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Biomedical subjects

A Ramachandran

Publications and source records attributed to A Ramachandran.

At least 73 records · Page 4Linked to original sources
PubMed2001

Various presentations of postcholecystectomy bile leak diagnosed by scintigraphy.

Hepatobiliary scintigraphy is an established method for the diagnosis of a bile leak from the biliary system. A bile leak should be considered in any patient after cholecystectomy who has unexplained abdominal pain after operation. Three patients with bile leak diagnosed by scintigraphy are described, one of whom had an unusual pattern of hepatic subcapsular collection of the bile. The second patient had a bile leak through the postsurgical drainage tube, whereas the third patient had a more typical pattern of leakage into the peritoneal cavity.

Abdominal Pain↗
PubMed2001

Bone marrow biopsy and bone scan to detect skeletal metastases.

This study correlates the findings of bone marrow biopsy with those of bone scan in patients with common cancers and highlights the comparable sensitivities of the two methods at the authors' institution. The results show that bone scintigraphy may be slightly more sensitive than bone marrow examination for the detection of carcinomatous metastases. This experience suggests that institutions should devise clinical pathways based on their testing sensitivities and patient characteristics. These considerations will ultimately result in better and more cost-effective treatment of these patients.

Adult↗
PubMed2001

Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein.

Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

Animals↗
PubMed2001

Foot care economics--cost burden to diabetic patients with foot complications: a study from southern India.

OBJECTIVE: To estimate the direct cost burden of diabetic patients with foot complications. METHODS: An illustrative sample of 270 subjects with type two diabetes were seen at the clinic selected for the study. Among them 164 were without any complication (Group I) and 106 patients were with foot complications (Group II). In the latter group 83 (Group IIA) required in-patient (IP) care and 23 (Group IIB) required out-patient (OP) care. Annual expenses on medical care were estimated by a questionnaire method. Validation of the questionnaire data was verifying the amount spent by checking up the bills. RESULT: Group I spent Rs.4373 (US $ 104 Approx.), Group II spent Rs.15450 (US $ 343 Approx.), Group IIA spent Rs.7200 (US $ 171 Approx.) and Group IIB spent Rs.16910 (US $ 403 Approx.) in the study year. In the total sample of 270 subjects 61% were without foot problems, 22% had foot problems requiring OP treatment only (Group IIA), and 78% had foot problems requiring IP treatment (Group IIB). CONCLUSION: Group IIB spent significantly greater percentage of their income than Group IIA, and both groups spent greater percentage of their income than Group I. All differences were statistically significant.

Cost of Illness↗
PubMed2001

Association between ACE gene polymorphism and diabetic nephropathy in South Indian patients.

OBJECTIVE: To study the association of ACE gene polymorphism and diabetic nephropathy in South Indian subjects. SETTING: Outpatient clinic of a specialized hospital. PATIENTS: The study included 109 South Indian type 2 diabetic patients (72 males and 37 females; age 56.7 plus/minus 9.0 years, mean plus/minus SD). The patients were subdivided into two groups: nephropathic (n=86) and normoalbuminuric patients (n=23). INTERVENTIONS: Genomic DNA was isolated from the peripheral blood leukocytes. To determine the ACE genotype, genomic DNA was amplified by PCR initially using a flanking primer pair and, subsequently when necessary, with a primer pair that recognizes the insertion specific sequence for confirmation of the specificity of the amplification reactions. MAIN OUTCOME MEASURES: ACE genotype distribution in the two study groups. RESULTS: In the nephropathic patients, ID and DD genotypes were present in 52.3% and 27.9% of the patients, respectively as compared to 34.8% and 21.7% respectively in those with normoalbuminuria. The D allele was present in 80.2% of the nephropathic patients and 56.5% of the normoalbuminuric patients (chi-squared=4.28, P=0.039; odds ratio 3.12). Therefore, the higher percentage of II genotype in the normoalbuminuric group was 43.5% as compared to the 19.8% in nephropathic patients. CONCLUSIONS: This study showed a positive association between the D allele (ID and DD genotype) of the ACE polymorphism and diabetic proteinuria in South Indian type 2 diabetic patients. Our findings are in keeping with several earlier studies showing a strong association of the D allele of the ACE gene with diabetic nephropathy.

