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Biomedical subjects

T A Chowdhury

Publications and source records attributed to T A Chowdhury.

At least 19 recordsLinked to original sources

Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes.

AIMS/HYPOTHESIS: Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. METHODS: We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). RESULTS: No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin '+' and '-' genotypes and alleles between the three diabetic cohorts. CONCLUSIONS/INTERPRETATION: Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom.

Adult

Comparison of secondary prevention measures after myocardial infarction in subjects with and without diabetes mellitus.

OBJECTIVES: To survey and compare secondary prevention measures in diabetic and non-diabetic patients following myocardial infarction (MI). DESIGN: Follow-up of a cohort of patients who suffered their first MI 1 year previously. SETTING: Three district general hospitals. MAIN OUTCOME MEASURES: Review 1 year post-MI for signs of left ventricular failure (LVF), serum cholesterol, smoking status, weight, blood pressure and glycaemic control. Assessment of appropriate treatment with aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering therapy before discharge and at least 1 year post-MI. RESULTS: A total of 189 non-diabetic and 86 diabetic patients were studied. Most patients received beta-blockers and aspirin appropriately, and most gave up smoking. In non-diabetic subjects, cholesterol fell significantly (P < 0.05), as did the proportion of patients with cholesterol > 5.5 mmol L(-1) (P < 0.05), whereas cholesterol did not fall significantly in diabetic subjects, due to a lower proportion of patients being on lipid-lowering therapy (27.5 vs. 37.9%). A higher proportion of non-diabetic patients with LVF were treated with ACE inhibitors compared with diabetic subjects (73.6 vs. 61.%). Glycaemic control did not improve in the diabetic subjects. CONCLUSIONS: Patients with diabetes do not receive optimal secondary prevention measures compared with their non-diabetic counterparts. This issue needs to be addressed by all units dealing with patients with diabetes in order to reduce the mortality and morbidity of MI in such patients.

Adrenergic beta-Antagonists

Genetic determinants of diabetic nephropathy.

Diabetic nephropathy is the most serious complication of diabetes mellitus. Progression of the condition leads to end-stage renal failure, and other complications of diabetes are also common in this group of patients. The onset of overt albuminuria in a patient with diabetes heralds an increased risk of death, particularly from cardiovascular disease. There is considerable evidence to show that nephropathy is influenced by genetic factors. Epidemiological studies show that only a minority of patients with diabetes develop nephropathy irrespective of glycaemic control, suggesting that a subgroup of patients are at higher risk of nephropathy. Marked ethnic variation is observed, with nephropathy being more common in certain ethnic groups. Familial clustering of nephropathy is also observed. Parental history of hypertension, diabetes or cardiovascular disease appears to predispose to nephropathy in patients with diabetes. A number of methods are available to dissect polygenic disease: animal models, genetic association studies (case-control studies), affected sib-pair studies, discordant sib-pair studies and transmission distortion analysis. Most published work has been based on association studies. Association studies have shown conflicting results often due to small numbers of cases and controls, and poor phenotypic characterization. The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism has been studied in detail, but does not appear to be a strong risk marker for nephropathy. It does, however, appear to have a role in response to angiotensin-converting enzyme inhibition, with II homozygotes being the most responsive and DD homozygotes the least. A number of other genetic loci have also shown positive associations with nephropathy, including apolipoprotein E, heparan sulphate and aldose reductase. More recently, affected sib-pair analysis and discordant sib-pair analysis have suggested possible genetic loci on chromosomes 3, 7, 9, 12 and 20. These have yet to be reproduced in larger numbers of families, and the specific gene regions on these chromosomes remain elusive. The evidence presented in this review strongly supports the role of genetic factors in nephropathy. Detection of strong genetic risk markers for nephropathy will allow further insights into the pathogenesis of nephropathy, and possibly the development of novel therapeutic agents for its treatment. It will also allow preventive therapy to be directed at those patients with the greatest risk for development of diabetic nephropathy.

Animals

Glomerular filtration rate determination in diabetic patients using iohexol clearance--comparison of single and multiple plasma sampling methods.

Use of iohexol clearance has been described as the gold standard for the measurement of glomerular filtration rate (GFR). It is suggested that multiple plasma sampling following iohexol injection is required to accurately determine GFR by area under plasma clearance curve. The aim of this study was to determine whether single plasma sampling 4 h after injection of iohexol could accurately determine GFR in diabetic patients with mild to moderate renal failure, compared to multiple plasma sampling. A total of 120 GFR determinations in 36 patients with non-insulin dependent diabetic renal disease were done over 1 year. No acute deterioration was seen in renal function following injection of contrast in any patient. Strong correlation in GFR measurement was observed between the multiple plasma sampling method and the single plasma sampling method (r2 = 0.975). Single plasma sampling 4 h after bolus injection of iohexol is a safe and accurate method of determining GFR and change in GFR in diabetic subjects with mild to moderate renal impairment.

Diabetes Mellitus, Type 2

Clinical, biochemical and immunological characteristics of relapsers and non-relapsers of thyrotoxicosis treated with anti-thyroid drugs.

