Statistical tools for analysing the data obtained from repeated dose toxicity studies with rodents: A comparison of the statistical tools used in Japan with that of used in other countries.

In the present study, an attempt was made to compare the statistical tools used for analysing the data of repeated dose toxicity studies with rodents conducted in 45 countries, with that of Japan. The study revealed that there was no congruence among the countries in the use of statistical tools for analysing the data obtained from the above studies. For example, to analyse the data obtained from repeated dose toxicity studies with rodents, Scheffé’s multiple range and Dunnett type (joint type Dunnett) tests are commonly used in Japan, but in other countries use of these statistical tools is not so common. However, statistical techniques used for testing the above data for homogeneity of variance and inter-group comparisons do not differ much between Japan and other countries. In Japan, the data are generally not tested for normality and the same is true with the most of the countries investigated. In the present investigation, out of 127 studies examined, data of only 6 studies were analysed for both homogeneity of variance and normal distribution. For examining homogeneity of variance, we propose Levene’s test, since the commonly used Bartlett’s test may show heterogeneity in variance in all the groups, if a slight heterogeneity in variance is seen any one of the groups. We suggest the data may be examined for both homogeneity of variance and normal distribution. For the data of the groups that do not show heterogeneity of variance, to find the significant difference among the groups, we recommend Dunnett’s test, and for those show heterogeneity of variance, we recommend Steel’s test.

Clinical and biochemical parameters in relation to serum leptin levels in south indian children and adolescents.

Objective. To investigate the relationship between serum leptin and lipid profile in South Indian School children and adolescents, and to evaluate the role of serum leptin in obese, overweight and congenital heart diseased children and adolescents; in South Indian population and its correlation with anthropometric and biochemical parameters. Methods. The study included 185 school going children and adolescents. (52 obese, 49 overweight, 25 congenital heart disease children and adolescents, were compared with 59 normal controls, aged between 10-17 years). Anthropometric variables, lipid profile, fasting serum glucose were analyzed by autoanalyser and serum leptin by ELISA. Results. Serum leptin levels were significantly elevated in obese and overweight children than in control children (36.88±18.60ng/mL, 20.64±11.18ng/mL vs 7.97±2.79ng/mL; p value <0.001), and decreased in congenital heart diseased children than in control children (6.20±4.23 ng/mL vs 7.97±2.79ng/mL; p value <0.005). Conclusions. This study provides a good relationship between serum leptin levels and anthropometric and biochemical parameters, such as total cholesterol, triglycerides and LDL-cholesterol. We observed negative correlation between serum leptin and fasting glucose levels and HDL-cholesterol levels were found to be non-significant among the groups. Further studies with large sample size are needed to ascertain the relationship between serum leptin and lipid profile in different groups of children and adolescents.

Multiple cardiovascular involvement in a case of relapsing polychondritis.

Relapsing polychondritis is a multisystem disease characterized by recurrent inflammation of the cartilaginous tissue. Cardiovascular manifestations of relapsing polychondritis are rare but are the second most common cause of death in these patients. We report a case of relapsing polychondritis who underwent aortic valve replacement uneventfully but presented six months later with myocardial infarction due to bilateral coronary ostial stenosis.

Thrombolysis with percutaneous transluminal balloon angioplasty of a blocked modified Blalock-Taussig shunt.

Transcatheter balloon recanalization of occluded Blalock-Taussig shunts in the early post-operative period has been reported in the past but there are issues regarding the role of thrombolysis in this situation. We present our experience with such a procedure in an infant with blocked modified Blalock-Taussig shunt.

Homograft valve bank: our experience in valve banking.

BACKGROUND: A cardiac homograft valve bank with cryopreservation facility was established at the Institute of Cardiovascular Diseases, Madras Medical Mission, Chennai in July 1995. METHODS AND RESULTS: During the last 7 1/2 years of its existence, from July 1995 to March 2003, 588 hearts were processed. The valves harvested were 390 aortic, 400 pulmonary and 39 others including mitral valve, aortic conduits, pericardium etc.; 176 (29.9%) hearts were discarded for various reasons which included failure to sterilize, HBV, HIV, HCV, treponema pallidum hemagglutination test positivity, atheromatous/fatty streaks, incompetent valves, and dissection mistakes. The valves were sterilized using an antibiotic cocktail of vancomycin, amikacin, streptomycin, cefotaxime and amphotericin B in Hank's balanced salt solution. Of the 585 valves issued for clinical use, 247 were aortic, 323 pulmonary and 15 others (mitral valve, pericardium, conduits). Gram negative bacilli were the predominant contaminants from the hearts during the first half (July 1995 to February 1999) and gram positive organisms were the predominant contaminants during the later half (March 1999 to March 2003) of the study period. A variety of fungal contaminants like candida, aspergillus, penicillium and other fungi were also isolated from the homograft hearts at procurement. The valves were used most commonly for Rastelli procedure/right ventricular-pulmonary artery conduit (48.71%) followed by Ross procedure (23.41%). The other procedures were aortic valve replacement (6.15%), truncus repair (5.81%), unifocalization with conduit repair (6.49%), aortoplasty (0.512%), left ventricular-pulmonary artery conduit (0.512%), pulmonary valve replacement (0.512%), aneurysm repair (0.34%), Norwood repair (0.34%), mitral valve replacement (0.17%) and other procedures (7%). CONCLUSIONS: We have established a viable and functioning cardiac homograft valve bank to suit Indian conditions and till date, have issued 585 homograft valves for clinical use.

