratio (SIR) of 4.7. Three of the cases were hematologic, with two being nonHodgkin’s lymphoma (NHL) and one leukemia, for an SIR of 5.2 (Arthritis Research & Therapy).

ÂÂ Structural brain changes that eventually lead to

Alzheimer’s disease (AD) might date back to infancy in children who carry the apolipoprotein E (APOE) e4 allele, which is known to increase AD risk, a new study suggests. The study showed that babies carrying the APOE e4 risk allele have less white myelin water fraction (MWF) and gray matter volume in certain brain regions, and more in other regions, compared with babies who don’t carry this genetic variant. The observational study was published online November 25 in JAMA Neurology.

Formula of 80 to Prevent Heart Attack up to the Age of 80 Eighty percent of heart attacks up to the age of 80 can be prevented by learning the Formula of 80 as below. ÂÂ Keep your lower blood pressure, fasting sugar,

abdominal circumference, resting heart rate and LDL cholesterol levels all below 80.

ÂÂ Walk 80 minutes each day; brisk walk 80 minutes a

week with a speed of 80 steps per minute.

ÂÂ Eat less, not more than 80 gm/80 ml of caloric food in

one meal.

ÂÂ Do not eat carbohydrate-based refined cereals 80 days

in a year to reduce chances of heart attack.

ÂÂ Take vitamin D through sunlight 80 days in a year.

ÂÂ Do not drink alcohol and if you drink, take less than 80

ml of whiskey in a day or less than 80 gm of whiskey in a week.

ÂÂ Do not smoke or be ready for placement of stent

costing Rs. 80,000/–.

ÂÂ Give 80 minutes to yourself in a day. ÂÂ When clapping, clap 80 times. ÂÂ If you are a heart patient, ask your doctor to give 80

mg of aspirin and 80 mg of atorvastatin.

ÂÂ Donate blood 80 times in a lifetime to reduce chances

of heart attack.

ÂÂ Avoid an atmosphere of more than 80 db of noise

pollution.

ÂÂ While on treadmill, try to reach 80% of your heart rate. ÂÂ The introduction of cheaper, generic aromatase

inhibitors, used to prevent breast cancer recurrence, appears to have improved adherence, according to a new research presented at the annual San Antonio Breast Cancer Symposium.

ÂÂ Concomitant IV use of vancomycin and piperacillin/

tazobactam, regardless of extended or traditional infusion, appeared to result in acute kidney injury in roughly one out of every five inpatients. In a study presented at the American Society of Health-System Pharmacists, among 226 adult inpatients, no cases of nephrotoxicity were found among those treated with vancomycin alone, but 22.7% of those treated with a traditional infusion of concomitant vancomycin and piperacillin/tazobactam, as well as 19.6% of those given an extended infusion of the combination, experienced elevated creatinine levels to the point of toxicity (P<0.05).

ÂÂ Fewer than one in six patients treated with powerful

antibiotics for a Clostridium Difficile (C. Diff) infection actually had lab-confirmed infections despite high costs and negative outcomes of unnecessary treatments.

At a 240-bed hospital, over the course of 22 months‚ 1‚971 patients were treated with vancomycin and/ or metronidazole for a C. Diff infection, but only 292 of those patients had positive test results for C. Diff (American Society of Health-System Pharmacists).

ÂÂ Reductions in time to treatment followed the

development of more efficient treatment protocols for sepsis, but not after Computer Physician Order Entry (CPOE) systems were put in place. Tram Cat, PharmD, BCPS, of Cedars-Sinai Medical Center in Los Angeles, Calif., and colleagues reported at the midyear meeting of the American Society of Health –System Pharmacists that a combination of procedural updates, including Code Sepsis and nursing staff alerts, shortened the time between diagnosis and administration of antibiotics by 64% in non–ICU sepsis patients.

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forthcoming conferences

International Conferences International Conference on Yoga Research and Its Applications: Diabetes, Prevention and Education Date: 2-5 January 2014 Venue: Bengaluru, Karnataka, India Website: http://svyasa.org/news-events/20th-incofyra dec-19-22-2013/ 3rd Annual Building the Heart Team: Valve and Structural Heart Disease Conference Date: 16-19 January 2014 Venue: Ft. Lauderdale, FL, United States of America Website: http://www.mayo.edu/cme/cardiovasculardiseases-2014R190 The 8th International Conference on Brain Monitoring & Neuroprotection in the Newborn Date: 16-18 January 2014 Venue: Clearwater Beach, FL, United States of America Website: http://health.usf.edu/publichealth/pdf/Call_ for_Abstracts_Brain%20Monitoring_2014.pdf Pharmaceutical Microbiology Date: 20-21 January 2014 Venue: London, United Kingdom Website: http://www.smi-online.co.uk/goto/2014 pharma-microbiology2.asp 28th Annual San Diego International Conference on Child and Family Maltreatment Date: 28-31 January 2014 Venue: San Diego, California, United States of America Website: http://www.sandiegoconference.org INTERNATIONAL CONFERENCE ON FOOD, BIOLOGICAL AND MEDICAL SCIENCES (FBMS-2014) Date: 28-29 January 2014

