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Asian

Journal of

IJCP Group of Publications

CLINICAL CARDIOLOGY

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

Volume 14, Number 9, January 2012

Dr Deepak Chopra Chief Editorial Advisor Dr KK Aggarwal CMD, Publisher, Group Editor-in-Chief Dr Veena Aggarwal MD Group Executive Editor

from the desk of group editor-in-chief 293 CABG, PCI Guidelines Stress Collaboration

Dr Praveen Chandra Guest Editor, AJCC praveen.chandra@medanta.org Assistant Editor: Dr Nagendra Chouhan, Dr Dharmendar Jain

AJCC Speciality Panel Advisory Borad

International Dr Fayoz Shanl Dr Alain Cribier Dr Kohtian Hai Dr Tanhuay Cheem Dr Ayman Megde Dr Alan Young Dr Gaddy Grimes Dr Jung bo Geg Dr Rosli Mohd. Ali Dr S Saito National Dr Mansoor Hassan Dr RK Saran

Dr SS Singhal Dr Mohd. Ahmed Dr PK Jain Dr PK Gupta Dr Naresh Trehan Faculty Dr GK Aneja Dr Ramesh Thakur Dr Balram Bhargava Dr HK Bali Dr HM Mardikar Dr Sanjay Mehrotra Dr Vivek Menon Dr Keyur Parikh

original article 295 Comparative Study of Carotid, Aortic and Cardiopulmonary Baroreflexes

Dr Ajit Mullasari Dr Kirti Punamiya Dr MS Hiramath Dr VS Narain Dr SK Dwivedi Dr Raja Baru Panwar Dr Vijay Trehan Dr Rakesh Verma Dr Suman Bhandari Dr Ravi Kasliwal Dr Atul Abhyankar Dr Tejas Patel Dr Samir Dani

Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Jyoti Yadav

review article 298 Noncardiac Manifestations of Tetralogy of Fallot

IJCP Editorial Board

Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma, Dr Kamala Selvaraj ENT Dr VP Sood Cardiology Dr Praveen Chandra, Dr M Paul Anand, Dr SK Parashar Paediatrics Dr Swati Y Bhave, Dr Balraj Singh Yadav, Dr Vishesh Kumar Diabetology Dr Vijay Viswanathan, Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramachandran, Dr Samith A Shetty Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Anand Gopal Bhatnagar Editorial Anchor

KK Aggarwal

Apurva Pande, Neha Gupta, Sanjiv Gupta Dharmendra Jain

original study 303 Omega-3 Fatty Acids and Cardiovascular Disease

AP Jain, KK Aggarwal

Clinical Study 308 Hypocholesterolemic Effects of Lactobacillus acidophilus as A Dietary Supplement

M Vani, M Shiva Prakash, P Yashoda Devi

case report 315 Common Coronary Trunk from the Right Sinus of Valsalva Giving Origin to Right and Left Coronary Arteries

Monika Maheshwari, Chandra Prakash Tanwar


medilaw

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

317 Insight on Medicolegal Issues

expert’s opinion

Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com printer_ig@yahoo.com

318 Is there an Association between Hypertension and Depression?

© Copyright 2012 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

J Nagpal, KK Aggarwal

practice guidelines

Editorial Policies

319 ACCP Releases Statement on Dyspnea Treatment in Patients with Advanced Lung or Heart Disease

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.

Revisiting 2011 321 Top Cardiology News of 2011

lighter reading 322 Lighter Side of Medicine

Note: Asian Journal of Clinical Cardiology 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.

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from the desk of 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 Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

CABG, PCI Guidelines Stress Collaboration 

A multidisciplinary heart team - including an interventional cardiologist and a cardiac surgeon - should work together to develop a care plan for each patient with coronary artery disease (CAD), according to updated guidelines from the American College of Cardiology Foundation and the American Heart Association and published in the Dec. 6 issue of the Journal of the American College of Cardiology. The team should review the patient’s medical condition and coronary anatomy and then determine whether percutaneous coronary intervention (PCI) and/or coronary artery bypass grafting (CABG) were feasible and reasonable. After discussing options with the patient, a treatment strategy should be selected, according to the guidelines. Support for this approach comes from reports that patients with complex CAD referred specifically for PCI or CABG in concurrent trial registries have lower mortality rates than those randomly assigned to PCI or CABG in controlled trials. The team concept was included as a Class I recommendation for patients with unprotected left main or complex CAD. Another new recommendation in the guideline is the use of the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score when making treatment decisions for patients with multivessel disease. This system uses angiography results to estimate the extent and complexity of arterial disease and gives a more objective way to guide decision making. The guidelines say that PCI is a reasonable alternative to CABG in stable patients with left main artery CAD, low-risk of PCI complications and a high-risk for adverse surgical outcomes. They also confirm the superiority of CABG compared to both medical therapy and PCI in patients with three-vessel disease. Specific to CABG, the experts also weighed in on the use of antiplatelet therapy both before and after the operation. The guidelines suggest aspirin should be given to CABG patients preoperatively. In those undergoing elective procedures, clopidogrel and ticagrelor should be stopped five days before elective surgery. In emergent situations, they should be discontinued for at least 24 hours if possible. After the operation, aspirin should be started within the first six hours if not already begun before the procedure. Clopidogrel was termed a ‘reasonable alternative’ in patients allergic to aspirin. The PCI group also addressed antiplatelet therapy. The committee simplified the regimen for aspirin use, suggesting using 81 mg daily following PCI instead of higher maintenance doses. They also provided a Class I recommendation for dosing ticagrelor for at least 12 months following insertion of both drug-eluting and bare metal stents. Source: MedPage Today

Asian Journal of Clinical Cardiology, Vol. 14, No. 9, January 2012

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review article 7.

Touliatou V, Fryssira H, Mavrou A, Kanavakis E, Kitsiou-Tzeli S. Clinical manifestations in 17 Greek patients with Goldenhar syndrome. Genet Couns 2006;17(3):359-70.

8.

Temtamy SA, McKusick VA. The Genetics of Hand Malformations. Alan R Liss, Inc: New York; 1978.

9.

Zaka-ur-Rab Z, Mittal S. Optic nerve head drusen in Goldenhar syndrome. JK Science 2007;9(1):33-4.

10. Poland A. Deficiency of the pectoral muscles. Guy’s Hosp Rep 1841;6:191-3. 11. Clarkson P. Poland’s syndactyly. Guys Hosp Rep 1962;111:335-46. 12. David TJ. Nature and etiology of the Poland anomaly. N Engl J Med 1972;287(10):487-9. 13. Bouvet JP, Leveque D, Bernetieres F, Gros JJ. Vascular origin of Poland syndrome? A comparative rheographic study of the vascularisation of the arms in eight patients. Eur J Pediatr 1978;128(1):17-26. 14. Briner V, Thiel G. Hereditary Poland syndrome with megacalycosis of the right kidney. Schweiz Med Wochenschr 1988;118(23):898-903. 15. Mace JW, Kaplan JM, Schanberger JE, Gotlin RW. Poland’s syndrome. Report of seven cases and review of the literature. Clin Pediatr (Phila) 1972;11(2):98-102.

16. Tentamy SA, McKusick VA. The genetics of hand malformations. Alan R. Liss, New York 1978:p.301-22. 17. Castilla EE, Paz JE, Orioli-Parreiras IM. Syndactyly: frequency of specific types. Am J Med Genet 1980;5(4):357-64. 18. Temtamy SA, Aglan MS. Brachydactyly. Orphanet J Rare Dis 2008;3:15. 19. Shprintzen RJ, Goldberg RB, Lewin ML, Sidoti EJ, Berkman MD, Argamaso RV, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J 1978;15(1):56-62. 20. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 1997;34(10):798-804. 21. Shprintzen RJ. Velo-cardio-facial syndrome: 30 years of study. Dev Disabil Res Rev 2008;14(1):3-10. 22. Théveniau-Ruissy M, Dandonneau M, Mesbah K, Ghez O, Mattei MG, Miquerol L, et al. The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning. Circ Res 2008;103(2):142-8.

Asian Journal of Clinical Cardiology, Vol. 14, No. 9, January 2012

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original article

Comparative Study of Carotid, Aortic and Cardiopulmonary Baroreflexes Jyoti Yadav

Abstract The present study was conducted to elicit the response of various baroreflexes in the maintenance of mean arterial pressure (MAP) and heart rate (HR). There was a highly significant rise in MAP immediately after denervation of carotid, aortic and cardiopulmonary baroreflexes (p < 0.001). Significant increase in HR was observed with section of carotid and cardiopulmonary baroreflex pathways (p < 0.001). Although cutting of aortic nerves also led to significant increase in HR but it was less as compared to other baroreflexes. Carotid baroreflex was found to have major role in controlling MAP and cardiopulmonary baroreflex in controlling HR. Keywords: Baroreceptors, heart rate, mean arterial pressure

B

aroreflexes are a vital and major mechanism in regulation of blood pressure (BP) and heart rate (HR). They participate very effectively in maintaining BP and HR with postural changes1,2 and in response to hemorrhage.3 Vestibulosympathetic reflex defends against orthostatic challenges in humans by increasing sympathetic discharge.4 Two of the central observations in reflex control of circulation are that stimulation of baroreceptors decreases BP5 and that with destruction of baroreceptors (sinoaortic denervation), there is greatly increased BP variability.6-8 Selective sinoaortic deafferentiation (cutting the carotid sinus, the aortic and common carotid nerves) leads to temporary elevation of BP, HR and cardiac output which rapidly can return to baseline.9 The aortic depressor nerve stimuli produce larger depressor response than sinus stimuli,10 whereas activation of cardiopulmonary receptors results in reflex bradycardia, vasodilation and sympathoinhibition. In view of the importance of baroreflex system in our day-to-day life, the present investigation was conducted to determine the variations in circulatory vitals just after denervation of these reflex mechanisms.

