Ethnicity modifies the relation between fasting plasma glucose and HbA1c in Indians, Malays and Chinese.

AIMS: To study whether HbA(1c) , and its relationship with fasting plasma glucose, was significantly different among Chinese, Malays and Indians in Singapore. METHODS: A sample of 3895 individuals without known diabetes underwent detailed interview and health examination, including anthropometric and biochemical evaluation, between 2004 and 2007. Pearson's correlation, analysis of variance and multiple linear regression analyses were used to examine the influence of ethnicity on HbA(1c) . RESULTS: As fasting plasma glucose increased, HbA(1c) increased more in Malays and Indians compared with Chinese after adjustment for age, gender, waist circumference, serum cholesterol, serum triglyceride and homeostasis model assessment of insulin resistance (P-interaction < 0.001). This translates to an HbA(1c) difference of 1.1 mmol/mol (0.1%, Indians vs. Chinese), and 0.9 mmol/mol (0.08%, Malays vs. Chinese) at fasting plasma glucose 5.6 mmol/l (the American Diabetes Association criterion for impaired fasting glycaemia); and 2.1 mmol/mol (0.19%, Indians vs. Chinese) and 2.6 mmol/mol (0.24%, Malays vs. Chinese) at fasting plasma glucose 7.0 mmol/l, the diagnostic criterion for diabetes mellitus. CONCLUSIONS: Using HbA(1c) in place of fasting plasma glucose will reclassify different proportions of the population in different ethnic groups. This may have implications in interpretation of HbA(1c) results across ethnic groups and the use of HbA(1c) for diagnosing diabetes mellitus.

The role of single nucleotide polymorphisms (SNPs) in understanding complex disorders and pharmacogenomics.

INTRODUCTION: In the last two years, there has been an increasing interest in single nucleotide polymorphisms (SNPs). They have been hailed as the most common polymorphism found in the human genome and are believed to be responsible for 90% of all inter-individual variation. Efforts are now directed at the large-scale identification and archiving of SNPs in the human genome. Not only are they useful markers for population divergence studies, SNPs can be utilised as markers in studies of complex diseases and pharmacogenomics. METHODS: Traditional methods for identifying SNPs, as well as methods for large-scale detection and genotyping of SNPs currently being developed, are briefly discussed in this review. Such developments will facilitate and enhance the process of identifying and characterising genes and their functions. RESULTS: The utility of SNPs in identifying genes contributing to pharmacogenetic variation and increased risk of a complex disease is discussed. The role of SNPs in influencing drug response in different individuals is also presented. CONCLUSIONS: In helping to unravel the genetic basis of complex diseases and inter-individual variation in drug response, SNPs will catalyse the transition into a new age of medicine in which medical care is tailored to the individual's genetic profile.

Power Doppler-derived speckle tracking image of intraventricular flow in patients with anterior myocardial infarction: correlation with left ventricular thrombosis.

The abnormal spatial distribution of intraventricular flow is superior to clinical and two-dimensional (2-D) echocardiographic variables in predicting left ventricular thrombosis after myocardial infarction. Echocardiography was prospectively performed in 79 patients within 72 h after anterior wall myocardial infarction onset and repeated before discharge. The apical rotating flow pattern in color flow map was recognized as abnormal. By power Doppler echocardiography, the moving blood could generate speckle tracking images to delineate the intraventricular flow. A swirling flow pattern indicating the compartmentalization of left ventricular blood flow with some blood stagnant in the apical dyssynergic area was identified. The flow pattern shown by the speckle tracking image was superior to the color-flow map in correlating with left ventricular thrombosis. It implicated that the more the detail in which we can describe the blood flow pathway, the more information we can realize.

Dobutamine stress echocardiography for detecting coronary artery disease.

To assess the value of dobutamine stress echocardiography (DSE) to detect coronary artery disease (CAD) and to compare the diagnostic accuracy between DSE and treadmill exercise test (TXT), 104 patients (mean age 58 +/- 12 years) presenting for coronary angiography were prospectively studied. TXT was performed according to the Bruce protocol. Dobutamine (5-40 micrograms/kg/min) was infused in 3-min stages. Digital echocardiograms were recorded on-line at baseline, during low- and peak-dose dobutamine infusion, and at recovery. An echocardiogram positive for CAD was defined as the one showing a new wall motion abnormality (WMA) induced by dobutamine. There were no major complications during the study. Significant CAD (> or = 50% diameter stenosis) was present in 17 of 30 patients who had normal echocardiograms at baseline. The sensitivity for detecting CAD was 76% by TXT and 94% by DSE, and the specificity was only 38% by TXT and 92% by DSE, respectively. Seventy-four patients had localized rest WMAs. Twenty-four had no significant CAD or lesions only confined to regions with abnormal rest wall motion, and 50 had disease remote from these regions. The sensitivity for detection of remote disease was 60% by TXT and 76% by DSE, and the specificity was 75% by TXT and 96% by DSE, respectively. In conclusion, DSE is a safe and accurate diagnostic tool for identifying CAD and for predicting the extent of disease in those who have localized rest WMAs.