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Venue: Bangkok, Thailand Website: http://www.iicbe.org/2014/01/28/37 Mayo Clinic Presents, Hawaii Heart: CaseBased Clinical Decision Making Using Echocardiography and Multimodality Imaging Date: 3-7 February 2014 Venue: Poipu Beach, Kauai, HI, United States of America Website: http://www.mayo.edu/cme/hawaiiheart2014 Summit for Clinical Ops Executives (SCOPE) 2014 Date: 4-6 February 2014 Venue: Miami, Florida, United States of America Website: http://www.scopesummit.com The 27th Annual Gravens Conference on the Physical and Developmental Environment of the High Risk Infant Date: 5-8 February 2014 Venue: Clearwater Beach, FL, United States of America Website: https://tinyurl.com/Gravens2014-webpage Making Sense of Dementia: Psychoanalytic Perspectives Date: 8 February 2014 Venue: London,United Kingdom Website: http://www.freud.org.uk/events/75385/ making-sense-of-dementia-/ 1-Week Hands-on Workshop on Human/ Cancer Cell Culture Techniques & MTT Assay Date: 9-15 February 2014 Venue: Pune, Maharashtra, India Website: http://www.icsccb.org/workshops cellculture workshop

emedinews inspiration

A Story for Passover

A

good Passover story should always involve cakes. Austrian baker Manfred Klaschka is the subject of this year’s story. He was in the news because of his most recent catalogue of cake designs, Klaschka is a pastry specialist.

Of course, Austrian pastries are famous the world over. Now, pastry baker Manfred Klaschka’s most recent catalogue of such tasty delights was in the news this week because it included cakes decorated with swastikas as well as one with a baby raising its right arm in a Nazi salute.

Herr Klaschka insists he is not a Nazi. After the news story broke, he even met with a Holocaust awareness group, and apologized for what he had done and he then baked a cake to say he was sorry a cake with Jewish and Christian symbols. The point of the story – the bit I found interesting is Herr Klaschka’s explanation for what he did.

“I see it was a mistake, anyone who knows me knows what kind of person I am. I am no Nazi”, said Klaschka, who had earlier said he was just a pastry maker fulfilling his customers wishes. Fulfilling his customers wishes? There is a market in Austria in 2011 for cakes with babies raising their arms in Nazi salutes, cakes with swastikas on them? There are parties where people serve such cakes? Maybe birthday parties for babies?

Of course there are such people, and there are such parties, and because of that, there is a market there is consumer demand for swastika cakes, which is why Herr Klaschka was happy to bake them and not only in Austria.

You may remember the case of the Campbell family from New Jersey.

When Kurt Waldheim was exposed as a war criminal his popularity rose. The neo–Nazi Freedom Party headed by the late Jorg Haider, won 27% of the vote in the 2000 elections and became part of the coalition government the first time since 1945 that Nazis had sat in a European government.

But this never happened in New Jersey, which is why I want to talk about the Campbell family. The Campbell family in New Jersey made the news back in 2008 when they tried to get a birthday cake made for their son — they have a son and two daughters — at the local Shop Rite in Holland Township. The store refused their request.

And the reason was that Mr. Campbell wanted the cake to read “Happy birthday Adolf Hitler”. Because, you see, his son’s name was Adolf Hitler Campbell. One of the daughters is named is named Joyce Lynn Aryan Nation Campbell. Well, you get the point.

When I read about the Austrian baker Manfred Klaschka, I thought here was a marketing opportunity for him. He would have happily baked a cake for the Campbell family.

So what does all this have to do with Passover?

This week, when we are forbidden to eat Sachertore or Linzer tort or even the delightfully named Punschkrapfen, we might want to pause and think about something we say every year at the Passover seder: ‘In every generation it is the duty of man to consider himself as if he had come forth from Egypt’.

Because in this generation, as in all others, there are those who order custom–made swastika cakes. There are those who name their children after Adolf Hitler.

And there are others who fire anti–tank missiles at school buses with Jewish children in them. Because there are those who are building nuclear weapons, having told the world that their intention is to wipe the Jewish state off the face of the earth. Because people like that make Pharaoh look like a nice guy. Because getting out of the house of bondage, out of slavery in Egypt, was not the end of the story for the Jewish people, but was the beginning.

It is a story of a never–ending struggle for freedom, for dignity, for respect, for human rights, that has universal resonance and meaning — for all people, everywhere, always.