Associate Professor Dept. of Physiology, Pt. BD Sharma PGIMS, Rohtak, Haryana Address for correspondence Dr Jyoti Yadav 30/9J, Medical Enclave Rohtak -124 001, Haryana

Material And Methods The study was conducted in 20 rabbits of either sex with mean weight 1.86 ± 0.08 kg. The rabbits were anesthetized with nembutal 30 mg/kg body weight through marginal vein of pinna. The animal was kept in supine position, tracheostomy was performed and femoral artery and vein were cannulated. The femoral artery cannula was connected to pressure transducer to record the BP on polyrite (Recorder Medicare System Ambala Inco.). Aortic nerves and vagus nerves were isolated in neck. Continuous electrocardiographic monitoring was performed throughout the experiment. In every rabbit, basal HR and mean arterial pressure (MAP) were recorded. (a) Then both sides aortic nerves were sectioned in midcervical region and immediate changes in MAP and HR were recorded. The BP and HR were allowed to stabilize. (b) Carotid sinuses denervation was then/done on both sides by stripping and the MAP and HR changes were recorded. The MAP and HR were allowed to stabilise. (c) Lastly, vagotomy was performed on both sides in midcervical region and immediate changes in MAP and HR were recorded. Results (a) Immediately after cutting of the aortic nerves on both sides, MAP increased to 108.38 ± 27.38 from the basal value of 98.19 ± 29.57, which was highly significant (p < 0.001). (b) While after denervating both the carotid sinuses, MAP increased to 123.09 ± 20.03 from the basal 91.37 ± 24.46 and was found to be highly significant (p < 0.001). (c) After bilateral vagotomy, MAP increased

Asian Journal of Clinical Cardiology, Vol. 14, No. 9, January 2012

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Original article Table 1. Changes in MAP (mmHg) after Denervation of Various Baroreflexes in Rabbits (n = 20) (Mean ± SEM) Control

Immediately

Mean increase after denervation

Mean increase

p value

(a) After cutting bilateral aortic nerves

98.19 ± 29.57

108.38 ± 27.38

15.58 ± 3.62

<0.001

(b) After denervating bilateral carotid sinuses

91.37 ± 24.46

123.09 ± 20.03

31.71 ± 5.31

<0.001

(c) After bilateral vagotomy

81.74 ± 21.90

98.73 ± 29.55

16.98 ± 4.18

<0.001

Table 2. Changes in HR (Beats/Min) after Denervation of Various Baroreflexes in Rabbits (n = 20) (Mean ± SEM) Control

Immediately after denervation

Mean increase

p value

(a) After cutting bilateral aortic nerves

248.2 ± 20.74

249.5 ± 21.58

1.3 ± 0.4

<0.02

(b) After denervating bilateral carotid sinuses

215.5 ± 31.67

226.1 ± 32.64

10.6 ± 2.06

<0.001

(c) After bilateral vagotomy

208.7 ± 41.60

221.1 ± 40.37

12.4 ± 1.13

<0.001

to 98.73 ± 29.55 from the basal 81.74 ± 21.90 and found highly significant (p < 0.001). However, the maximum rise in MAP was seen after carotid sinus denervation (Table 1). (a) After cutting both the aortic nerves, the HR increased to 249.5 ± 21.58 from the basal 248.2 ± 20.74, which was significant (p < 0.02). (b) While after denervating both the carotid sinuses, HR increased to 226.1 ± 32.64 from the basal 215.5 ± 31.67, which was highly significant (p < 0.001). (c) After bilateral vagotomy, HR increased to 221.1 ± 40.37 from the basal 208.7 ± 41.60 and was found to be highly significant (p < 0.001). Therefore, the maximum effect on HR was seen after bilateral vagotomy among (a), (b) and (c) experiments conducted (Table 2). DISCUSSION Carotid sinus reflex has dominant role when three systems interact and ineffectiveness of chemoreceptor stimulation when carotid or cardiopulmonary inhibition is maximal.11 In our study also, alteration in MAP after carotid sinus baroreceptor denervation was maximum as compared to post-aortic nerves section and bilateral vagotomy indicating carotid sinuses play a dominant role in controlling MAP. Pillsbury et al reported that pressor effect of severing both cervical vagus was duplicated by freezing both intrathoracic vagus at levels of cardiac and pulmonary afferent vagal fibers.12 Efficacy of the baroreflex mechanisms has also been observed in response to hemorrhage. Hosomi and Sagawa observed the fall in MAP after hemorrhage

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Asian Journal of Clinical Cardiology, Vol. 14, No. 9, January 2012

was maximum after carotid sinus denervation plus vagotomy followed by carotid sinus denervation only and minimal fall in MAP was seen after vagotomy alone.13 Edis observed that with only carotid reflex being operative, hemorrhage caused a decrease of 14% in MAP and with only aortic reflex, operative MAP decreased by 38%.14 Bishop and Barron observed that vagal block in presence of intact arterial baroreceptors caused a significant increase in MAP (22 ± 2 mmHg) and cardiac output (505 ± 90 ml/kg), while in absence of functional arterial baroreflexes, vagal block resulted in a significantly greater increase in MAP (49 ± 10 mmHg). They also observed that vagal block in presence of intact arterial baroreceptors caused a significant increase in HR (82 ± 6 beats/min), while in absence of functional arterial baroreflexes, vagal block resulted in significantly less response in HR.15 Natalie and DeCuir found that vagus nerves have more effect on cardiac slowing than does sympathetic nerve inhibition.16 In our study also, bilateral vagotomy led to maximum rise in HR (p < 0.001). Green et al showed tachycardia after denervating carotid sinus and after sectioning depressor nerves a similar type of tachycardia was observed in vagotomized animals.17 In the present study also, a highly significant tachycardia was observed after carotid sinuses denervation (p < 0.001), which was less as compared to postbilateral vagotomy. After cutting both aortic nerves, the HR also increased significantly (p < 0.02). James and Daly Mde reported that vasomotor response elicited by combined stimulation of carotid sinus and aortic arch


Original article baroreceptor was greater than either response resulting from their separate stimulation.18 Edis and Shepherd proved that section of both aortic nerves, after bilateral carotid sinus nerve section abolished the reflex decrease in HR and systemic arterial BP caused by distension of isolated aortic arch in dogs and hypertensive response to NaCN injected into aortic root.19

6.

Jacob HJ, Ramanthan A, Pan SG, Brody MJ, Myers GA. Spectral analysis of arterial pressure lability in rats with sinoaortic deafferentation. Am J Physiol 1995;269 (6 Pt 2):R1481-8.

7.

Schreihofer AM, Sved AF. Use of sinoaortic denervation to study the role of baroreceptors in cardiovascular regulation. Am J Physiol 1994;266(5 Pt 2):R1705-10.

8.

Sved AF, Schreihofer AM, Kost CK Jr. Blood pressure regulation in baroreceptor-denervated rats. Clin Exp Pharmacol Physiol 1997;24(1):77-82.

9.

Kezdi P. Kordenat RK. In The Nervous System in Arterial Hypertension. Julins S, Esler MD, Thomas CC (Eds.), Springfield 1976:p.207.

Conclusion Aortic nerves, carotid sinuses and vagus nerves, all have significant role in controlling MAP and HR. Further, carotid baroreflex was noted to have major role in controlling MAP and cardiopulmonary baroreflex in controlling HR. CLINICAL SIGNIFICANCE Baroreceptors are the vital mechanism which act within seconds to minutes in regulation of HR and BP between the 60-200 mmHg. This is of clinical significance in hemorrhage during accidents and surgery, postural hypotension, vasovagal shock, syncope, heart failure and myocardial infarction in a variety of ways. These should also be handled with care during neck and chest surgeries to avoid, alarming change in HR and BP. REFERENCES

10. Dworkin BR, Dworkin S, Tang X. Carotid and aortic baroreflexes of the rat: I. Open-loop steady-state properties and blood pressure variability. Am J Physiol Regul Integr Comp Physiol 2000;279(5):R1910-21. 11. Mancia G, Shepherd JT, Donald DE. Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs. Am J Physiol 1976;230(1):19-24. 12. Pillsbury HR 3rd, Guazzi M, Freis ED. Vagal afferent depressor nerves in the rabbit. Am J Physiol 1969;217(3):768-70. 13. Hosomi H, Sagawa K. Sinovagal interaction in arterial pressure restoration after 10% hemorrhage. Am J Physiol 1979;237(3):R203-9. 14. Edis AJ. Aortic baroreflex function in the dog. Am J Physiol 1971;221(5):1352-7.

Jacobsen TN, Morgan BJ, Scherrer U, Vissing SF, Lange RA, Johnson N, et al. Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress. Circ Res 1993;73(2):367-78.

15. Bishop VS, Barron K. In: Arterial Baroreceptor and Hypertension. Sleight P (Ed.), Oxford University Press: New York 1980:p.91.

2.

Singh P, Khurana I, Yadav J. Role of vagal and sinoaortic baroreflexes in circulatory adjustments to passive head up tilt. Indian J Med Sci 1992;46(4):112-8.

3.

Singh PI, Khurana I, Yadav J. Role of vagal and sinoaortic baroreflexes in restoration of arterial pressure after acute mild haemorrhage in rabbits. Indian J Physiol Pharmacol 1991;35(3):159-64.

17. Green MF, De Groat AF, McDonald CH. Observations on denervation of carotid sinuses and section of depressor nerves as a method of producing arterial hypertension Observations on denervation of carotid sinuses and section of depressor nerves as a method of producing arterial hypertension. Am J Physiol 1935;110:513-9.

4.

Ray CA. Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans. Am J Physiol Heart Circ Physiol 2000;279(5): H2399-404.

18. James JE, Daly Mde B. Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in the dog. J Physiol 1970;209(2):257-93.

5.

Shoukas AA. Overall systems analysis of the carotid sinus baroreceptor reflex control of the circulation. Anesthesiology 1993;79(6):1402-12.

19. Edis AJ, Shepherd JT. Selective denervation of aortic arch baroreceptors and chemoreceptors in dogs. J Appl Physiol 1971;30(2):294-6.

1.

16. Alexander N, Decuir M. Role of aortic and vagus nerves in arterial baroreflex bradycardia in rabbits. Am J Physiol 1963;205:775-80.

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review article

Noncardiac Manifestations of Tetralogy of Fallot Apurva pande*, neha gupta**, sanjiv gupta†, dharmendra jain‡

Abstract Tetralogy of Fallot is one of the commonest congenital cyanotic heart disease affecting children older than one year of age. Apart from its classical features it is associated with certain extracardiac manifestations, which occur in varying frequency. They include CATCH22 monosomy, Down’s syndrome, velocardiofacial abnormalities, CHARGE syndrome, Goldenhar syndrome (Occulo-auriculo-vertebral), Poland syndrome, syndactyly, brachydactyly and hypoplasia of ipsilatral hand. Keywords: Tetralogy of Fallot, Down’s syndrome, velocardiofacial abnormalities, CHARGE syndrome, Goldenhar syndrome, Poland syndrome

Tetralogy of Fallot

Velocardiofacial abnormalities

Fallot’s tetralogy (ToF) is the commonest congenital cyanotic heart disease in children above the age of one year.

Hypoplasia of ipsilateral hand.

Consists of:

CATCH 22 is a medical acronym for cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia, and a variable deletion on chromosome 22q11. The deletion within the chromosome region of 22q11 may occur in patients with dysmorphologic and cardiological syndromes.2

 

Ventricular septal defects (infracristal type). Right ventricular outflow tract Infundibular pulmonary stenosis.

Overriding of aorta.