Protection of a rat tracheal epithelial cell line from paraquat toxicity by inhibition of glucose-6-phosphate dehydrogenase.

Transformed rat tracheal epithelial cells (U2) were found to be 3.6-fold more sensitive than lung fibroblasts (RLF) to paraquat. Although the toxic effects of paraquat are associated with the generation of very active superoxides, U2 cells contained higher levels of superoxide dismutase and catalase than RLF cells. On the other hand, the specific activities of both NADPH-cytochrome c reductase and glucose-6-phosphate dehydrogenase (G6DP) were 3- to 4-fold higher in U2 cells than in RLF cells. Treatment with dehydroepiandrosterone (DHEA) and epiandrosterone (EPI), G6PD inhibitors, significantly decreased the intracellular NADPH and protected U2 cells from paraquat toxicity. Since DHEA and EPI treatment did not affect the uptake of paraquat, our results suggest that paraquat sensitivity may depend on the redox cycling-associated activities of paraquat.

Suppression of sodium arsenite-potentiated cytotoxicity of ultraviolet light by cycloheximide in Chinese hamster ovary cells.

Post-treatment with sodium arsenite synergistically increased the cytotoxicity of ultraviolet (UV) light. The potentiation of UV cytotoxicity by sodium arsenite was apparently suppressed by cycloheximide (CHM), a protein synthesis inhibitor. The protective effect of CHM against sodium arsenite-potentiated UV cytotoxicity was well correlated to its activity in inhibiting the synthesis of stress proteins, particularly a small polypeptide with a molecular weight of 8500 dalton. This small stress protein was demonstrated as ubiquitin by immunoprecipitation. Our results also showed that neither ubiquitin induction nor potentiation of UV cytotoxicity by post-treatment with sodium arsenite was observed in the stationary cells. Thus, we suggested that ubiquitin is possibly involved in the action of arsenite in potentiating UV-induced cell killing.

Effects of sodium arsenite on the cytotoxicity of bleomycin.

Our present data show that posttreatment with sodium arsenite has no effect on the cytotoxicity of bleomycin (BLM), a radiomimetic agent, in Chinese hamster ovary (CHO) cells, human skin fibroblasts, and HeLa cells. However, pretreatment with sodium arsenite potentiated the cytotoxic effects of BLM in CHO cells. This effect decreased with increasing time interval between the treatments with sodium arsenite and BLM. BLM-inactivating activity was markedly reduced in cells pretreated with sodium arsenite. Furthermore, both arsenite-potentiated BLM cytotoxicity and arsenite-reduced BLM-inactivating activity were abolished by cycloheximide. These results suggest that the potentiation effect of sodium arsenite on BLM cytotoxicity may be due to the decrease of BLM-inactivating activity. In addition, only a slight increase in G2 phase population and no apparent change in intracellular glutathione levels were observed in CHO cells pretreated with sodium arsenite.

Clinical and immunopathologic study of mesangial IgM nephropathy: report of 41 cases.

Forty-one out of 408 cases (or 10%) of primary glomerular disease had diffuse fine granular to arc-like short linear mesangial deposits of IgM by direct immunofluorescence. The IgM deposition was accompanied by C1q and/or C4 in the same locality in 29 cases, by C3 in 10, and by trace amounts of IgA in 6. Properdin-factor B was not detected. Fine granular electron dense deposits of low density were detected in the mesangium in all 41 cases by electron microscopy, usually as a discrete granular or arc-like pattern beneath the mesangial glomerular basement membrane and correlated well with the immunofluorescence findings. An immune complex disease with complement activation via the classical pathway is suggested. The ages of the patients varied from 2 to 58 years (average 23.8 years). A male predominance of 2.2:1 was identified. Serum IgM level was elevated in 46.7% of the cases. The majority (87.8%) of the cases manifested a nephrotic syndrome or relapse at time of biopsy, and the remaining cases experienced persistent or intermittent proteinuria. Among the 36 nephrotic patients, 22 cases (61.1%) demonstrated complete remission with steroid therapy, 9 cases (25%) were resistant, and 5 cases (13.9%) had partial remission. Complete and partial remissions were later achieved with cytotoxic drugs or methylprednisolone pulse therapy in 3 and 4 cases respectively in the steroid resistant patients. Frequent relapses occurred during the course in 22 out of 32 cases (68.8%) who had experienced complete or partial remission. Follow-up study after biopsy demonstrated that sustained complete remission was achieved with prednisolone with or without cytotoxic drugs and pulse therapy in only 14 (42.4%) of the 33 nephrotic cases who had been followed up for longer than 6 months, and six of them had had previous relapses. Pathologically, 56.1% of the patients showed mild to moderate increase in mesangial matrix and cellularity. Focal and segmental sclerosis was demonstrated in four cases (9.8%). However, minimal glomerular change was also common (34.1%). The patients with minimal change seemed to have a higher complete remission rate than patients with more evident glomerular alterations, although the difference was not statistically significant. This clinical and immunopathological study suggests that mesangial IgM nephropathy is an important disease in Taiwan, with a variable response to treatment and frequent relapses.(ABSTRACT TRUNCATED AT 400 WORDS)