Alleles↗
PubMed2000

Phosphorylation of serine 51 in initiation factor 2 alpha (eIF2 alpha) promotes complex formation between eIF2 alpha(P) and eIF2B and causes inhibition in the guanine nucleotide exchange activity of eIF2B.

Phosphorylation of serine 51 residue on the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha) inhibits the guanine nucleotide exchange (GNE) activity of eIF2B, presumably, by forming a tight complex with eIF2B. Inhibition of the GNE activity of eIF2B leads to impairment in eIF2 recycling and protein synthesis. We have partially purified the wild-type (wt) and mutants of eIF2alpha in which the serine 51 residue was replaced with alanine (51A mutant) or aspartic acid (51D mutant) in the baculovirus system. Analysis of these mutants has provided novel insight into the role of 51 serine in the interaction between eIF2 and eIF2B. Neither mutant was phosphorylated in vitro. Both mutants decreased eIF2alpha phosphorylation occurring in hemin and poly(IC)-treated reticulocyte lysates due to the activation of double-stranded RNA-dependent protein kinase (PKR). However, addition of 51D, but not 51A mutant eIF2alpha protein promoted inhibition of the GNE activity of eIF2B in hemin-supplemented rabbit reticulocyte lysates in which relatively little or no endogenous eIF2alpha phosphorylation occurred. The 51D mutant enhanced the inhibition in GNE activity of eIF2B that occurred in hemin and poly(IC)-treated reticulocyte lysates where PKR is active. Our results show that the increased interaction between eIF2 and eIF2B protein, occurring in reticulocyte lysates due to increased eIF2alpha phosphorylation, is decreased significantly by the addition of mutant 51A protein but not 51D. Consistent with the idea that mutant 51D protein behaves like a phosphorylated eIF2alpha, addition of this partially purified recombinant subunit, but not 51A or wt eIF2alpha, increases the interaction between eIF2 and 2B proteins in actively translating hemin-supplemented lysates. These findings support the idea that phosphorylation of the serine 51 residue in eIF2alpha promotes complex formation between eIF2alpha(P) and eIF2B and thereby inhibits the GNE activity of eIF2B.

Alanine↗
PubMed2000

Attenuation of intestinal ischemia/reperfusion injury with sodium nitroprusside: studies on mitochondrial function and lipid changes.

Reactive oxygen species have been implicated in cellular injury during ischemia/reperfusion (I/R). Mitochondria are one of the main targets of oxygen free radicals and damage to this organelle leads to cell death. Reports suggest that nitric oxide (NO) may offer protection from damage during I/R. This study has looked at the functional changes and lipid alteration to mitochondria during intestinal I/R and the protection offered by NO. It was observed that I/R of the intestine is associated with functional alterations in the mitochondria as suggested by MTT reduction, respiratory control ratio and mitochondrial swelling. Mitochondrial lipid changes suggestive of activation of phospholipase A(2) and phospholipase D were also seen after (I/R) mediated injury. These changes were prevented by the simultaneous presence of a NO donor in the lumen of the intestine. These studies have suggested that structural and functional alterations of mitochondria are prominent features of I/R injury to the intestine which can be ameliorated by NO.

Animals↗
PubMed2000

Protease activation during surgical stress in the rat small intestine.

BACKGROUND: Surgical stress affects intestinal permeability and our earlier study using a rat model indicated that oxidative stress plays an important role in this process. Proteases are important mediators of cellular damage and are known to be activated in oxidative stress. This study looked at protease activity in enterocytes after surgical stress. METHODS: Surgical stress was induced by opening the abdominal wall and handling the intestine as done during laparotomy, in normal and xanthine oxidase-deficient rats. Enterocytes at various stages of differentiation were isolated and protease activity and protection offered by xanthine oxidase inhibitors were determined. Mitochondria and cytosol were prepared from total isolated enterocytes at different periods after surgical stress and protease activation was studied. RESULTS: Surgical stress induced activation of proteases in both the villus and crypt cells. Protease activation is seen in both mitochondria and cytosol, and similar to the other alterations in mucosal cells, protease activation was maximum 60 min after stress, returning to normal by 24 h. Thiol compounds modulate protease activity in both mitochondria and cytosol and the activation is not seen in xanthine oxidase-deficient animals. CONCLUSIONS: Surgical stress induces activation of proteases in villus and crypt cells of the small intestine. Both mitochondrial and cytosolic proteases are activated and free radicals generated by xanthine oxidase may mediate protease activation after surgical stress in the intestine.