Right ventricular hypertrophy.

obstruction-

The basic abnormality contributing to each of these features is anterior and cephalad deviation of the outlet septum, which is malaligned with respect to the trabecular septum. The various extracardiac manifestations associated with ToF are:1 

CATCH 22 monosomy

Down’s syndrome

CHARGE

Goldenhar syndrome (Occulo-auriculo-vertebral)

Poland syndrome

Syndactyly

Brachydactyly

*Junior Resident II, Dept. of Medicine, Subharti Medical College, Meerut **Senior Orthodontics, GTB Hospital, New Delhi †Associate Consultant, Max Hospital, New Delhi ‡Assistant Professor, Dept. of Cardiology, Banaras Hindu University, Varanasi Address for correspondence Dr Sanjiv Gupta Associate Consultant, Max Hospital, New Delhi E-mail: sanjivbhucardio@yahoo.co.in

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CATCH 22 Monosomy

Down’s Syndrome Down syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. Often, Down syndrome is associated with some impairment of cognitive ability and physical growth, and a particular set of facial characteristics. Many of the common physical features of Down syndrome may also appear in people with a standard set of chromosomes, including microgenia (an abnormally small chin),3 an unusually round face, macroglossia (protruding or oversized tongue),4 an almond shape to the eyes caused by an epicanthic fold of the eyelid, upslanting palpebral fissures (the separation between the upper and lower eyelids), shorter limbs, a single transverse palmar crease (a single instead of a double crease across one or both palms), poor muscle tone and a larger than normal space between the big and second toes. Individuals with Down syndrome have a high-risk of development of congenital heart defects (endocardial cushion defects, ToF), gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea and thyroid dysfunctions.


review article CHARGE Syndrome CHARGE is an acronym used for: C - Coloboma of the eye, central nervous system anomalies H - Heart defects A - Atresia of the choanae R - Retardation of growth and/or development G - Genital and/or urinary defects (Hypogonadism) E - Ear anomalies and/or deafness. CHARGE syndrome was formerly referred to as CHARGE association, which indicates a nonrandom pattern of congenital anomalies that occurs together more frequently than one would expect on the basis of chance.5 Very few people with CHARGE will have 100% of its known features.6 Association with ToF has been reported in some cases. Goldenhar Syndrome (Occulo-AuriculoVertebral) Goldenhar syndrome (also known as Oculo-AuriculoVertebral [OAV] syndrome) is a rare congenital defect characterized by anomalous development of the first and second branchial arch7 leading to incomplete development of the ear, nose, soft palate, lip and mandible. Common clinical manifestations include limbal dermoids, preauricular skin tags and strabismus.8 The characteristic features of Goldenhar syndrome like the incompletely developed ear, nose, soft palate, lip and mandible are usually present ipsilaterally. Some patients might have growing tissues with internal organs, especially heart, kidneys and lungs.9 Association with ToF is known in some cases. Poland Syndrome Poland syndrome was first described in 1841 by Sir Alfred Poland in the Guy’s Hospital Gazette while still a medical student based on findings of one cadaver dissection.10,11 The syndrome is characterized by congenital aplasia of the sternocostal head of the pectoralis major muscle associated with ipsilateral hand deformities.12 This rare entity is referred to as Poland’s syndrome or Poland’s syndactyly.13-15 In a few cases of Poland’s syndrome, features like absence of digits, brachydactyly, hypoplasia of wrist and/or hand, hypoplasia of forearm, hypoplasia of arm, thoracic cage defects, herniation of lung, axillary web or band,

absence of nipple and some genitourinary abnormalities have been reported.12,15 The absence of the sternal head of the pectoralis major muscle is considered the minimal expression of this syndrome. Skin of the area is hypoplastic with a thinned subcutaneous layer, and the axillary hair may be absent. Skeletal deformities may involve absence of portions of the ribs or costal cartilages anteriorly. In severe cases, anterior lung herniation may be present. The scapula may be smaller with winging; this is termed Sprengel deformity.12 The upper extremity also may be hypoplastic. The upper arm, forearm and fingers may be shortened, which is termed brachy-symphalangism. Simple, complete or incomplete syndactyly can also be found in patients with Poland syndrome. Temtamy and McKusick reported a child with Poland defect and ipsilateral renal hypoplasia.16 Subsequently, Mace et al (1972) found renal agenesis in one of their seven cases of Poland anomaly. This was also found by Miller and Miller (1975) in a child with absent pectoralis major muscle, without digital abnormality, who developed acute lymphoblastic leukemia. This reflects that a newborn who is suspected as a case of Poland’s syndrome must undergo a renal ultrasound and urographic studies to rule out any kidney involvement. Syndactyly It is a condition, where two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans. Isolated syndactyly is one of the most common congenital malformations of the hands and feet. On the basis of an anatomic approach, isolated syndactyly has been subdivided into five types.16 Syndactyly type 1 (SD1 [MIM 185900]), also named zygodactyly,’ is inherited as an autosomal dominant trait and accounts for the majority of isolated syndactylies, with an incidence of »2-3/10,000 in newborns (Castilla et al 1980; Tentamy 1990).17 In this common type of syndactyly, there is usually complete or partial webbing between the third and fourth fingers and the second and third toes, with occasional involvement of other digits. Syndactyly can be classified as either simple or complex and as complete or incomplete. 

In simple syndactyly, adjacent fingers or toes are joined by soft tissue. In complex syndactyly, the bones of adjacent digits are fused. The kangaroo exhibits complex syndactyly.

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review article 

In complete syndactyly, the skin is joined all the way to the tip of the finger. In incomplete syndactyly, the skin is only joined part of the distance to the fingertip.

Simple syndactyly can be full or partial, and is present at birth (congenital). In early human fetal development, webbing (syndactyly) of the toes and fingers is normal. At about 16 weeks of gestation, apoptosis takes place and an enzyme dissolves the tissue between the fingers and toes, and the webbing disappears. In some fetuses, this process does not occur completely between all fingers or toes and some residual webbing remains. Complex syndactyly occurs as part of a syndrome (such as Apert’s syndrome) and typically involves more digits and with complex syndactyly. Fenestrated syndactyly means the skin is joined for most of the digits but in a proximal area there is gap in the syndactyly with normal skin. This type of syndactyly is found in amniotic band syndrome. Brachydactyly The term brachydactyly is derived from the ancient Greek (brachy -short; dactylos-digit) meaning shortening of digits. It occurs due to abnormal development of phalanges or metacarpals or both. Brachydactyly is one of the 10 categories of hand malformations classified by Temtamy and McKusick.16 The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is inherited, either as an autosomal dominant or autosomal recessive trait. It can occur either as an isolated malformation or as a part of a complex malformation syndrome.18 Velocardiofacial Syndrome Velocardiofacial syndrome (VCFS) is a genetic condition, which results from abnormal pharyngeal arch development that causes defective development of the parathyroid glands, thymus and conotruncal region of the heart. Shprintzen and colleagues first described the syndrome in 1978.19 Velocardiofacial syndrome is associated with more than 180 different clinical features, with no single anomaly present in every patient. Individuals affected may present with structural or functional palatal abnormalities, cardiac defects, unique facial characteristics, hypernasal speech, hypotonia and defective thymic development. An estimated 75% of patients with velocardiofacial syndrome have cardiac anomalies.20 The cardiac defects are usually of the conotruncal type, which occur secondary to abnormal development of the outflow

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portion of the developing heart. The most common cardiac defects include interrupted aortic arch type B (50%), truncus arteriosus (34.5%) and ToF (16%). Palatal abnormalities predispose to speech and feeding difficulties. The defective thymic development is associated with impaired immune function. This condition predisposes the patient to an increased risk of infection and in some leads to development of autoimmunity. Parathyroid and immune deficiencies can progress or resolve with time. Affected individuals may also present with learning disabilities, overt developmental delay, psychiatric disorders and renal and musculoskeletal defects. This congenital disorder is caused by a deletion (microdeletion) at the q11.2 band, which is located on the long arm (q) of chromosome 22. In 90% of cases, the disorder occurs as the result of a new mutation in the form of a de novo 3-megabase microdeletion or translocation. This 3-megabase microdeletion encompasses a region that contains 40 genes.21 These genes have a role in organ development, including the heart and the central nervous system. These genes likely affect coronary artery development, given the number of coronary artery abnormalities associated with conotruncal defects.22 Hypoplasia of Ipsilatral hand Hypoplasia of ipsilateral hand has also been reported in certain cases in association with ToF. References 1.

Perloff JK. Clinical recognition of congenital heart disease. 5th edition, WB Saunders: Philadelphia 2003: 1-5.

2.

Alikaşifoğlu M, Malkoç N, Ceviz N, Ozme S, Uludoğan S, Tunçbilek E. Microdeletion of 22q11 (CATCH 22) in children with conotruncal heart defect and extracardiac malformations. Turk J Pediatr 2000;42(3):215-8.

3.

Weiss M. Conditional love: parents’ attitudes toward handicapped children. Greenwood Publishing Group Inc. 1994:p.94.

4.

Belfer ML. Discussion on: Lemperle G, Radu D: Facial plastic surgery in children with Down’s syndrome. J Plast Reconstruct Surg 1980;66:343-4.

5.

Blake KD, Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS, et al. CHARGE association: an update and review for the primary pediatrician. Clin Pediatr (Phila) 1998;37(3):159-73.

6.

Pagon RA, Graham JM Jr, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr 1981;99(2):223-7.



original study

Omega-3 Fatty Acids and Cardiovascular Disease AP Jain*, KK aggarwal**

Abstract Cardioceuticals are nutritional supplements that contain all the essential nutrients including vitamins, minerals, omega-3-fatty acids and other antioxidants like a-lipoic acid and coenzyme Q10 in the right proportion that provide all round protection to the heart by reducing the most common risks associated with the cardiovascular disease including high low-density lipoprotein cholesterol and triglyceride levels and factors that contribute to coagulation of blood. Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Omega-3 fatty acids are also used to treat hyperlipidemia and hypertension. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g/day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2-4 g/day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids. Keywords: Cardioceuticals, omega-3 fatty acids, cardioprotection, eicosapentaenoic acid, docosahexaenoic acid

C

ardioceuticals are nutritional supplements which nourish and protect the heart. While vitamins benefit the heart because of their antioxidant property, they do not provide overall cardioprotection, it is the cardioceuticals which act by providing overall protection. This is achieved by increasing oxygen supply, protection of artery walls and prevention of clots, antioxidation, maintaining healthy rhythm of the heart and lowering of cholesterol. Some of the important risk factors that need to be addressed by a cardioceutical include low-density lipoprotein (LDL) cholesterol levels, oxidative damage and effects of reactive oxygen species. They reduce the risk of sudden death, heart attack, prevent abnormal heart rhythms and strokes in cardiovascular disease patients. The build-up of atherosclerotic plaques can also be prevented by the use of these nutritional supplements. An ideal cardioceutical should contain all the essential nutrients including vitamins, minerals, omega-3-fatty acids and other antioxidants like a-lipoic acid (ALA) and coenzyme Q10 in the right proportion that will provide all round protection to the heart by reducing the most common risks associated with the cardiovascular disease including high LDL cholesterol and triglyceride levels and factors that contribute to