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Medifinance

Medifinance ÂÂ

If your gross receipt is more than 15 lakhs, you need to get your accounts audited from a CA

ÂÂ

Cash donation of more than 10,000 not eligible for tax deduction under section 80G

ÂÂ

Incomes means salary/professional income, rental income, capital gains, business and professional income, interest income etc.

ÂÂ

Gifts from blood relations are exempt from tax, however, all other gifts in all if exceeding Rs. 50,000 is taxable as income from other sources.

ÂÂ

You can claim 50% of the amount donated as deduction provided you get a 80G certificate.

In specific situation, you can also claim 100% exemption.

ÂÂ

Residents having assets located outside India are required to furnish tax returns mandatorily from financial year 2011-12 onwards.

If your income is more than 50000 per annum, you need to have a PAN Card no.

ÂÂ

ÂÂ

All delayed payments of TDS interest is payable @ 1% each month or part of the month.

Always write your will. Don’t wait to write when you are old.

ÂÂ

ÂÂ

Business loan can be set off against capital gains not against salaried income.

Never receive more than Rs. 20000 in cash or given more than Rs. 20000 in cash for any expense.

ÂÂ

ÂÂ

Loss from gambling, horse race and speculations only can be adjusted against income from same business.

ÂÂ

You can only receive gifts from the immediate blood relatives.

ÂÂ

A person can make a gift of any property movable or immovable during his lifetime

ÂÂ

As per Chanakya, unethical money lasts only for 8 years.

ÂÂ

Never write off your property to your children while you are still alive.

■■■■

Peace of Mind Once, Buddha was walking from one town to another town with a few of his followers. This was in the initial days. While they were traveling, they happened to pass a lake. They stopped there and Buddha told one of his disciples, “I am thirsty. Do get me some water from that lake there.”

The disciple walked up to the lake. When he reached it, he noticed that some people were washing clothes in the water and, right at that moment, a bullock cart started crossing through the lake. As a result, the water became very muddy, very turbid. The disciple thought, “How can I give this muddy water to Buddha to drink!” So he came back and told Buddha, “The water in there is very muddy. I don’t think it is fit to drink.”

After about half an hour, again Buddha asked the same disciple to go back to the lake and get him some water to drink. The disciple obediently went back to the lake. This time he found that the lake had absolutely clear water in it. The mud had settled down and the water above it looked fit to be had. So he collected some water in a pot and brought it to Buddha.

Buddha looked at the water, and then he looked up at the disciple and said, “See what you did to make the water clean. You let it be… and the mud settled down on its own – and you got clear water… Your mind is also like that. When it is disturbed, just let it be. Give it a little time. It will settle down on its own. You don’t have to put in any effort to calm it down. It will happen. It is effortless.”

Source: eMedinewS

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mediLAW

Medicolegal Queries What are close–range and contact wounds?

Close-range wounds: When a firearm is discharged very close to or in contact with the skin surface, the gases produced by the explosion pass into the tissues with the bullet and cause considerable laceration of the skin and subcutaneous tissues. The entrance wound has a ragged appearance, especially over the skull where it may be stellate in appearance. There is usually some blackening and tattooing of the skin around the bullet entrance wound, while the hair in the region of the wound may be singed. Some skin burning and abrasion in relation to the hot gases may be present.

Contact wounds: In these wounds, the discharge passes into the tissues through the bullet entrance opening and powder deposits as well as blackening may be observed in the depths of the wound. The doctor attending the case must document all the findings in clinical sheet/medico-legal report.

A doctor prepared an MLC 10 years ago.

Later he went abroad and became an NRI. A court summon was recently sent to his home address in India and was received by the relatives. He cannot come from abroad for court appearance. What are the legal implications? ÂÂ MLC record does not contain the home address of

a doctor. The MLC was most likely made by the doctor in discharge of his official duties while he was working in the hospital concerned. The court probably asked the state/police to summon the doctor as witness. The police most likely went to the hospital, who probably found from their service records the home address of the doctor and supplied the same to the police.

ÂÂ The summon should not have been received by

the relatives when the doctor is not living at the address in the summon. If the relatives told the process server (the person who brought the summon) that the doctor lived abroad, he should not have delivered the summon to his relatives and should have told this fact to the concerned authorities.

ÂÂ It is everybody’s duty to assist in the proceedings of

the court. The duty to assist the court lies primarily

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on the hospital where the MLC was made. If the doctor who made the MLC is not available for any reason, it is the duty of the hospital to offer to send another doctor, preferably from the FMT department, to assist the court as a witness. ÂÂ Now that the summon has been received by the

relatives, the person who received the summon should appear before the court and inform it about the present address of the doctor for necessary action. The court would most likely ask the hospital to send somebody else as expert witness.

