Unusual dendritic keratitis.

Bilateral pseudo-dendritic keratitis in infancy can be due to tyrosinemia, a rare metabolic disorder. Ocular involvement may be the earliest presenting manifestation of this disease. Early diagnosis is essential because dietary modifications can result in complete reversal of the manifestations of this disorder. This disease must be suspected in all cases of non-responsive dendritic keratitis in the pediatric age group, especially if it is associated with cutaneous lesions such as patmoplantar keratosis. Serum tyrosine levels must be done in these cases.

Apolipoprotein E polymorphism and coronary heart disease.

Apolipoprotein E is a constituent of various lipoproteins and plays an important role in the transport of cholesterol and other lipids among cells of various tissues. The gene is polymorphic with three alleles (epsilon2, epsilon3, and epsilon4) coding for isoforms E2, E3, and E4 and having different binding affinities for the apo E receptors. While the epsilon2 allele is associated with elevated triglyceride levels, epsilon4 allele is associated with increased cholesterol levels. Though several studies support the role of apo E polymorphism in CHD either directly or indirectly via its influence on lipid and lipoprotein levels, there are some studies, which show no association. With the increasing incidence of CHD among Indians, it becomes imperative to identify genetic markers that may predispose individuals to coronary events. It would be of importance to determine if apo E gene will become a usefuladjunct to assess cardiovascular risk profile when performing genetic studies in families.

Molecular diagnosis of cystic fibrosis in Indian patients--a preliminary report.

AIM: The aim of the study was to screen for the common deltaF508 mutation and the poly T polymorphism and to determine their frequency in the cystic fibrosis transmembrane conductance regulator (CFTR) gene among the suspected CF cases referred to our clinical care centre for sweat chloride tests. METHODOLOGY: Sweat and EDTA blood samples were obtained from 23 clinically suspected cystic fibrosis (CF) cases. Sweat was estimated by pilocarpine iontophoresis procedure. Poly T polymorphism was detected by the multiplex-PCR based on ARMSTM technique and deltaF508 mutation by PCR-mediated site-directed mutagenesis method. RESULTS: Five cases, mainly with respiratory abnormalities and followed by steatorrhea had elevated sweat chloride levels (> 60 mmol/l), three of them, each with nutritional, respiratory and pancreatic abnormalities were borderline (40-60 mmol/l) and the remaining 15 clinically suspected CF cases had normal sweat chloride levels (< 40 mmol/l). The 9T variant was frequently observed (75%) in cases with elevated sweat chloride, including those exhibiting borderline values; with no 5T variant. The 7T was the most common variant (77%) observed in the cases with normal sweat chloride, with only one 5T variant (33%). Of the five cases with high sweat chloride, four cases were homozygous for deltaF508, whereas one was heterozygous with borderline sweat chloride, thus showing an overall frequency of 56.25% in the CF chromosome. DeltaF508 was found to be present with the 9T variant in all the instances. CONCLUSION: The presence of the 9T variant along with elevated sweat chloride levels can be used to predict a high risk of the individual harboring the severe deltaF508 mutation. It would be advisable to test for to the deltaF508 mutation along with the sweat chloride estimation in all the critically suspected CF cases diagnose CF with a higher degree certainty.

Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a risk factor for coronary heart disease in the Indian population.

OBJECTIVE: The screening and therapeutic guidelines for the management of lipid abnormalities are reasonably well established. However, other risk factors like hyperhomocysteinemia (HCA) and single nucleotide polymorphisms involving the angiotensin converting enzyme (ACE) and angiotensinogen genes, various clotting factors etc., have yet to be established firmly as other causative factors of atherothrombotic disease. Our study was aimed at finding the relationship between HCA, folate, vitamins B12 levels, and mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes. METHODS: We studied 230 subjects, which included patients with angiographically documented coronary heart disease (CHD) (n=115) and controls (n=115) with no history of CHD. RESULTS: Elevated levels of plasma homocysteine, above 18 nmoles/ml, were detected in 19.13% and 18.26% of our patients and controls, respectively. Homocysteine was significantly correlated to Apo A1 (r=0.51, p < 0.05) and Apo B (r=0.49, p < 0.05). The heterozygous MTHFR mutation was found to be 54.5% (12/22) in our patients with HCA. Of these, 31.8% (7/22) were deficient for plasma folate. Heterozygosity for T833C mutation in the CBS gene was observed in 9.99% (2/22) of our patients with HCA. Both these patients were also deficient for plasma folate and vitamin B12. CONCLUSION: In our study, heterozygosity for the thermolabile MTHFR mutation was found to be associated with hyperhomocysteinemia (HCA). This genetic predisposition to HCA could be risk factor for CHD and can be correlated with vitamin supplementation. To the best of our knowledge this is the first report from India on plasma homocysteine levels and its genetic aspect in patients with CHD.

Renal involvement in multiple myeloma.