*Professor and Head Dept. of Medicine, MGIMS, Wardha **Senior Physician and Cardiologist Moolchand Medcity, New Delhi

coagulation of blood. The focus of this article is on role of omega-3 fatty acids in cardiac protection. Omega-3 fatty acids and cardioprotection Over the past 20 years, there has been a dramatic increase in the scientific scrutiny of and public interest in omega-3 and omega-6 fatty acids and their impact on personal health. Omega-3 fatty acids possess antiinflammatory, antiarrhythmic and antithrombotic properties; omega-6 fatty acids are proinflammatory and prothrombotic. Increased consumption of vegetable oils high in omega-6 fatty acids (such as corn, safflower, sunflower and cottonseed oils) and meats from animals that were fed grains high in omega-6 fatty acids has drastically shifted the dietary ratio of omega-6 to omega-3 fatty acids from an estimated 1:1 in the early human diet to approximately 10:1 in the typical modern American diet.1 Omega-3 and omega-6 fatty acids are essential because they are not synthesized by the body and must be obtained through diet or supplementation. Through an inefficient enzymatic process of desaturation (the rate of conversion is <1%), ALA produces eicosapentaenoic acid (EPA) (20 carbons) and docosahexaenoic acid (DHA) (22 carbons), precursors to a group of eicosanoids (prostaglandins, thromboxanes and leukotrienes) that are anti-inflammatory, antithrombotic, antiarrhythmic and vasodilatory. The longer chain fatty acid derivative of linoleic acid is arachidonic acid (20 carbons), which

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Original Study is a precursor to a different group of eicosanoids that are proinflammatory and prothrombic. ALA and linoleic acid use and compete for the same enzymes in the production of their longer chain fatty acids, EPA and arachidonic acid. The ingestion of fish and fish oil provides EPA and DHA directly, therefore avoiding the competition for enzymes to convert ALA to EPA.1

formation. Two important cells in the development of an atherosclerotic plaque are smooth muscle cells and macrophages. Platelet-derived growth factor is a key chemoattractant and mitogen for smooth muscle cells and macrophages. Platelet-derived growth factor production and messenger RNA synthesis are decreased by the ingestion omega-3 fatty acids.9

Mechanism of cardioprotection

Lipid Metabolism

Omega-3 fatty acids have been shown to be cardioprotective due to multiple mechanisms.

The effect on lipid metabolism is predominantly antiatherogenic. Consuming fish oil (a rich source of EPA) has been shown to lower total cholesterol and triglyceride concentrations by inhibiting very LDL and triglyceride synthesis in the liver.10 Large doses of fish oil have been shown to have profound effects in reducing triglyceride levels in hypertriglyceridemic patients. Apolipoprotein B production is also reduced by fish oil consumption compared with vegetable oils not containing omega-3 polyunsaturated fatty acids.10

Antiarrhythmic Effect It is thought that omega-3 fatty acids stabilize the electrical activity of cardiac myocytes by inhibiting sarcolemmal ion channels, resulting in a prolonged relative refractory period.2

Antithrombotic Properties The omega-3 fatty acids demonstrate significant antithrombotic properties. EPA has been shown to inhibit the synthesis of thromboxane A2, a prostaglandin that causes platelet aggregation and vasoconstriction.3 Ingestion of EPA has also been shown to reduce platelet adhesion and reactivity, which manifests itself as increased bleeding time and decreased adhesion of platelets to glass beads.4 Reductions in fibrinogen and increases in tissue plasminogen activator are some of the other antithrombotic effects which have been reported.5

Endothelial Function Endothelial function is also favorably affected by omega-3 fatty acids because the vasodilatory effect of nitrous oxide is enhanced by EPA. Treating humans with fish oil has been shown to decrease oxygen-derived free radical production in neutrophils.6 It has been suggested that this reduction in free radicals increases the bioavailability of nitrous oxide. Studies7 using ultrasonic tracking of brachial artery flow-mediated vasodilation have demonstrated improved large artery endothelium-dependent dilation in patients treated with fish oil. Endothelial function can also be improved by reducing the endothelial expression of vascular cell adhesion molecules, thus resulting in a reduction in leukocyte binding to the endothelium.8

Inhibition of Atherosclerotic Plaque Formation Ingestion of EPA and DHA also has been shown in animal studies to inhibit atherosclerotic plaque

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Pre-treatment with omega-3 fatty acids also markedly reduces postprandial lipemia, which typically occurs after consumption of a fatty meal, and postprandial lipoproteins are atherogenic. Postprandial lipemia is also thrombogenic because it increases levels of activated factor VII, a procoagulant. Ingesting olive oil results in the same degree of increase in factor VII as ingesting butter, whereas consuming fish oil prevents this postprandial increase.11 Omega-3 fatty acids have been shown to result in a favorable change in highdensity lipoprotein (HDL) cholesterol metabolism. It seems that omega-3 fatty acids cause an increase in the large cholesterol-rich HDL2 subtype while decreasing the smaller triglycerol-enriched HDL3 subtype;12,13 HDL2 is considered to be the most antiatherogenic HDL subtype. Evidence from clinical trials In the past three years, at least three major metaanalyses of omega-3 fatty acids and their relationship to cardiovascular morbidity and mortality were published14-16 which concluded that fish oils supplementation is associated with a decrease of the risk of cardiovascular events and cardiovascular disease death rates. In terms of cardiovascular efficacy and safety of omega-3 fatty acids, there are three most important clinical studies: The Diet and Reinfarction Trial (DART) study, the Gruppo Italiano per lo Studio della Sopravivenza nell´Infarto Miocardico (GISSI) Prevenzione and GISSI-HF trials and the Japan EPA Lipid Intervention Study (JELIS) study.


Original Study DART Study

Recommendations

In the DART, 2033 men after myocardial infarction were followed for two years. These were randomly assigned to a group instructed to increase fish intake to achieve daily consumption of EPA and DHA of approximately 900 mg or to a control group that received no specific information. The intervention group experienced 29% reduction in all-cause mortality and the incidence of reinfarction was reduced by 32%.17

Guidelines of various expert societies including American Heart Association,23 American Diabetes Association24 as well as the joint guidelines on cardiovascular prevention of nine European societies25 are in conformity with most meta-analyses and reports from well-conducted clinical trials. They concur that the evidence is particularly well-proven in secondary prevention and (although less robust) it is reliable in primary prevention setting, too.

Japan EPA Lipid Intervention Study18

For the primary prevention of cardiovascular events it is currently recommended to maintain the daily intake of DHA and EPA in the range of 300-600 mg. In secondary prevention higher dose of 900-1,200 mg a day is well-supported by the evidence. For the reasons of triglyceride lowering even higher dose between 3,000 and 4,000 mg of DHA and EPA is suggested.

The second study that usually belongs to the core evidence in any meta-analysis is the JELIS. It was a very large trial following 18,645 patients with hyperlipidemia (>3,500 of which had a history of a vascular event). The study subjects were randomly assigned to either statin alone or a combination of statin and 1.8 g of EPA daily. After five years, the combination treatment was associated with a significant reduction of the primary composite endpoint comprising death, revascularization, myocardial infarction and unstable angina by 19% compared to the statin alone group. A post-hoc analysis of the secondary prevention subgroup revealed similar benefit of the statin + EPA combination of cardiovascular outcomes in this subgroup in which relative risk was reduced by 23%.19 The greatest relative risk reduction of 53% in primary prevention was experienced in patients with increased triglyceride and decreased HDL cholesterol levels.20

GISSI-Prevenzione Study21 The third study providing a substantial part of the data in the meta-analyses is the GISSI-Prevenzione study. Eleven thousand three hundred twenty-three survivors of myocardial infarction were randomized to 850 mg of DHA/EPA daily or usual care. Treatment significantly reduced risk of death from any cause by 28% after only four months, being driven mainly by the lowering of sudden cardiac death risk by 45%. The differences remained significant for the whole 3.5-year duration of the study. Effects of omega-3 fatty acids were studied by the same group in a population of heart failure patients.22 Three thousand four hundred ninety-four patients with heart failure were randomized to 850 mg of omega-3 fatty acids daily and 3,481 received matching placebo. DHA/EPA administration reduced the risk of death from any cause by 9% (p = 0.041) and hospitalization for cardiovascular reasons by 8% (p = 0,009), which means 56 patients needed to be treated for 3.9 years to prevent one death.

The recommended intake of omega-3 fatty acids can be achieved by increased oily fish consumption; however, for the purpose of triglyceride lowering dietary supplements of concentrated EPA/DHA are usually necessary. A standardized capsulated concentrate of EPA and DHA as a prescription drug is also available in the USA and some European countries.26 Future directions In the future, the recommendation is that the dose should be according to the actual need of a particular patient based on the measurement of plasma concentration of omega-3 fatty acids. As reviewed by Albert and co-workers concentrations of omega-3 fatty acids in plasma are strong predictors of sudden cardiac death.27 Therefore, Harris has proposed a new marker of cardiovascular risk - an omega-3 index.28 This index reflects the proportion of omega-3 fatty acids in the membrane of red blood cells. Omega-3 index exceeding 8% is associated with the lowest risk of cardiovascular events while levels <4% are typically found in coronary artery disease patients.29 Thus, omega-3 index may help identify those who would benefit most from omega-3 fatty acids supplementation. Conclusions Therapy with low-dose omega-3 fatty acids significantly reduces the incidence of sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease.1 Results of individual clinical trials as well as meta-analyses of omega-3 fatty acids impact on cardiovascular outcomes provide enough evidence to encourage intake of

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Original Study EPA/DHA daily in primary and secondary prevention of cardiovascular disease, respectively.30 The target EPA + DHA consumption should be at least 500 mg/day for individuals without underlying overt cardiovascular disease and at least 800-1,000 mg/day for individuals with known coronary heart disease and heart failure. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA omega3 polyunsatured fatty acid that provides maximal cardioprotection in those at risk of cardiovascular disease as well in the treatment of atherosclerotic, arrhythmic and primary myocardial disorders.31 In the future, more personalized recommendation based on assessment of individual omega-3 fatty acids needs (using e.g. omega-3 red blood cell index) would be possible.

12. Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ. Dietary fish as a major component of a weightloss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. Am J Clin Nutr 1999;70(5):817-25.

References

16. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, et al. n-3 Fatty acids from fish or fishoil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006;84(1):5-17.

1.

Covington MB. Omega-3 fatty acids. Am Fam Physician 2004;70(1):133-40.

2.

Leaf A, Kang JX, Xiao Y, Billman GE. n-3 fatty acids in the prevention of cardiac arrhythmias. Lipids 1999;34 Suppl: S187-9.

3.

Connor SL, Connor WE. Are fish oils beneficial in the prevention and treatment of coronary artery disease? Am J Clin Nutr 1997;66(4 Suppl):1020S-1031S.

4.

Goodnight SH Jr, Harris WS, Connor WE. The effects of dietary omega 3 fatty acids on platelet composition and function in man: a prospective, controlled study. Blood 1981;58(5):880-5.

5.

Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999;70(3 Suppl):560S-569S.

6.

Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 2000;35(2):265-70.

7.

Vogel RA, Corretti MC, Plotnick GD. The postprandial effect of components of the Mediterranean diet on endothelial function. J Am Coll Cardiol 2000;36(5): 1455-60.

8.

De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr 2000;71(1 Suppl):213S-23S.

9.