If the court feels necessary, it can order for a video conference to be arranged with the doctor living abroad.

Does running of a clinic by a physician at his residence amount to commercial activity? ÂÂ This question has recently been answered by the

Delhi HC in DR. D.V. CHUG versus STATE & ANR., Delhi HC, decided by SURESH KAIT, J., on 2-7-2012.

ÂÂ Para of this judgment is reproduced below:

“5. The issue arises in the instant petition, whether, running of clinic from the residential premises, would come in commercial activity”.

ÂÂ After

a detailed discussion of law and decided cases, the court observed as follows: “11. On considering the submissions of ld. counsel appearing for the parties, I am of the considered view that the professional establishment of a doctor cannot come within the definition of commercial activity. Commerce is that activity where a capital is put into; work and risk run of profit or loss. If the activities are undertaken for production or distribution of goods or for rendering material services, then it comes under the definition of commerce. The word ‘profession’ used to be confined to the three learned professions; the Church, Medicine and Law. There is a fundamental distinction between the professional activities and commercial activities”.

ÂÂ SUMMARY-Running of a clinic by a physician

at his residence amounts to a professional, not a commercial activity.

Source: Dr. MC Gupta

eMedi Quiz

Quiz Time 1.

All of the following features can be observed after the injury to axillary nerve except:

A.

Loss of rounded contour of shoulder

B.

Loss of sensation along lateral side of upper arm

C.

Loss of overhead abduction

D. Atrophy of deltoid muscle 2.

The primary role of chaperones is to help in:

A.

Protein synthesis

B.

Protein degradation

C.

Protein denaturation

C.

Epinephrine

D. Glucagon 4.

The cells belonging to the following type of epithelium are provided with extra reserve of cell membrane:

A. Transitional B.

Stratified squamous

C.

Stratified cuboidal

D.

Stratified columnar

D. Protein folding

5. An increase in which of the following parameters will shift the O2 dissociation curve to the left.

3.

A. Temperature

Which of the following is present intracellularly in muscle cells?

B.

Partial pressure of CO2

A. Insulin

C.

2,3 DPG concentration

B.

D.

Oxygen affinity of haemoglobin

Corticosteroid

Answers to eMedi Quiz Published in December 2013 Issue Q1. (D) Condyles of tibia.

Q2. (D) Pre-existing neurological deficits.

Q3. (D) Protein folding.

Q4. (C) Steroids.

Q5. (C) About 30 percent of your daily calories.

Send your answers to the Editor-Indian Journal of Clinical Practice.

E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

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lighter reading

Lighter Side of Medicine

The Master then asked the young lady to take another handful of salt and put it in the lake.

The two walked in silence to the nearby lake and when the apprentice swirled his handful of salt into the lake, the old man said, “Now drink from the lake.”

As the water dripped down the young lady’s chin, the Master asked, “How does it taste?” “Good!” remarked the apprentice. “Do you taste the salt?” asked the Master. “No,” said the young lady.

The Master said, “The pain of life is pure salt; no more, no less. The amount of pain in life remains the same, exactly the same. But the amount we taste the ‘pain’ depends on the container we put it into. So when you are in pain, the only thing you can do is to enlarge your sense of things…… Stop being a glass. Become a lake!”

Good friends care for each other… close friends understand each other… and true friends stay forever beyond words, beyond time.

Dr. Good and Dr. Bad Situation: A patient with rheumatoid arthritis was found to have high platelet count.

They are not linked

They are linked

©IJCP Academy

The old master instructed the unhappy young lady to put a handful of salt in a glass of water and then to drink it. “How does it taste?” the Master asked. “Very bad” said the lady.

Quote

INSPiRATIONAL

A Young Sad Lady

Lesson: Elevated platelet count usually means an immunoinflammation.

HUMOR As an English professor, my father would often write little notes on student essays. Often he worked late, and as the hours passed, his handwriting deteriorated. One day a student came to him after class with an essay that had been returned. “Mr. McDonald,” he said, “I can’t make out this comment you wrote on my paper.”

My father took the paper and, after studying it, sheepishly replied, “It says that you should write more legibly.”

Kidneys and Livers Two old men were arguing the merits of their doctors. The first one said, “I don’t trust your fancy doctor. He treated old Jake Waxman for a kidney ailment for nearly a year, and then Jake died of a liver ailment.” “So what makes you think your doctor is any better?” asked his friend.

“Because when my doctor treats you for a kidney ailment, you can be sure you’ll die of a kidney ailment.

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KK Aggarwal

ILLUSION

Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript Three complete sets of the manuscript should be – submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

–

The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

–

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

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

797

Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1.________________

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

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798

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

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

6. Suggestions for reviewers (name and postal address)

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

Indian Journal of Clinical Practice, Vol. 24, No. 8, January 2014

799

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

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