Allopurinol↗
PubMed2000

Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin.

AIMS/HYPOTHESIS: Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (-55 c-->t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. METHODS: The -55 c-->t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. RESULTS: In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the -55 c-->t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). CONCLUSION/INTERPRETATION: The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females.

Adipose Tissue↗
PubMed2000

High prevalence and early onset of cardiac autonomic neuropathy among South Indian type 2 diabetic patients with nephropathy.

OBJECTIVE: This study was conducted to assess the adverse effects of diabetic nephropathy on cardiovascular autonomic neuropathy (CAN) in South Indian Type 2 diabetic patients. METHODS: Comparison was made between Type 2 diabetic patients with nephropathy (group 1, n=25), Type 2 diabetic patients without nephropathy (group 2, n=25) and non-diabetic, non-hypertensive control subjects (n=20). All had a detailed clinical and biochemical work-up and cardiac assessment by ECG. Cardiac dysautonomia was assessed by a battery of five non-invasive autonomic function tests (ANF) as recommended by Ewing and Clarke [D.J. Ewing, B.F. Clarke, Diagnosis and Management of autonomic neuropathy. Br. Med. J. 285 (1982) 916-918]. RESULTS: Group 1 patients showed a higher percentage of abnormal CAN function and a more severe form of CAN compared with patients in group 2. Group 1 patients showed early development of the abnormalities. They also had a higher prevalence of peripheral neuropathy compared with the patients without nephropathy. CONCLUSIONS: The present study showed that the presence of nephropathy was associated with the risk of cardiac autonomic neuropathy in Type 2 diabetic patients and it probably had an earlier onset also in them.

Adult↗
PubMed2000

Limitations of glycosylated haemoglobin as an index of glucose intolerance.

This study was conducted (a) to establish a normal cut-off value for glycosylated haemoglobin measured as HbA1c in South Indian subjects, and (b) to evaluate its usefulness in demarcating different categories of glucose intolerance. HbA1c measurement was carried out in 1261 cases with no known history of diabetes, while being tested by oral glucose tolerance test (M:F 850:411, mean age 40+/-12 years). An immunoturbidimetric procedure for HbA1c assay (Tina-Quant, Boehringer Mannheim, Germany) was used. The specificity and sensitivity of HbA1c in demarcating normal glucose tolerance (NGT) from abnormal tolerance were calculated using the ROC procedure. By the ROC analysis, a cut-off value of HbA1c > or = 6.0% gave a sensitivity of 88.5% and specificity of 62.8% using the WHO criteria (2-h plasma glucose > or = 200 mg/dl). Using the ADA criterion (fasting plasma glucose > 125 mg/dl) the sensitivity and specificity for the same cut-off value were 85.2 and 61.2%. In NGT, only a small percentage of the variance in HbA1c was explained by the fasting plasma glucose (FPG) values. The overall correlation coefficient between the fasting plasma glucose and HbA1c was r = 0.8, r2 = 0.64 and, in the case of 2-h post glucose, r = 0.82, r2 = 0.67. This showed that more than 35% of the variations in HbA1c were not explained by the plasma glucose values. The study showed that HbA1c values of > or = 6.0% gave a reasonably high sensitivity and specificity for diagnosis using the WHO or ADA criteria. However, nearly 35% of the variations in HbA1c were not explained by the variations in plasma glucose. Wide inter-individual variations even in the normoglycaemic range make the test unsuitable for diagnostic purpose.

Adult↗
PubMed2000

Expenditure on health care incurred by diabetic subjects in a developing country--a study from southern India.