Fox PL, DiCorleto PE. Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein. Science 1988;241(4864):453-6.

10. Nestel PJ. Fish oil and cardiovascular disease: lipids and arterial function. Am J Clin Nutr 2000;71(1 Suppl): 228S-31S. 11. Harris WS, Connor WE, Alam N, Illingworth DR. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res 1988;29(11):1451-60.

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13. Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD, Beilin LJ. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 2000;71(5):1085-94. 14. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ 2006;332(7544):752-60. 15. Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 2008;83(3):324-32.

17. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989;2(8666):757-61. 18. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al; Japan EPA Lipid Intervention Study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369(9567):1090-8. 19. Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, et al; JELIS Investigators. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J 2009;73(7):1283-90. 20. Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, et al; JELIS Investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 2008;200(1):135-40. 21. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354(9177):447-55. 22. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al; Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372(9645):1223-30.


Original Study 23. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association Nutrition Committee: Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2003;107:2747-57.

27. Albert CM, Campos H, Stampfer MJ, Ridker PM, Manson JE, Willett WC, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002;346(15):1113-8.

24. Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R; American Heart Association; American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation 2007;115(1):114-26.

28. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk 1997;4(5-6):385-91.

25. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R; ESC Committee for Practice Guidelines. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Atherosclerosis 2007;194(1):1-45. 26. Brunton S, Collins N. Differentiating prescription omega3-acid ethyl esters (P-OM3) from dietary-supplement omega-3 fatty acids. Curr Med Res Opin 2007;23(5): 1139-45.

29. Block RC, Harris WS, Reid KJ, Sands SA, Spertus JA. EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls. Atherosclerosis 2008;197(2):821-8. 30. Vrablík M, Prusíková M, Snejdrlová M, Zlatohlávek L. Omega-3 fatty acids and cardiovascular disease risk: do we understand the relationship? Physiol Res 2009;58 Suppl 1:S19-26. 31. Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 2009;54(7):585-94.

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Clinical Study

Hypocholesterolemic Effects of Lactobacillus acidophilus as A Dietary Supplement M Vani*, M Shiva Prakash**, P Yashoda Devi*

Abstract To study the effect of supplementation of Lactobacillus acidophilus on lipid profile in individuals with hypercholesterolemia. We selected 30 hypercholesterolemia subjects (15 men and 15 women) with ages ranging between 42-53 years old; the intervention was performed for a period of 60 days. During the intervention all 30 subjects were divided into three groups comprising of 10 individuals in each group. Group A and B were given 10 × 106 and 20 × 106 viable L. acidophilus organisms and Group C served as a nonsupplemented group, however, they were on medication to lower the cholesterol levels. Fasting blood samples were drawn initially at 0, 30 and after 60 days of supplementation and analyzed for lipid profile which included total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol. All the recruited subjects were completed the study. Comparisons of lipid profile were made at different time periods i.e., 0, 30 and after 60 days of treatment. The supplementation with either 10 × 106 or 20 × 106 viable L. acidophilus led to significant reduction in cholesterol, triglycerides and increase of HDL cholesterol levels. The supplementation of L. acidophilus is found to have a beneficial effect on the lipid profile in hypercholesterolemic subjects. Keywords: Lactobacillus acidophilus, cholesterol, triglycerides, dietary supplements

O

ne of the major modifiable risk factor for coronary heart disease mortality is elevated plasma cholesterol concentration.1 Data from epidemiological and nutritional studies indicate that high concentration of total serum cholesterol and low-density lipoprotein (LDL) cholesterol correlate to the incidence of coronary heart disease.2 Hypercholesterolemia has been implicated to be the primary and important causative factor in underlying coronary heart disease.3 The increase in the incidence may be due to high intakes of saturated fat, or animal fat, one of the major dietary factors for causation of hypercholesterolemia.4 Other associated factors were found to be smoking hypertension, diabetes mellitus, sedentary lifestyles, excess weight and stress.5 It has been shown that higher levels of cholesterol are associated the prevalence of ischemic heart disease in both women and men.6 A reduction in high serum cholesterol levels can reduce the risk of coronary heart disease.

*Dept. of Food and Nutrition Acharya NG Ranga Agricultural University, Rajendra Nagar, Hyderabad **National Institute of Nutrition (ICMR), Hyderabad Address for correspondence Dr M Shiva Prakash Assistant Director (Scientist-D) National Institute of Nutrition (ICMR) Jamai-Osmania, Tarnaka, Hyderabad - 500 007

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It was demonstrated that healthy people having cholesterol levels within the normal range had a reduction in the risk of future cardiovascular events.7 Further, it was suggested that the rate of coronary events is reduced by raising high-density lipoprotein (HDL) cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.8 Hence, there is an urgent need to develop intervention programs for the treatment of hypercholesterolemia through dietary modifications, weight reduction and drugs. Drugs used to treat hypercholesterolemia include cholestyramine resin, cholesterol hydrochloride, niacin, gemfibrozil, probucol and statin which, work by different mechanisms in reducing the serum cholesterol concentration.9-11 However, these are associated with side effects which include gastrointestinal discomfort and impaired systematic absorption. Dietary management is the cornerstone in the management of high blood cholesterol concentration. Several findings have shown that low fat vegetarian diet or a diet high in cereal fiber, fruits and vegetables can reduce the risk of hypertension, dyslipidemia and cardiovascular disease.12,13 There is a necessity for a dietary rather than a drug approach keeping in mind, the side effects which are associated with the use of drugs. A number of studies on probiotics


Clinical Study have demonstrated the beneficial effects on human health especially in controlling the lipid profile.14,15 Therefore, the present study was taken upto see the effect of a commercially and locally available strain of Lactobacillus acidophilus. L. acidophilus which belongs to the genus. L. acidophilus is a homo-fermentative species, fermenting sugars into lactic acid. Generally, L. acidophilus strains are considered to have probiotic characteristics. These strains are commercially used in many dairy products, sometimes together with S. thermophilus and Lactobacillus delbrueckii in the production of acidophilus-type yogurt and a typical Indian ‘dahi‘ (curd). Some strains of L. acidophilus have been studied extensively for health effects and found to be effective in decreasing pediatric diarrhea, intestinal bowel syndrome, toxic amines and lactoseintolerance by helping lactose digestion.16 The serum hypocholesterolemic effect of probiotic bacteria such as L. acidophilus has attracted much interest in medical research recently.17,18 Few studies have shown that some strains of Lactobacillus could lower cholesterol content.19,20 For the past several decades, there has been increasing interest in understanding the mechanisms of cholesterol reduction by probiotics, but very recently one study reported that the gene ccpA, which encodes catabolite control protein A, plays an important role in cholesterol reduction by probiotic bacteria.21 Some strains of L. acidophilus were found to secrete bile salt hydrolase which catalyzed the hydrolysis of glycine- or taurine-conjugated bile salts into amino acid residues and free bile salts.22 Another mechanism suggested for cholesterol reduction is that L. acidophilus incorporates some of the cholesterol into cellular membranes, and that results in cholesterol being less available for the absorption from the intestine into the blood.23 Most of the studies for cholesterol reduction in serum by using L. acidophilus and other strains were carried out with rats as an experimental animals, but this study was investigated in human volunteers. Material and Methods

Bacterial Cultures L. acidophilus (strain no. UBLA-34) was obtained from Unique Biotech Limited, Hyderabad, Andhra Pradesh, India. The strain L. acidophilus UBLA-34 was finally made to

10 × 106 CFU/g and 20 × 106 CFU/g. The L. acidophilus was supplemented as powder form.

Subjects Thirty hypercholesterolemia subjects were selected from the Endocrinology Research Centres of Hyderabad city, Andhra Pradesh, India. The age group ranged between 42-53 years (15 males and 15 females). Subjects with serum cholesterol levels of >200 mg/dl i.e., 200-240 mg/dl were included in the study. The L. acidophilus strain no. UBLA-34 obtained from Unique Biotech Limited located at Hyderabad was used for supplementation. The Institutional Ethical Committee approval was obtained before the commencement of the study. The subjects were explained about the risk of hypercholesterolemia and the beneficial role of the supplement L. acidophilus and informed consent was obtained before the commencement of the study. The subjects were advised not to take high cholesterol diet i.e., fried foods, butter, ghee, egg yolk, etc. During the experimental period they were advised to avoid smoking, consumption of alcohol but to continue their habitual diet along with L. acidophilus as a supplement to their diet. The subjects were advised to take L. acidophilus at two dosage level i.e., 10 × 106 (Group A) and 20 × 106 (Group B) viable organisms along with their diet. A structured schedule was used to record their habitual dietary pattern, physical activity, smoking and drinking habits, etc.

Laboratory Investigations Blood samples were collected for lipid profile analysis at 0, 30 and 60 days. Total cholesterol was estimated by enzymatic method of Liebermann.24 Triglycerides were estimated using glycerol phosphate oxidase (GPO) method of Fossati and Lorenzo.25 HDL was estimated by enzymatic method of Demacker and Hifman.26 Results The physical examination and initial blood sample reports showed that all the subjects were healthy without signs of liver disease, renal disease and diabetes (Table 1). The results from Table 2 reveal that in groups A and B, for 30 days, the serum total cholesterol levels were significantly decreased with supplementation with L. acidophilus these values further decreased significantly in both the groups at the and of 60 days

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Clinical Study Table 1. Characteristics of the Subjects Studied Particulars

Female (n = 15)

Male (n = 15)

Total

%

No.

%

No.

%

42-47 years

7

46.7

6

40.0

13

43.3

48-53 years

8

53.3

9

60.0

17

56.7

Age

Discussion

Education Upto 10th

6

40.0

3

20.0

9

30.0

10-12th

8

53.3

4

26.7

12

40.0

Graduation

1

6.7

6

40.0

7

23.3

Post graduation

0

0

2

13.3

2

6.7

House wife

13

86.7

0

0

13

43.3

Service

1

6.7

8

23.3

9

30.0

Business

1

6.7

7

46.7

8

26.7

Occupation

Per capita income/ month (Rs.) 3,000-4,000

11

73.3

12

80.0

23

76.7

>4,000

4

26.7

3

20.0

7

23.3

Vegetarian

8

53.3

6

40.0

14

46.7

Nonvegetarian

6

40.0

9

60.0

15

50.0

Ovo-vegetarian

1

6.7

0

0

1

3.3

Nonalcoholic, nonsmoking

15

100.0

1

6.7

16

53.3

Nonalcoholic, smoking

0

0

1

6.7

1

3.3

Nonsmoking, alcoholic

0

0

8

53.3

8

26.7

Alcoholic, smoking

0

0

5

33.3

5

16.7

25-30

13

86.7

14

93.3

27

90.0

30-31

2

13.3

1

6.7

3

10.0

Habitual diet

Other habits

BMI (kg/m2)

(p < 0.001). This decrease in trend was found to be similar to that of Group C i.e., subjects that were on medication with cholesterol lowering drugs. The triglyceride levels were also significantly lowered in Group A and B at 30 and 60 days supplementation which was on par with the results of medication group.