Nocardia asteroides mediastinitis complicating coronary artery bypass surgery.

A 63 years diabetic male was admitted with mediatinitis and sternal dehiscence. Nocardia asteroides sensu stricto Type VI was isolated from the mediastinal tissue and fluid during debridement. Prompt surgical intervention and treatment with ofloxacin both intravenously and later orally led to the cure.

Hydatid cyst of the left ventricle of the heart.

Hydatid disease of the heart is rare. We report a case of hydatid cyst of left ventricle in a forty year old lady where the diagnosis was made intra-operatively. The transthoracic and transesophageal echocardiography showed a mixed echogenic mass arising from the left ventricle. The diagnosis of hydatid cyst was confirmed by the demonstration of scolex and hooklets in the cyst fluid. Hydatid cyst should be a differential diagnosis for a mixed echogenic mass on echocardiography.

Heart-lung transplantation in India: initial experience.

Heart-lung transplantation is a well accepted and standard form of therapy for the surgical management of patients with end-stage cardiopulmonary disorders. The first heart-lung transplant in India was performed at our institution on May 3, 1999 and, subsequently, 2 more patients have undergone this procedure. The initial experience is encouraging and heralds a new era of thoracic organ transplantation in India.

Temporary endoepicardial atrioventricular sequential pacing for complete heart block following complex surgery for congenital heart disease.

Complete heart block following intracardiac surgical repair for complex congenital heart disease is not uncommon. In the presence of ventricular dysfunction, ventricular pacing alone may not improve the cardiac output. We report the feasibility and efficacy of endoepicardial atrioventricular sequential pacing in a case of postoperative complete heart block.

HLA expression in aortic and pulmonary homografts: effects of cryopreservation.

BACKGROUND: The present study was undertaken to find out the HLA allo-antigens on cardiac homografts. METHODS AND RESULTS: One pulmonary and eight aortic homografts were studied for the presence of major HLA class I and class II antigen expression. Cadaveric hearts were procured from the mortuary and kept in Hank's balanced salt solution with antibiotics at 4 degrees C. Bits were taken from the conduits and valves every 24 hours for 14 days during storage and snap-frozen using liquid nitrogen. A total of 1368 sections were made using a cryostat. These sections were stained using 4 monoclonal antibodies: BLA class I (MO736), class II HLA-DR (MO746), CD45 (MO701), and endothelial stain (MO616). All monoclonals were procured from DAKO. Class I antigen molecules could be demonstrated on the endothelial surface of the vessel wall from day 1 to day 4 to 5 of storage. They stained weaker and could not be demonstrated after day 10 of storage. Class I antigen molecules were positive in very fresh valves and by day 5-6 could not be seen on the valve surface. Class II (HLA-DR) antigen expression was present in the subendothelial layer from day 1 to day 12-14 of storage. They could also be demonstrated in valves and conduits released after cryopreservation. These class II staining cells were also stained by CD45 monoclonal antibody and hence could be macrophages, histiocytes or leucocytes. The endothelium was very well demonstrated in the vessel walls from day 1 to day 12-14 of storage; it could only be seen in very fresh valves. Storage in the liquid medium and sterilization procedures led to loss of endothelial lining of the valves. After cryopreservation and thawing, class I antigen molecules could not be demonstrated on the valves and conduits. Class II antigen molecules and CD45-stained cells continued to be demonstrated in the subendothelial layer and the valve matrix. The endothelium was intact in the vessel wall after cryopreservation and thawing, but could not be seen in the released valves. CONCLUSIONS: Allograft aortic and pulmonary conduits and valves are immunogenic, and HLA-ABC and HLA-DR antigen molecules can be demonstrated on different components of the vessel wall and valve leafets.

Extrinsic obstruction of the main coronary arteries in a child with hypertrophic cardiomyopathy.