OBJECTIVES: This study aims to correlate clinical, biochemical and immunological factors seen at diagnosis of thyrotoxicosis with subsequent relapse within 5 years. DESIGN: Retrospective review of case notes, and biochemical assessment at least 5 years after cessation of treatment. SETTING: A large general hospital endocrine clinic. SUBJECTS: Patients presenting with a first episode of thyrotoxicosis between 1988 and 1991 who were treated with antithyroid drugs for at least 18 months. Main outcome measures. Relapse was determined by examination of hospital records, general practice records, patient questionnaire and thyroid function tests. RESULTS: A total of 216 subjects presented for the first time with thyrotoxicosis, of whom 89 (41.2%) suffered a relapse of the disease. On univariate analysis, clinical factors associated with increased relapse include younger age at diagnosis, goitre, marked tachycardia, requirement for higher maintenance dose of carbimazole, higher FT4 levels at diagnosis and smoking. Factors not predictive of relapse include presence of thyroid eye signs, positive family history, atrial fibrillation or congestive cardiac failure, acropachy or pretibial myxoedema, and presence or absence of thyroid autoantibodies. Logistic regression analysis showed relapse was predominantly determined by an FT4 > 56.2 nmol L ', pulse rate > 110, presence of goitre and a positive smoking history (R2 = 0.36, P < 0.001). Presence of these four factors predicted relapse in 76 (85.4%) of the 89 patients who relapsed. CONCLUSIONS: Increased 'toxicity' of thyrotoxicosis, goitre and smoking are associated with relapse of thyrotoxicosis, and this may be helpful in determining which patients may be better managed with early ablative therapy.

Adult

Elevated glycated haemoglobin in non-diabetic patients is associated with an increased mortality in myocardial infarction.

Diabetes is associated with increased mortality following acute myocardial infarction compared to the general population. Elevated glycated haemoglobin (HbA1c) in diabetic patients is also associated with increased mortality following acute myocardial infarction, while mild elevation in HbA1c are associated with impaired glucose tolerance. The aim of this study was to determine the influence of HbA1c on outcome of acute myocardial infarction in 253 non-diabetic patients, 46 of whom died in one year. In univariate analysis, risk factors for death included smoking, glucose, cholesterol and HbA1c. In logistic regression analysis HbA1c was an independent risk factor for death. Over one-third of the fatality group had an HbA1c in the highest quartile, compared to one-fifth of the surviving group (p = 0.02). Elevated HbA1c is a risk marker for short-term mortality following acute myocardial infarction in non-diabetic subjects.

Aged

Effect of Norplant on liver function.

Combined pills have known adverse effects on liver function. Progesterone based contraceptives are thought to be safer in this regard. The effect of Norplant, a levonorgestrel contraceptive implant, on liver function was evaluated in 149 Bangladeshi women of reproductive age in this study. Liver function tests and ultrasonography of hepato-biliary system were done before and after the implantation. The patients were followed upto two years. There were non-significant transient rise of serum bilirubin and slight enlargement of liver during the first year. There was no significant change in the levels of AST, ALT, alkaline phosphatase, total protein, albumin-globulin ratio and prothrombin time. The results suggest that Norplant has no adverse effect on liver function.

Adolescent

Lack of association of angiotensin II type 1 receptor gene polymorphism with diabetic nephropathy in insulin-dependent diabetes mellitus.

Several observations suggest that inherited factors are influential in the development of nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). Genetic components of the renin angiotensin system are possible candidate genes. The aim of this study was to determine the role of the hypertension associated angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in susceptibility to nephropathy in IDDM. We examined 264 Caucasoid patients with IDDM and overt nephropathy (as defined by persistent proteinuria in the absence of other causes, hypertension and retinopathy), 136 IDDM patients with long duration of diabetes and no nephropathy (LDNN group), 200 recently diagnosed IDDM patients (Sporadic Diabetic group), and 212 non-diabetic subjects. The AT1R gene polymorphism was assessed using the polymerase chain reaction and restriction isotyping. Genotype frequencies did not differ significantly between the sporadic diabetic group and the nephropathy group (p = 0.245), nor between the long duration non-nephropathy group and the nephropathy group (p = 0.250). Allele frequencies were not significantly different between the three groups (p = 0.753). We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.

Adolescent

ApoE genotype and Alzheimer's disease in adults with Down syndrome: meta-analysis.

The apoE gene polymorphism was examined in 100 adults with Down syndrome (with and without dementia) compared to 346 control subjects without mental retardation. Meta-analysis of available data (480 subjects) revealed that apolipoprotein E genotype distribution for people with Down syndrome was similar to that of the nonretarded population. Although no significant association between possession of the apoE epsilon 4 allele and onset of Alzheimer's disease was found, subjects with the allele had a tendency towards lower age of onset of dementia. Subjects with apoE epsilon 2 allele may not develop dementia and may have increased longevity.

Adult

Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM.

Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.

Adult

Does empiric esophageal dilation benefit dysphagia when endoscopy is normal?

Some patients referred for esophagogastroduodenoscopy (EGD) to evaluate symptoms of dysphagia have normal endoscopies. How best to manage these patients is unclear. We reviewed our experience with empiric esophageal dilation in this setting. Over a five-year period, 40 consecutive patients with esophageal dysphagia and normal EGD underwent empiric esophageal dilation at the time of their endoscopy. Postdilation follow-up was available in 37 of the 40. The patients were divided into two groups depending on whether their dysphagia was to solid food only or to both solids and liquids. The two groups were comparable as regards age, sex, and the frequency of heartburn. Complete resolution of dysphagia was seen in 19 of 20 patients (95%) with solid-food-only dysphagia. In contrast, only two of 17 patients (12%) with solid and liquid dysphagia had complete resolution with empiric dilation, although another six patients (35%) had partial improvement. The difference in response between the two groups was highly significant (P < 0.0001). The response to dilation in patients with dysphagia to solid food only was often long-lasting. Most patients with dysphagia to solid food only and a normal EGD benefit from empiric esophageal dilation performed at the time of their endoscopy. In contrast, few patients with dysphagia to both solids and liquids respond.

Adult