310

Table 3 and with respect to HDL cholesterol, in Group A the levels were significantly increased only after 60 days of supplementation (p < 0.001) whereas in Group B with 20 Ă— 106 L. acidophilus supplementation it was found that there was a significant increase even after 30 days and as well as 60 days (Table 4).

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The present data suggest that serum cholesterol and triglycerides decreased significantly with a significant increase in HDL cholesterol. The reason for the hypocholesterolemic effect of L. acidophilus might be due to inhibition of 3-hydroxy, 3-methyl glutaryl CoA reductase, which is a rate limiting enzyme in endogenous cholesterol biosynthesis in the body and also by deconjugation of bile acids in the intestine which is an important mechanism in reducing the cholesterol concentrations.27 Increased deconjugation of bile acids could also result in the greater excretion of bile salts from the intestinal tract which stimulates the synthesis of replacement of bile salts from intestinal tract which stimulates synthesis of replacement of bile acids from cholesterol, thus providing the potential to reduce the cholesterol levels in the body.28 The effect of Lactobacilli on triglycerides could be due to the action of lipase from the Lactobacilli, which breaks the larger molecular fats into simple and easily digestible substrates i.e., fatty acids and glycerol.29 The effect of Lactobacillus on LDL, VLDL and HDL cholesterol was unsettled in the present study. Earlier, it was reported that a probiotic mixture of L. acidophilus and Streptococcus faecalis decreased the synthesis of cholesterol in the liver and increased the loss of steroids in rats.30 Further, it was suggested that L. acidophilus can enhance the reduction of serum cholesterol in rats that had been fed a high cholesterol diet, probably through alteration in the enterohepatic circulation of bile acids.31 The present results indicate that the observed hypocholesterolemic effect is some how dependent on the presence of the bacteria in the product. An increase in HDL cholesterol may be due to fermentation of the microflora. An ability of certain strains of lactobacilli to assimilate cholesterol in the presence of


Clinical Study Table 2. Total Cholesterol Levels of Hypercholesterolemia Subjects before and after L. acidophilus Supplementation for Different Groups at Different Time Periods Category

Dosage of L. acidophilus supplemented 106

viable organisms/ day/individual

Serum cholesterol levels (mg/dl); Mean values ± SD (n = 10) 0 day 228.1a

± 6.4

After 30 days 214.1b

± 6.0

After 60 days 203.5c

F value

Level of significance

± 9.6

89.42

p < 0.001

Group A

10 x

Group B

20 x 106 viable organisms/ day/individual

229a ± 7.7

208.1b ± 8.9

197.5c ± 5.6

487.03

p < 0.001

Group C

Nil

233.5a ± 12.8

208.7b ± 14.5

197.9c ± 12.7

217.89

p < 0.001

(on medication) NB: Difference in the superscript indicate statistical significance at different time points at p < 0.001.

Table 3. Triglyceride Levels of Hypercholesterolemia Subjects before and after L. acidophilus Supplementation for Different Groups at Different Time Periods Category

Dosage of L. acidophilus supplementation

Triglyceride levels (mg/dl); Mean values ± SD (n = 10) 0 day

After 30 days

After 60 days

F value

Level of significance

Group A

10 x 106 viable organisms/ day/individual

251.9a ± 36.1

245.5b ± 36.6

241.2c ± 36.1

165.16

p < 0.001

Group B

20 x 106 viable organisms/ day/individual

282.6a ± 43.6

275.5b ± 43.4

268.6c ± 43.6

193.61

p < 0.001

Group C

Nil

287.6a ± 59.2

271a ± 82.4

263.3c ± 80.0

56.57

p < 0.001

(on medication) NB: Difference in the superscript indicate statistical significance at different time points at p < 0.001.

Table 4. HDL Cholesterol Levels of Hypercholesterolemia Subjects before and after L. acidophilus Supplementation for Different Groups at Different Time Periods Category

Dosage of L. acidophilus supplementation 106

viable organisms/ day/individual

HDL cholesterol levels (mg/dl); Mean values ± SD (n = 10) 0 day 41.3a

± 2.2

After 30 days 42.2a,b

± 1.9

After 60 days 42.6c.b

F value

Level of significance

± 1.7

8.40

p < 0.01

Group A

10 x

Group B

20 x 106 viable organisms/ day/individual

41.6a ± 2.2

42.3b ± 2.5

43.1c ± 1.9

12.62

p < 0.001

Group C

Nil

40.8a ± 1.8

41.8b ± 2.16

42b ± 1.7

9.59

p < 0.001

(on medication) NB: Difference in the superscript indicate statistical significance at different time points at p < 0.001.

bile acids has been demonstrated and suggests a possible association between gut microflora and cholesterol absorption.32 The viability of fermenting bacteria strain in the human gut and ultimately the ability to colonise the small intestine where most of the absorption of cholesterol takes place, could be expected to be important for the effect.

Conclusions From this study it can be concluded that supplementation with 20 × 106 L. acidophilus viable organisms/day/individual for a period of 60 days is more effective and beneficial in bringing out remarkable changes in serum lipid profile than 10 × 106 viable organisms/day/ individual for the same functional parameters. This study

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Clinical Study demonstrate the beneficial effects of supplementation of L. acidophilus as a food supplement to control the abnormal lipid levels of the hypercholesterolemic subjects. This supplementation with Lactobacillus along with physical exercise may prove beneficial in reducing the incidence of coronary heart diseases. Further studies are needed to determine the optimal dosing of L. acidophilus as supplementation for cardiovascular protection.

Acknowledgments We convey our thanks to Dr (Mrs) M Ratna Sudha, Managing Director of M/S Unique Biotech Limited, Hyderabad, Andhra Pradesh, India for providing us the L. acidophilus (strain no. UBLA-34) which was given as supplement in this study.

REFERENCES 1.

Shipley MJ, Pocock SJ, Marmot MG. Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study. BMJ 1991;303(6794):89-92.

2.

Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiology and causation of coronary heart disease and stroke in India. Heart 2008;94(1):16-26.

3.

Singh RB, Rastogi V, Niaz MA, Ghosh S, Sy RG, Janus ED. Serum cholesterol and coronary artery disease in populations with low cholesterol levels: the Indian paradox. Int J Cardiol 1998;65(1):81-90.

4.

Ockene IS, Nicolosi R. Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 1998;338(13):917; author reply 918-9.

5.

Verschuren WM, Jacobs DR, Bloemberg BP, Kromhout D, Menotti A, et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study. JAMA 1995;274(2):131-6.

6.

Lindblad U, Langer RD, Wingard DL, Thomas RG, Barrett-Connor EL. Metabolic syndrome and ischemic heart disease in elderly men and women. Am J Epidemiol 2001;153(5):481-9.

7.

Chow C, Cardona M, Raju PK, Iyengar S, Sukumar A, Raju R, et al. Cardiovascular disease and risk factors among 345 adults in rural India - the Andhra Pradesh Rural Health Initiative. Int J Cardiol 2007;116(2):180-5.

8.

9.

Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279(20):1615-22. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs

High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341(6):410-8. 10. Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med 2006;99(3):257-73. 11. Florentin M, Liberopoulos EN, Elisaf MS. Ezetimibeassociated adverse effects: what the clinician needs to know. Int J Clin Pract 2008;62(1):88-96. 12. Anderson JW, Hanna T. Impact of nondigestible carbohydrates on serum lipoproteins and risk for cardiovascular disease. J Nutr 1999;129(7 Suppl): 1457S-66S. 13. Mozaffarian D, Kumanyika SK, Lemaitre RN, Olson JL, Burke GL, Siscovick DS. Cereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals. JAMA 2003;289(13):1659-66. 14. Gilliland SE, Nelson CR, Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol 1985;49(2):377-81. 15. Klaver FA, van der Meer R. The assumed assimilation of cholesterol by Lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl Environ Microbiol 1993;59(4):1120-4. 16. Sanders ME, Klaenhammer TR. Invited review: the scientific basis of Lactobacillus acidophilus NCFM functionality as a probiotic. J Dairy Sci 2001;84(2):319-31. 17. Park YH, Kim JG, Shin YW, Kim SH, Whang KY. Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J Microbiol Biotechnol 2007;17(4):655-62. 18. Mathara JM, Schillinger U, Guigas C, Franz C, Kutima PM, Mbugua SK, et al. Functional characteristics of Lactobacillus spp. from traditional Maasai fermented milk products in Kenya. Int J Food Microbiol 2008;126 (1-2):57-64. 19. Adebawo OO, Banjoko Y, Osilesi T. Evaluation of the hypocholesterolemic effect of Lactobacillus acidophilus fermented maize meal (ogi) in rats. The FASEB Journal 2008;22:1092.7 20. Sridevi N, Vishwe P, Prabhune A. Hypocholesteremic effect of bile salt hydrolase from Lactobacillus buchneri ATCC 4005. Food Res Int 2009;42:516-20. 21. Lee J, Kim Y, Yun HS, Kim JG, Sejong OH, Kim SH. Genetic and proteomic analysis of factors affecting serum cholesterol reduction by Lactobacillus acidophilus A4. Appl Env Micro 2010:4829-35. 22. Corzo G, Gilliland SE. Measurement of bile salt hydrolase activity from Lactobacillus acidophilus based on disappearance of conjugated bile salts. J Dairy Sci 1999;82(3):466-71. 23. Noh DO, Kim SH, Gilliland SE. Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121. J Dairy Sci 1997;80(12):3107-13. Cont’d on page 316...

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case report

Common Coronary Trunk from the Right Sinus of Valsalva Giving Origin to Right and Left Coronary Arteries MONIKA MAHESHWARI*, CHANDRA PRAKASH TANWAR**

Abstract We report herein an interesting case of a rare coronary anomaly of a common coronary trunk presenting with angina. Keywords: Coronary anomaly, angina, coronary angiography

C

oronary artery anomalies are rare entities. Overall incidence is 0.3-1.3% of patients undergoing coronary angiography1 and 0.17% of routine autopsy studies.2 The most commonly occurring congenital anomaly of coronary vessels, is the left circumflex artery originating from the right coronary artery. Other anomalies include - origin of left coronary artery from pulmonary artery, origin of right coronary artery from left sinus of Valsalva, presence of a single coronary artery, hypoplastic coronary vessels, coronary artery aneurysms and coronary artery fistula. We report here an interesting case report of single coronary trunk from the right sinus of Valsalva giving origin to right and left coronary arteries.

clubbing, icterus or lymphadenopathy. Jugular venous pressure (JVP) was normal. Chest skiagram showed mild cardiomegaly. Electrocardiogram (ECG) revealed shallow ‘T’ wave inversion in precordial leads (V1-V6). Cardiac enzymes levels were within normal limits. 2D-echocardiogram showed normal left ventricular functions with some apical hypertrophy. A treadmill exercise test was planned to evaluate inducible ischemia and functional capacity but the test was prematurely terminated at stage-2 because of exhaustion and dyspnea. Diagnostic coronary angiography was therefore undertaken, which revealed an anomalous coronary anatomy, with the origin of right coronary artery and left main stem from the right sinus of

CASE REPORT A 52-year-old male presented in emergency department with retrosternal chest pain since two months, which was pressure-like in nature sometimes precipitated by effort but often occurred at rest. On physical examination, her blood pressure was 140/90 mmHg, pulse 82/minute, respiratory rate 16/minute and temperature 98.4°F. There was no pallor, cyanosis,

*DM (Cardio) 2nd Year Resident Dept. of Cardiology **MD (Gn Medicine) 2nd Year Resident Dept. of Medicine Jawaharlal Nehru Medical College, Ajmer Address for correspondence Dr Monika Maheshwari Navin Niwas, 434/10, Bapu Nagar Ajmer, Rajasthan - 305 001 E-mail: opm11@rediffmail.com

RCA

LAD

LCX LMCA

Figure 1. Coronary angiogram (in left anterior oblique projection) showing origin of right coronary artery and left main stem from the right sinus of Valsalva as a common coronary trunk.