The present study is a retrospective chart analysis of 33 patients who satisfied the diagnostic criteria of multiple myeloma. Sixteen (49.5%) of these 33 patients developed renal failure at some point in time. The mean age +/- 1SD of patients who developed renal failure was 59.2 +/- 13 years (range 34-85 years). There were 12 males and 4 females. The precipitating factors for renal failure were dehydration (12.5%), hypercalcemia (62.5%) and use of non-steroidal antiinflammatory drugs (6.2%). Hypercalcemia was observed in 10 of the 16 patients who developed renal failure while it was seen in only 4 of the 17 cases who did not develop renal failure (relative risk 5.4). In 11 (68.7%) patients, the renal function improved with hydration, treatment of hypercalcemia and chemotherapy. The 1 and 3 year actuarial survival of patients with renal failure and multiple myeloma was 87% and 74% respectively.

Evidence for free-radical mediated injury during coronary artery bypass surgery.

Prolonged global ischemia followed by reperfusion during coronary artery bypass graft (CABG) surgery leads to a burst of oxygen free-radical generation and subsequent myocardial impairment. Blood samples were collected at different time periods from the right atrium of patients (n = 55) who underwent CABG surgery. Free-radical activity was measured by assays for thiobarbituric acid reactive species (TBARS), mainly malondialdehyde (MDA), at zero minute (before aortic cross-clamp), one minute and 10 minutes after declamping i.e. reperfusion. There was a significant increase (p < 0.001) in the level of MDA at one minute of reperfusion which continued to be elevated up to 10 minutes. This increase was significantly correlated with aortic cross-clamp time (r = 0.525, p < 0.05). The activity of CPK and CPK-MB was raised by two fold (p < 0.001) after release of the clamp. Plasma Troponin-T level was estimated in 10 patients during CABG surgery and a significant increase (p < 0.01) was observed at one minute as well as 10 minutes of reperfusion which correlated well (r = 0.81, p < 0.01) with the severity of ischemia. The concomitant rise in TBARS (marker of free-radical activity), CPK, CPK-MB and Troponin-T (indicators of myocardial damage) on reperfusion implies that there is free-radical mediated damage to the cardiac membrane during CABG surgery.

Dyslipidemia in patients with chronic renal failure and in renal transplant patients.

Indian studies on lipid profile abnormalities in chronic renal failure (CRF) have varied from no abnormalities at all to significant abnormality (hypertriglyceridemia and reduced HDL) as described in the Western literature. Moreover, there is no Indian study on the effect of renal transplantation on the abnormal lipid profile of CRF. The aim of our study was to determine the lipid profile of CRF patients on conservative treatment, end stage renal disease (ESRD) patients on maintenance hemodialysis (HD) treatment and renal transplant patients. We also looked at the effect of fish oil rich in polyunsaturated fatty acids (Max-EPA) on hypertriglyceridemia of CRF. The study included 4 groups; Gp I: control subjects (n = 9, age = 30 +/- 5 yrs), Gp II: CRF patients on conservative treatment (n = 9, age = 49 +/- 17 yrs), Gp III: ESRD patients on HD for at least 3 months (n = 19, age = 53 +/- 9 yrs), Gp IV: 3 months post-renal transplant patients (n = 9, age 31 +/- 11 yrs). The lipids and lipoproteins analysed include total cholesterol, HDL, LDL, triglycerides, Apo A1 and Apo B. It was observed that in Gp II patients triglycerides were significantly elevated (p < .05) and Apo A1/Apo B significantly abnormally lower (p < .001) compared to Gp I. In Gp IV patients, there was no significant difference in lipid profile compared to Gp I. With the use of Max-EPA in 5 patients with hypertriglyceridemia, there was a significant improvement in hypertriglyceridemia (p < .05). Our study suggests: 1) significant hypertriglyceridemia does develop in a majority of CRF patients. The abnormality probably improves with dialysis treatment and renal transplantation. 2) A lower Apo A1/Apo B ratio in CRF patients may account for higher risk of atherosclerosis. 3) Fish oil rich in polyunsaturated fatty acids improves hypertriglyceridemia of CRF.

Prophylactic theophylline infusion for prevention of apnea of prematurity.

To assess if there was any advantage in the prophylactic use of theophylline to prevent apnea in preterms, we treated 56 preterms (Group A) < 34 weeks gestation with theophylline infusion and compared these with 25 age and weight matched preterms (Group B) who received no therapy. Aminophylline (25 mg/ml) was infused from admission in all neonates (group A) at rates ranging 0.2 to 0.38 mg/kg/h and blood levels estimated on an Abbots TDX analyser by Fluorescence Polarization Immunoassay, after 5 days infusion. All neonates (Groups A + B) were monitored on a Corometric 505 neonatal monitor. In Group A, 1/48 developed primary apnea while in Group B, 4-21 had primary apnea (p < 0.05). Serum theophylline ranged from 2.3 to 39.5 micrograms/ml with a mean of 12.7 micrograms/ml. The mean serum level of theophylline in 4 cases who exhibited clinical evidences of toxicity was 30.1 micrograms/ml. A statistically significant difference (p < 0.05) was noted in birth weight and serum level inspite of similar infusion rates of theophylline. A linear correlation r = 0.65 was noted between serum level and infusion rate. Multivariate regression analysis, between birth weight and gestational age to serum level, showed a linear correlationship only between birth weight and serum level (r = 0.45).