Phasic narrowing of the coronary arteries on angiography is a well-known entity in both children and adults and has been described in relation to all epicardial arteries. There is a high incidence of myocardial bridges in hypertrophic cardiomyopathy. We report the case of a 6-year-old girl with hypertrophic obstructive cardiomyopathy who had extrinsic obstruction of the left main and right coronary arteries.

Ross procedure in an infant.

The Ross procedure is gaining acceptance as the procedure of choice for aortic valve replacement in children. We present the case of a 4-month-old child (weight 3.2 kg) suffering from congenital valvar aortic stenosis who underwent a Ross procedure. We believe that this is the youngest patient to have undergone this procedure successfully in the Indian subcontinent.

Batista procedure as a bridge to cardiac transplantation.

A 37-year-old male patient with dilated cardiomyopathy and end-stage heart failure underwent Batista procedure. After 6 months, he underwent orthotopic heart transplantation. Though he did not survive the procedure, we conclude that Batista procedure may serve as a cost-effective biological bridge to cardiac transplantation.

Electrophysiological studies with repeated episodes of ischaemia on isolated rat heart.

In order to know the beneficial effect of preconditioning electrocardiography recording were used as tool to assess myocardial malfunction and for this perfusion apparatus was setup. Electrophysiological changes for each heart were recorded during perfusion at 1, 2, 3, 5, 10, 20, 30 and 60 min of global ischaemia and also during the equal period of reperfusion. Recordings dembnstrate that the normal rate was about 240 beats/min with an "R" amplitude of 4mV. During the first ischaemic episode of 1min the rate was 180 +/- 15 beats/min (counted as per 'R' wave deflection), at 2 mins it was 60 +/- 6 beats/min, at 3 min the rate was 40 +/- 2 beats/min, at 5 mins of ischaemia it was 90 +/- 6 beats/min, at 10 min 20 +/- 2 beats/min, at 20 min the rate was 60 +/- 4 beats/min, and at 30 mins there were nil beats/min. The recovery during all the periods of reperfusion was restored to between 120 and 180 beats/min in all episodes. Further after a 60 min of ischaemia the heart stopped to elicit any mechanical response. It is concluded that short term ischaemia can induce a resilient effect on the beating of the heart after a few episodes as seen subsequent to 1 and 2 min of ischaemia. Further, preconditioning was beneficial up to 30 min, beyond which the heart showed signs of fatigue and irreversible injury.

Cryopreservation of cardiac homografts.

A homograft valve bank for cryopreservation of cardiac homografts was established at the Institute of Cardiovascular Diseases in July 1995. From July 1995 to February 1999, 169 donor hearts were processed. All except four hearts were procured post mortem. Aortic valves (149) and pulmonary valves (139) were the common homografts dissected out for use. The valves were immersed in a cocktail of five broad spectrum antibiotics and antifungals for an average of 48 to 72 hours before cryopreservation. Fifty-three (35.57%) aortic and 42 (30.21%) pulmonary valves had to be discarded for various reasons like fungal contamination, failure to sterilise, HBsAg positivity etc.; 153 homografts have been released for use so far. Analysing the usual methods of procurement, sterilisation protocol, culture and cryopreservation used for cardiac homografts at this centre, this paper recommends observance of timeliness, use of appropriate media for preservation of heart parts, administration of specific drugs and safeguards necessary for cryopreservation procedure.

Role of inhaled nitric oxide as a selective pulmonary vasodilator in pediatric cardiac surgical practice.

Our aim was to assess the role of inhaled nitric oxide (NO) therapy in post operative cases of congenital heart defects who developed pulmonary arterial hypertensive (PAH) crisis and had no response with conventional management. From February '95 to January '97, inhaled NO therapy was used in 21 children. Age ranged from 2 months to 9 years (mean 5.6 years) and duration of therapy ranged from 1 to 13 days. Of 21 patients, 17 responded well with 5-20 ppm while 4 did not. The preoperative mean pulmonary systolic pressure was 88 mm Hg against mean systemic pressure of 96 mm Hg. Post operatively, their PA pressure reduced to 62 mm Hg, with systemic pressure of 98 mm Hg. After using inhaled NO, PA pressure dropped to 24 mm Hg (mean systolic) (p < 0.007), after excluding the non responders. Of 4 non responders, two died due to irreversible pulmonary vascular disease and remaining two died due to residual defects. The study shows that inhaled NO is a selective pulmonary vasodilator, which is useful in postoperative PAH crisis and also reduces the transpulmonary gradient in single ventricle repair cases. It is safe and effective for prolonged use. It is very useful in Indian perspective, when more number of cases with congenital heart defects (CHD) along with severe PAH are encountered routinely.