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case report Valsalva as a common coronary trunk (Fig. 1). The coronary arteries were free of atherosclerotic disease.

blood supply to the myocardium is integral for proper surgical revasularization in presence of coronary artery disease.

DISCUSSION Lipton et al classified the coronary artery system as L when the single coronary artery originated from the left sinus of Valsalva and R when it originated from the right sinus of Valsalva.3 An aberrant origin of the main stem from the right sinus of Valsalva represents one of the rarest forms of all coronary anomalies, seen in only 0.0024-0.044% of the population. In such cases with a common arterial trunk nourishing the entire heart, the main stem takes one of 4 aberrant pathways to reach its proper vascular territory. These pathways are designated as type A (anterior to the right ventricular outflow tract), type B (between the aorta and pulmonary trunk), type C (cristal, coursing through the crista supraventricularis portion of the septum), and type D (dorsal or posterior to the aorta).4-6 These may be responsible for ischemia, congestive heart failure and sudden death. All angiographers and cardiac surgeons need to be familiar with these anatomic variants because accurate identification and delineation of the course and distribution of coronary vessels with nature of

REFERENCES 1.

Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Cathet Cardiovasc Diagn 1990;2(1):28-40.

2.

Alexander RW, Griffith GC. Anomalies of the coronary arteries and their clinical significance. Circulation 1956;14(5):800-5.

3.

Lipton MJ, Barry WH, Obrez I, Silverman JF, Wexler L. Isolated single coronary artery diagnosis, angiographic classification and clinical significance. Radiology 1979;130(1):39-47.

4.

Leberthson RR, Dinsmore RE, Bharati S, Rubenstein JJ, Caulfield J, Wheeler EO, et al. Aberrant coronary artery origin from the aorta. Diagnosis and clinical significance. Circulation 1974;50(4):774-9.

5.

Desmet W, Vanhaecke J, Vrolix M, Van de Werf F, Piessens J, Willems J, et al. Isolated single coronary artery: a review of 50,000 consecutive angiographies. Eur Heart J 1992;13(12):1637-40.

6.

Mohan JC, Tomar D, Shekar C, Mohan V, Kaur B. Single coronary artery supplying the entire heart. Indian Heart J 2011;63:280.

...Cont’d from page 312 24. Liebermann LL. A method for the estimation of serum cholesterol. Clinical Chem 1958;2:26-30. 25. Fossati P, Lorenzo P. Serum triglycerides determined calorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28(10):2077-80. 26. Demacker PN, Hijmans AG, Vos-Janssen HE, van’t Laar A, Jansen AP. A study of the use of polyethylene glycol in estimating cholesterol in high-density lipoprotein. Clin Chem 1980;26(13):1775-9. 27. Bongaerts GP, Severijnen RS, Tangerman A, Verrips A, Tolboom JJ. Bile acid deconjugation by Lactobacilli and its effects in patients with a short small bowel. J Gastroenterol 2000;35(11):801-4. 28. Walker DK, Gilliland SE. Relationship among bile tolerance, bile salt deconjugation, and assimilation of cholesterol by Lactobacillus acidophilus. J Dairy Sci 1993;76(4):956-61.

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29. el-Sawah MM, Sherief AA, Bayoumy SM. Enzymatic properties of lipase and characteristics production by Lactobacillus delbrueckii subsp. bulgaricus. Antonie Van Leeuwenhoek 1995;67(4):357-62. 30. Fukushima M, Nakano M. Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on cholesterol metabolism in rats fed on a fat- and cholesterol-enriched diet. Br J Nutr 1996;76(6):857-67. 31. Kiessling G, Schneider J, Jahreis G. Long-term consumption of fermented dairy products over 6 months increases HDL cholesterol. Eur J Clin Nutr 2002;56(9):843-9. 32. Mohan JC, Arora R, Khalilullah M. Preliminary observations on effect of Lactobacillus sporogenes on serum lipid levels in hypercholesterolemic patients. Indian J Med Res 1990;92:431-2.


medilaw

Insight on Medicolegal Issues Can a Cardiologist Complaint Against Another Cardiologist for his Unethical Practices

For almost a decade, residents have been limited to work shifts of no 30 hours, with a maximum of 80 hours in a given week.

Ans: In fact, Medical Council of India (MCI) encourages a doctor to expose unethical conducts of other doctors. In the recent case of Medical Council of India Vs Indian Medical Association (IMA) where MCI took action against the President and Secretary of IMA for violation of code of conduct for endorsing a product, it was on the behest of a doctor’s complaint against the association to MCI.

But studies continue to document the problems among residents who repeatedly work 24-hour shifts, such as having twice the incidence of episodes of inattention during the night and performing 1.5-2 standard deviations below resting performance on clinical and nonclinical activities.

MCI Act (1.7): “Exposure of Unethical Conduct: A Physician should expose, without fear or favor, incompetent or corrupt, dishonest or unethical conduct on the part of members of the profession.”

The commission recommended these evidence-based actions that healthcare organizations can initiate to alleviate the hazards associated with caregiver fatigue: 

Can the hospital be liable for residents mistake if the mistake happens due to over work?

JCAHO: Risk Seen with Sleepy Docs

Despite efforts to limit working hours among healthcare providers, fatigue continues to pose hazards to staff and patients alike, according to a sentinel event alert from the Joint Commission.

Among the evidence cited in the report were findings that when residents work recurrent 24-hour shifts, there were 36% more adverse events than when they work for only 16 hours at a time, and they made five times the number of important diagnostic mistakes. That distinction is especially noteworthy in light of the new work hour restrictions implemented last July limiting first year residents to work shifts no longer than 16 hours without a sleep break.

Examine the shift structures and staffing levels of the organization to identify potential risks Focus on procedures during the hand-off process, when mistakes can easily be made by tired staff Consider staff input in organizing schedules and encourage participants to raise concerns about fatigue Encourage the use of specific strategies for combating fatigue, including physical activity, participating in active conversations, and avoidance of caffeine before bed Implement measures involving teamwork for particularly critical staff tasks and patients with complicated conditions Provide education about sleep hygiene and reinforce the importance of adequate sleep for patient safety Look for evidence of fatigue when reviewing adverse events In settings where staff are granted sleep breaks, ensure that an appropriate environment is provided.

“Shift length and work schedules have a significant effect on healthcare providers’ quantity and quality of sleep and, consequently, on their job performance, as well as on the safety of their patients and their individual safety,” the commission stated.

“We have a culture of working long hours,” said Christopher P Landrigan, MD, who directs a program on sleep and patient safety at Brigham and Women’s Hospital in Boston.

Fatigue can have numerous undesirable effects, including lapses in attention and memory, difficulties in communicating and problem solving, and impairments in understanding and judgment.

Education will be needed to change this culture and to ensure that healthcare workers are aware of their limitations and the importance of circadian influences on job performance, according to Landrigan.

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expert’s opinion

Is there an Association between Hypertension and Depression? J Nagpal, KK Aggarwal

D

epression may not be a major risk factor in the development of coronary heart disease (CHD) but has been proposed as a likely risk factor for hypertension (HT) and CHD. Depression has recently been found to predict recurrence of and mortality due to myocardial infarction (MI) in a series of studies1,2 and HT incidence in a prospective population-based study.3 The relation between depression and HT is biologically plausible given the increased adrenergic activity in depression4-6 that may have a pressor effect on the cardiovascular system.5 However, several crosssectional and prospective studies 7-10 could not establish any relation between depression and HT.

References

To determine, if depressive symptoms independently predict HT incidence, a prospective, multicenter, epidemiological was undertaken in a cohort of young adults (aged 23-35 years at study entry) from the general community without hypertension and followed up for five years.11 A sample of 3,343 adults from four urban areas stratified for race (black and white) from the CARDIA (Coronary Artery Risk Development in Young Adults) study. The main outcome measure was hypertension incidence, which was defined as blood pressure >160/95 mmHg (assessed on a single occasion) or the use of prescribed antihypertensive medication. The investigators came to the conclusion that depressive symptoms were predictive of later hypertension incidence in young adults, and young blacks with depressive symptoms were at high-risk of developing hypertension. The 2008 American Heart Association scientific advisory on Depression and Coronary Heart Disease recommends screening for depressive symptoms in all cardiovascular disease patients.12 All patients should be evaluated by the Patients Health Questionnaire (PHQ-2) for screening by asking the question, over the past two weeks, how often have you been bothered by any of the following problems: Little interest or pleasure in doing things and or feeling down, depressed or hopeless.

1.

Frasure-Smith N, et al. The impact of negative emotions on prognosis following myocardial infarction: is it more than depression? Health Psychol 1995;14(5):388-98.

2.

Carney RM, et al. Major depressive disorder predicts cardiac events in patients with coronary artery disease. Psychosom Med 1988;50(6):627-33.

3.

Jonas BS, et al. Are symptoms of anxiety and depression risk factors for hypertension? Longitudinal evidence from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Arch Fam Med 1997;6(1):43-9.

4.

Siever LJ, et al. Overview: toward a dysregulation hypothesis of depression. Am J Psychiatry 1985;142(9):1017-31.

5.

Yeragani VK. Heart rate and blood pressure variability: implications for psychiatric research. Neuropsychobiology 1995;32(4):182-91.

6.

Musselman DL, et al. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998;55(7):580-92.

7.

Goldberg EL, et al. Psychosocial factors and blood pressure. Psychol Med 1980;10(2):243-55.

8.

Jones-Webb R, et al. Relationships between depressive symptoms, anxiety, alcohol consumption, and blood pressure: results from the CARDIA Study. Coronary Artery Risk Development in Young Adults Study. Alcohol Clin Exp Res 1996;20(3):420-7.

9.

Simonsick EM, et al. Depressive symptomatology and hypertension-associated morbidity and mortality in older adults. Psychosom Med 1995;57(5):427-35.

10. Davidson K, et al. Anxiety, hostility, anger expression, and blood pressure in a population-based sample: the NSHS Study. Ann Behav Med 1998;20(Suppl):S78. 11. Davidson K, et al. Do depression symptoms predict early hypertension incidence in young adults in the CARDIA study? Arch Intern Med 2000;160(10):1495-500.

