Clinical implication of multiple risk factor control in the management of diabetic macrovasucular complications

Using cross-sectional and prospective analyses, the risk factors for macroangiopathy (MA) in nonobese Type 2 diabetic patients were evaluated. In the cross-sectional study, we determined a cutoff point for each variable at which changes in the prevalence of total MA reached statistically significant levels. In the prospective study, those who met more than four out of seven control criteria as set forth in the Multiclinical Study for Diabetic Macroangiopathy (MSDM) had less risk of MA in Type 2 diabetes initially diagnosed without MA compared with those who fulfilled less than three factors. These results suggest that multiple risk factor control is the most effective and reasonable way to lower the incidence of MA in Type 2 diabetes.     

An atypical case of "Takotsubo cardiomyopathy" during alcohol withdrawal: abnormality in the transient left ventricular wall motion and a remarkable elevation in the ST segment

A 64-year-old man was admitted due to hypokalemia-related myopathy. He was heavy drinker. He felt the stress of alcohol withdrawal during his hospitalization. The patient suffered a cardiopulmonary arrest lasting approximately 5 minutes on the fifth hospital day. One day later, ST-segment elevation was observed in leads I, aV(L), and V(2-6). Emergent cardiac catheterization was performed for suspicion of acute myocardial infarction. Normal coronary arteries with anterior akinesis of the left ventricle were revealed during the procedure. The present case may be an atypical form of "Takotsubo cardiomyopathy" in which the left ventricular contraction is due to focal anterior wall motion abnormalities.     

Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

An accelerated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl-D-glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats. The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.     

Virus-associated hemophagocytic syndrome in an international traveler as a differential diagnosis of SARS

During the epidemic of severe acute respiratory syndrome in 2003, a 27-year- old Japanese woman presented a high fever and acute respiratory distress with pulmonary infiltrates after traveling to a high-risk area. An alternative diagnosis was made as Epstein-Barr virus-associated hemophagocytic syndrome, based on the proliferation of macrophages with hemophagocytosis in the bone marrow and Epstein-Barr viral marker profiles. Virus-associated hemophagocytic syndrome in an international traveler should be included in the differential diagnosis of severe acute respiratory syndrome.     

Efficacy and anticarcinogenic activity of interferon for hepatitis C virus-related compensated cirrhosis in patients with genotype 1b low viral load or genotype 2

Background: We assessed the efficacy and anticarcinogenic effects of interferon (IFN) therapy in patients with hepatitis C virus (HCV)-related cirrhosis. Methods: The study subjects were 123 Japanese patients with HCV-related cirrhosis with genotype 1b low viral load or genotype 2 who received IFN from 1989 to 2005 (18 patients continue to receive IFN therapy). They included 81 men and 42 women aged 29-74 years (median, 56 years). Results: Univariate analysis identified four parameters that significantly influenced SVR; viral load (low HCV concentration, P < 0.001), duration of IFN therapy (>/= 52 weeks, P = 0.029), daily dose of IFN (>/= 6 million units, P = 0.018), induction therapy (presence, P = 0.010) and choline esterase (> 1.0 DeltapH, P = 0.037). Multivariate analysis identified viral load (risk ratio = 6.329, P < 0.001) and daily dose of IFN (risk ratio = 2.62, P = 0.042) as two independent parameters thatinfluenced SVR. During the observation period, newly developed hepatocellular carcinoma (HCC) was detected in 22 patients. The rates of development of HCC in patients with SVR were 5.8% at the fifth year and 10.3% at the 10th year, compared with 25.8% at the fifth year and 42.5% at the 10th year in non-SVR patients. Multivariate analysis showed that IFN efficacy (SVR) was the only independent factor of hepatocarcinogenesis (hazard ratio: 0.185, 95% confidence interval: 0.042-0.810, P = 0.025) Conclusion: Among patients with HCV-related cirrhosis, the rate of development of HCC is significantly less in patients with SVR.     

Endothelin-3 immunoreactivity in gonadotrophs of the human anterior pituitary.

Endothelin (ET), originally discovered in vascular endothelial cells, has also been demonstrated in nonvascular tissues. The present study was undertaken to elucidate the presence of ET in the human pituitary. The avidin-biotin complex method with antiserum to ET-1 (and ET-2) or ET-3 was used to identify ET in human pituitaries obtained by autopsy. ET-3 immunoreactivity was found in the cytoplasm of large ovoid cells of the anterior pituitary. Using the double staining method, the cells containing ET-3 immunoreactivity were differentiated from cells containing ACTH, TSH beta, GH, PRL, and protein S-100. By staining with anti-LH beta antiserum in adjacent sections and using the double staining method, the cells were identified as gonadotrophs. No staining was observed in the posterior pituitary. In addition, no ET-1 (and ET-2) immunoreactivity was detected. The specific localization of ET-3 immunoreactivity in the gonadotrophs of the human pituitary suggests a possible role of ET-3 in the regulation of anterior pituitary function.