Biomedical subjects
Publications and source records attributed to S Rajan.
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.
BACKGROUND: Genotypes of the drug-metabolizing enzyme CYP2D6 influence plasma levels of 25% of commonly prescribed drugs. This is the first study in India to investigate the genotype-phenotype relationship of CYP2D6. AIM: To study the influence of some CYP2D6 genotypes on the metabolism of its substrate dextromethorphan in healthy South Indian volunteers and to assess the contribution of the CYP2D6*10 and CYP2D6*4 alleles. MATERIALS AND METHODS: Twenty-six subjects from a previous CYP2D6 genotyping study of healthy volunteers were included for phenotyping in this study. Selected volunteers belonged to any one of three genotype groups:Group I - two normal activity alleles, Group II - one reduced activity allele and one normal activity allele and Group III - one loss of function allele along with either a wild type or reduced activity allele. Volunteers were phenotyped for the CYP2D6 enzyme using dextromethorphan as probe drug. Concentrations of the parent drug and metabolite dextrorphan were estimated using high performance liquid chromatography. Metabolic ratios were calculated as the ratio of parent drug to metabolite in 0-8h urine samples. STATISTICAL ANALYSIS: Metabolic ratios from each genotype group were compared using the Mann-Whitney test at 5% significance, to observe their difference between genotype groups. RESULTS: The mean metabolic ratios+/-SD in Groups I, II and III were 0.0039+/-0.0031, 0.0032+/-0.0017 and 0.0391+/-0.0331 respectively. The mean metabolic ratio of Group III was significantly higher when compared with Groups I or II. In heterozygous individuals, the *1 or *2 alleles compensated for the reduced enzyme activity due to the *10 allele. However, if a heterozygous individual had a *4 allele, the reduced enzyme activity could not be compensated by the *1 or *2 alleles. CONCLUSIONS: The CYP2D6 enzyme activity was found to be decreased in individuals carrying *4 or *5 alleles. The *1 or *2 allele could compensate for the reduced function due to *10 allele, but not for the loss of function due to *4 allele.
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A total of 12 cases underwent repair of complete atrioventricular (AV) septal defect utilising the two-patch technique. There were 4 males and 8 females. The mean age at repair was 9.6 months (range, 3 to 49 months). The average weight was 5.4 kg (range, 3.5 to 13 kg). Five had associated patent ductus arteriosus. A Gore-Tex patch and glutaraldehyde preserved pericardium was utilised for the ventricular and atrial portions of the defects respectively in all patients. Four of these were done under hypothermic circulatory arrest. There were no intra-operative deaths. Early mortality comprised of 2 patients (2/12, 16.6%). One due to a pulmonary hypertensive crisis and the other to septicemia. The mean duration of ventilatory support was 62 hours (range, 24 to 192 hours). The mean duration of inotropic support was 57 hours (range, 24 to 192 hours). Primary repair of AV septal defects using the two-path of technique can be accomplished with a low early mortality in carefully selected patients.
Eighteen patients under went surgical treatment of univentricular hearts between April 1989 till October 1992. All 18 had palliative operations in the form of: a modified Blalock-Taussig shunt (5), pulmonary artery banding (2), bidirectional Glenn shunts (2), conventional Fontan repair (1) and total cavo pulmonary connection (8). There were 11 males and 7 females. The mean age at operation was 4.5 years (range, 1 month to 24 years). The average weight at operation was 12.2 kg (range 2 to 43 kg). Associated anomalies included: transposition of the great arteries (4), pulmonary stenosis (9), pulmonary atresia (1), mitral atresia (1), atrioventricular septal defect (1) and patent ductus arteriosus (3). There were no intra operative deaths. There were 5 early deaths (27.7%). Causes of death were due to: blockage of a modified Blalock-Taussig shunt (1), respiratory failure (1), persistent ventricular arrhythmias (1) and low output syndrome (2). Treatment in the form of a systemic to pulmonary arterial shunt or an operation based on the Fontan principle may offer an initial palliative or definitive correction for this condition.
Presently total cavopulmonary connection is used as an alternative in complex congenital disorders requiring atriopulmonary connection. From January 1989 till November, 1992, a total of 18 cases underwent total cavopulmonary connection. There were 8 males and 10 females. The mean age at operation was 92 months (range 5 to 504 months). The average weight was 19.6 kg (range 5.25 to 42 kg). Diagnoses included: tricuspid atresia (6); univentricular heart (7); pulmonary atresia with intact interventricular septum (1); double outlet right ventricle, pulmonary stenosis with uncommitted ventricular septal defect (2); corrected transposition of the great arteries with multiple ventricular septal defects (1) and complete atrioventricular septal defect with double outlet right ventricle (1). The mean duration of ventilatory and inotropic support was 127 hours (range 12 to 528 hours) and 140 hours (range 24 to 528 hours) respectively. The average duration of hospital stay was 17.9 days (range 5 to 30 days). There was no intra-operative mortality. Early mortality was 22.2% (4/18). Pre-operative diagnoses of patients who died were: tricuspid atresia (1), univentricular heart (1), complete atrio-ventricular septal defect with double outlet right ventricle (1) and double outlet right ventricle, pulmonary stenosis with uncommitted ventricular septal defect (1). The causes of death were: low-output syndrome (3) and septicemia (1). Although these initial results with total cavopulmonary connection suggest a lower early mortality compared to other modifications of the Fontan principle, long-term follow-up would be necessary to assess the late implications of this procedure.