The objective of the study was to estimate the direct costs of diabetes care to patients attending secondary care facilities in Madras, India. A total of 596 subjects were studied, at the Private Hospital for Diabetes Mellitus (PHD) (n = 422), and at the Government General Hospital (GGH) (n = 174). A simple interview schedule enabled a face to face interaction with the patients by the research investigator which elicited a frank and true response. The validity of the data collected was established by independent scrutiny of financial records in a sub sample. Payment bills for expenses of 140 subjects chosen on a random basis from the total sample of 422 PHD patients were compared with the costs reported by the subjects. There were no statistically significant differences both in the inpatient and the outpatient cases between the reported cost and actual cost. Median bill value (total costs)=Rs.1010 (range 195-16700) reported value=880 (110-20355) Z = -0.97, P = 0.33 and, for outpatients, median bill value=Rs.800 (195-4560) reported value=Rs. 740 (110-6320) Z = -1.56, P = 0.12. For inpatients, median bill value = Rs. 4235 (1289-16700) reported value=Rs.5459 (1285-20355), Z = -1.27, P5 years duration of diabetes spent more than those who had <5 years of duration; Rs.5570 (360-75200) and Rs.3220, (460-25600), respectively. All differences between these sub-groups were statistically significant. Within the ambit of economic aspects of the population in a developing country, the direct cost on diabetes health care is very high for many people.

Costs and Cost Analysis↗
PubMed2000

Vascular complications in young Asian Indian patients with type 1 diabetes mellitus.

To determine the prevalence of micro vascular and macro vascular complications in Asian Indian Type 1 diabetic subjects. There has been no major report on the prevalence of vascular complications in Type 1 diabetic patients in India. This study was done in Type 1 diabetic patients, aged < or =20 years at diagnosis of diabetes (n=617, M:F 322:295) with a minimum of 3 year follow-up. Standard diagnostic methodologies were used to test for micro vascular and macro vascular complications of diabetes. Retinopathy was detected in 13. 4% (background diabetic retinopathy 11.2%, proliferative diabetic retinopathy 1.9%, preproliferative 0.31%, maculopathy was seen in 13.3% of retinopathy cases), nephropathy in 7.1%, sensory neuropathy in 3.0%, ischaemic heart disease in 0.5% and peripheral vascular disease in 0.5% of the study subjects. Duration of diabetes showed positive association with retinopathy, nephropathy and neuropathy. Average glycosylated haemoglobin values, at follow up showed an association with retinopathy. Although the glycaemic control was suboptimal in the study group, prevalences of all complications, especially macro vascular complications were lower in Type 1 diabetic patients in this ethnic group, in comparison with the European or American counterparts.

Adolescent↗
PubMed2000

Postprandial hypertriglyceridaemia in treated type 2 diabetic subjects --the role of dietary components.

Postprandial hyperlipidaemia is a risk factor for cardiovascular diseases (CVD). This study was done (a) to evaluate whether postprandial hypertriglyceridaemia was common in Indian type 2 diabetic patients on treatment and (b) to see whether the high carbohydrate content of the diet was a cause of the lipid abnormality. Two hundred type 2 diabetic subjects (M:F, 137:63; mean age 51.6+/-10.2 years, mean BMI 25.5+/-3.1 kg/m(2)) with diabetes duration of 7.6+/-5.6 years were studied. Fasting and 2 h post prandial responses of plasma glucose and triglycerides (TG) were measured using a breakfast meal, usually consumed by the patient with the intake of usual hypoglycaemic drugs. Patients with a post prandial TG value greater than 15% of the corresponding fasting TG value were designated as group 2 and the remaining subjects as group 1. Dietary composition of the breakfast were calculated. Among the 200 subjects, 52 (26%) had post prandial TG higher than the fasting values. This was seen in patients who were consuming lower percentage of carbohydrates and higher percentage of fats than prescribed. Therefore the postprandial rise in TG was probably due to the high fat content of the diet and due to a lower insulin sensitivity. This study highlights the facts that postprandial hypertriglyceridaemia is seen only in a small proportion of the treated patients and the high carbohydrate diet does not produce hypertriglyceridaemia, either in the fasting or post prandial state. The minority who show an increased TG value at 2 h have been taking lower carbohydrate with higher fat content in the meal. This could have produced a lower insulin sensitivity in these patients.