A ‘yes’ answer to either part should prompt the doctor to look for depression.13

12. Lichtman JH, et al. AHA Science Advisory. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation 2008;118(17):1768-75.

Source: 50 Questions in Hypertension, Volume 5, 2010.

13. Kroenke K, et al. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16(9):606-13.

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practice guidelines

ACCP Releases Statement on Dyspnea Treatment in Patients with Advanced Lung or Heart Disease More than 90 percent of patients with advanced chronic obstructive pulmonary disease and more than 60 percent with advanced heart disease experience breathlessness. Approximately 94 percent of patients with chronic lung disease experience dyspnea in the last year of life. One study found that many patients who died of chronic obstructive pulmonary disease had dyspnea, with serious dyspnea more common than serious pain. Although it is not known what causes dyspnea, physicians should provide treatment for this symptom. Patients have not received consistent or effective treatment for dyspnea; therefore, the American College of Chest Physicians (ACCP) wrote a consensus statement to influence clinical practice and provide suggestions regarding the management of dyspnea in patients with advanced lung or heart disease. Measurement Physicians are ethically obligated to treat dyspnea. They should routinely ask patients about the intensity of their breathlessness, which should then be documented in the medical record. Physicians should also reassure patients and their families that they will treat dyspnea. Evaluation of dyspnea should include asking about the distress, meaning, and needs that come with breathlessness. Three instruments are available to measure dyspnea: the Borg scale, visual analog scale, and numerical rating scale. Currently, there is no reason to use one instrument over another. Physicians should start treatment with the understanding that they should reassess whether the treatment is improving dyspnea without causing adverse effects. Treatment

Nonpharmacologic Oxygen therapy is the standard of care for patients with hypoxemia, but only a limited number of studies have assessed the short-term effects of supplemental oxygen

Source: Adapted from Am Fam Physician. 2010;82(8):999-1000.

on breathlessness at rest in patients with advanced lung disease. Two studies found significant improvements in dyspnea with oxygen therapy, whereas two found no benefit. No randomized controlled trials have evaluated the effect of oxygen therapy in patients with advanced heart disease. The ACCP determined that supplemental oxygen can provide relief for patients with dyspnea who are hypoxemic at rest or during minimal activity. No studies were found that evaluated the effect of supplemental oxygen in patients without hypoxemia at rest. Pursed-lip breathing, a breathing strategy often used by patients with airway obstruction, can provide relief of dyspnea. When performed at rest, pursed-lip breathing improves oxygen saturation, reduces carbon dioxide levels, and promotes slower, deeper breathing. Relaxation therapy can also relieve dyspnea. One study found that, compared with patients who sat quietly, those who listened to a recorded relaxation message reported less dyspnea. Another study found that progressive muscle relaxation reduced dyspnea in patients with chronic obstructive pulmonary disease after each of four weekly sessions, but not at the end of the four-week period. Noninvasive positive pressure ventilation can provide some relief. Three systematic reviews of noninvasive positive pressure ventilation concluded that it improved the patient’s perception of dyspnea. Four other studies found modest to significant improvement of dyspnea, as reported by the patient.

Pharmacologic Oral and parenteral opioids can improve dyspnea. One review of 13 studies of persons with a variety of advanced chronic diseases found that morphine was effective for treating dyspnea. Two reviews of palliative care determined that short-term opioid therapy is effective for treating dyspnea at the end of life. Dosing and titration considerations should include renal, hepatic, and pulmonary function, and current and past opioid use. Respiratory depression and overdose are concerns with the use of opioids. One study found that higher doses of opioids used in the withdrawal of life-sustaining

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practice guidelines treatment were not associated with decreased time from withdrawal of life support to death. Other studies determined that survival time was not related to the dosage of morphine. Only one of 11 studies on arterial blood gases or oxygen saturation reported significant changes in oxygenation with opioids. Arterial carbon dioxide partial pressure did increase with the use of opioids; however, it did not exceed 40 mm Hg. Opioids may cause other adverse effects, including constipation, confusion, drowsiness, hallucinations, nausea or vomiting, and psychosis. Ethical Issues Treatment of dyspnea should not be limited by concerns about addiction or dependence. The principle of double effect is a rationale for using opioids or sedatives that may hasten death, assuming the reason for increasing

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the dose is to provide relief from dyspnea. Physicians should assess patients for anxiety and depression, which often accompany dyspnea. Physicians should communicate with patients about end-of-life care. Although it has been shown that most patients with advanced disease want to discuss end-of-life care with their physicians, few physicians discuss such issues with their patients. It is important to understand the barriers to this communication. In some cultures, family members may have different views regarding the role of family and who should be involved in decision making about treatment at the end of life. Differences in family perspectives or spiritual beliefs on the value of maintaining consciousness at the end of life, as well as the value of suffering, should be anticipated. Physicians should be prepared to apply principles of culturally effective end-of-life care in these situations.


Revisiting 2011

Top Cardiology News of 2011 1.

ARISTOTLE trial: New oral factor Xa inhibitor apixaban is better than warfarin in atrial fibrillation (AF) patients.

2.

According to British scientists, it may be possible for the heart to repair itself after injury, and they have discovered a protein molecule that seems to stimulate this process. (Dr Peter Weissberg, medical director of the British Heart Foundation). The cells that are capable of this healing are already there in the epicardium.

3.

Cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib raised high-density lipoprotein (HDL) cholesterol levels without increasing blood pressure and without impairing endothelial function (dalVESSEL trial).

4.

The Food and Drug Administration (FDA) is recommending that physicians restrict prescribing high-dose simvastatin to patients, given an increased risk of muscle damage. The new FDA drug safety communication, states that physicians should limit using the 80 mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.

5.

Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug. The new label has warnings not to use the drug with various medications, including itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine and danazol. The 10 mg dose should not be exceeded in patients taking amiodarone, verapamil and diltiazem; the 20 mg dose should not be exceeded with amlodipine and ranolazine.

6.

New reports of two elderly women faring badly when taking the novel anticoagulant dabigatran for stroke prevention in AF have prompted more discussion about the caution needed with this drug when treating the very old or those with renal impairment. 7. Sanofi-Aventis has sent US healthcare professionals a letter warning them about cases of rare but severe hepatic injury associated with use of the antiarrhythmic drug dronedarone. The FDA has also issued a ‘safety communication’. 8. A new Cochrane review has provoked controversy by concluding that there is not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease. (Dr Fiona Taylor, London School of Hygiene and Tropical Medicine, UK). 9. New data help shed light on the malpractice risk physicians face in clinical practice. Cardiologists have a higher-than-average risk of being sued, but these lawsuits are less likely to result in a financial payment to plaintiffs. The surgical specialties face the largest threat of litigation, with approximately 20% of neurosurgeons and cardiothoracic surgeons facing a malpractice claim each year. Pediatricians and psychiatrists had the lowest risk of being sued. (Dr Amitabh Chandra, Harvard University, Boston). 10. Arrhythmia-free survival rates after a single catheter-ablation procedure are relatively low at five years, just 29%, but the long-term success increases to 63% when outcomes are measured after the last ablation procedure. (Dr Rukshen Weerasooriya Hôpital Cardiologique du HautLévêque, Bordeaux-Pessac, France).

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lighter reading

One day the king and his friend were out on a hunting expedition. The friend would load and prepare the guns for the king. The friend had apparently done something wrong in preparing one of the guns, for after taking the gun from his friend, the king fired it and his thumb was blown off. Examining the situation the friend remarked as usual, ‘This is good!’ To which the king replied, ‘No, this is NOT good!’ and proceeded to send his friend to jail. About a year later, the king was hunting in an area that he should have known to stay clear of. Cannibals captured him and took them to their village. They tied his hands, stacked some wood, set up a stake and bound him to the stake. As they came near to set fire to the wood, they noticed that the king was missing a thumb. Being superstitious, they never ate anyone that was less than whole. So untying the king, they sent him on his way. As he returned home, he was reminded of the event that had taken his thumb and felt remorse for his treatment of his friend. He went immediately to the jail to speak with his friend. ‘You were right,’ he said, “it was good that my thumb was blown off.” And he proceeded to tell the friend all that had just happened. “And so I am very sorry for sending you to jail for so long. It was bad for me to do this.” ‘No,’ his friend replied, ‘This is good!’ “What do you mean, ‘This is good’? How could it be good that I sent my friend to jail for a year?” “If I had NOT been in jail, I would have been with you.” Situations may not always seem pleasant while we are in them, but the promise of God is clear. If we love Him and live our lives according to His precepts, even that which seems to be bleak and hopeless will be turned by God for His glory and our benefit. Hold on, God is faithful! May God bless you this week as you seek His will in every situation. −Ms. Ritu Sinha

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−Dr GM Singh

Classroom Psychology – Final Exam

Laugh a While

The story is told of a king in Africa who had a close friend with whom he grew up. The friend had a habit of looking at every situation that ever occurred in his life (positive or negative) and remarking, ‘This is good!’

“God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference. Serenity Prayer.”

A psychology professor at the University of Miami knew his students expected a terrifyingly long final exam. To play with their minds a little (what do you expect from a psychology professor?) he only put ONE question on the final exam. He watched the reactions of the students as they all opened the exams and saw the one question. Initially, they all looked relieved, but as the difficulty of the question began to sink in, those relieved faces sagged to confusion and consternation. All, that is, except for one student. He read the question, tapped his pencil into his palm a few times, then jotted something down on the test paper. He walked upto the professor, handed him the final, and walked out. The professor blinked in surprise, looked at what the student wrote, and smiled. The professor wrote ‘100%’ on the top of that student’s test. The Question: What is courage? The Student’s Answer: This is. −Dr GM Singh

Make Sure

During Medical Practice

A patient of suspected MI died after receiving sublingual nitrate.

Oh my God! Why was a history of intake of Viagra drug not taken?

©IJCP Academy

This is Good!

Quote

An Inspirational Story

Lighter Side of Medicine

Make sure to take a history of Viagra drug intake before giving nitrates, because the two drugs coadministered can cause a fatal fall in blood pressure. KK Aggarwal




Asian

Journal of

CLINICAL CARDIOLOGY

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). Asian Journal of Clinical Cardiology 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.

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.

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

-

Confidence intervals for the measurements should be provided wherever appropriate.

Results These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

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Discussion -

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g. practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles

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.)_______________________________

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.

2. Total number of pages ________________________

Books

6. Suggestions for reviewers (name and postal address)

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1._ _______________

2.____________

2._ _______________

Articles in Books

3.____________

3._ _______________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

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. -

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

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3. Number of tables ____________________________ 4. Number of figures ___________________________ 5. Special requests _____________________________

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 Asian Journal of Clinical Cardiology E - 219, Greater Kailash, Part - 1, New Delhi - 110 048. Phone: 011-40587513 E-mail: editorial@ijcp.com, emedinew@gmail.com Website: www.ijcpgroup.com




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