Blood Glucose↗
PubMed2000

Familial aggregation of central obesity in Southern Indians.

BACKGROUND: High prevalence of diabetes in South Asians is associated with a pronounced tendency to abdominal obesity. This intermediate quantitative trait may be more amenable than type 2 diabetes to genetic linkage studies. OBJECTIVES: To derive a measure of central obesity independent of total adiposity and adjusted for factors under environmental influence, and to estimate the genetic contribution to familial aggregation of this trait. SUBJECTS AND METHODS: A total of 1,295 individuals from 300 families were studied in a community-based cross-sectional study in Chennai, India. Central fat was measured using sagittal abdominal diameter, and adjusted for age, BMI and body fat percentage measured by impedance. Intra-sibship correlations were calculated for adjusted sagittal abdominal diameter and a comparison variable, adjusted body fat percentage. RESULTS: Among individuals free of diabetes, intra-sibship correlations were 0.48 for adjusted sagittal abdominal diameter and 0.14 for adjusted body fat percentage. CONCLUSIONS: Even after adjustment for possible assortative mating, these results are consistent with a heritability exceeding 90% for a trait defined as abdominal fat accumulation adjusted for total adiposity, sex and age. Linkage studies of abdominal obesity that map one or more of the genes underlying this high heritability are therefore a possible route to identifying genes for type 2 diabetes in South Asians.

Abdomen↗
PubMed2000

Apoptosis in the intestinal epithelium: its relevance in normal and pathophysiological conditions.

Apoptosis is now recognized as an important process responsible for maintenance of the cellular balance between proliferation and death. Apoptosis is distinct from necrosis in that it is a programmed form of cell death and occurs without any accompanying inflammation. This form of cell death can be induced by a wide range of cellular signals, which leads to activation of cell death machinery within the cell and is characterized by distinct morphological changes. Apoptosis is especially relevant in the gastrointestinal tract, as the mammalian intestinal mucosa undergoes a process of continual cell turnover that is essential for maintenance of normal function. Cell proliferation is confined to the crypts, while differentiation occurs during a rapid, orderly migration up to the villus. The differentiated enterocytes, which make up the majority of the cells, then undergo a process of programmed cell death (apoptosis). Although apoptosis is essential for the maintenance of normal gut epithelial function, dysregulated apoptosis is seen in a number of pathological conditions in the gastrointestinal tract. The cellular mechanisms regulating this tightly regimented process have not been clearly defined and this topic represents an area of active investigation as delineation of this process will lead to a better understanding of normal gut mucosal growth.

Apoptosis↗
PubMed2000

Cosegregation of obesity with familial aggregation of type 2 diabetes mellitus.

OBJECTIVE: We have shown that a positive family history of diabetes, and the variables of general and central obesity are independent risk factors for type 2 diabetes in our population. This study was done to evaluate whether a familial predisposition to diabetes resulted in a tendency for adverse anthropometric and haemodynamic profiles in south Indian non-diabetic subjects. METHODS: The analysis was carried out on 2463 subjects (M: F, 1196: 1267) with normal glucose tolerance (NGT). The study subjects were selected from population surveys for diabetes. Details of age, sex, family history of diabetes, body mass index (b.m.i.), waist-to-hip ratio (WHR) and blood pressure were recorded. Serum cholesterol and triglycerides were estimated. RESULTS: A positive family history of diabetes was present in 24.7% of our subjects. Mean b.m.i. and percentage of obesity were significantly higher in families with a positive family history (group 2) vs. families with no family history (group 1). Subjects in group 2 had a higher 2-h plasma glucose (p < 0.001) and higher prevalence of hypertension (chi2 = 6.91, p = 0.0086). Factor analysis with principle components analysis (PCA) showed that a family history of diabetes clustered with WHR in men, and with b.m.i. and WHR in women. The b.m.i. formed a different domain with blood pressure in both sexes. WHR and b.m.i. clustered with cholesterol and triglycerides in another domain. CONCLUSIONS: In this population, general and central obesity are associated with a family history of diabetes. A family history of diabetes may increase the risk of hypertension and hyperlipidaemia indirectly through its connection with b.m.i.

Adipose Tissue↗