Chronic Arsenic Poisoning From Burning High-Arsenic-Containing Coal In Guizhou, China

Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.     

冠状动脉粥样硬化ADAMTS7新位点的发现和冠状动脉粥样硬化中ABO位点与心肌梗死的相关性:两项全基因组关联研究

<正>背景:该研究旨在评价在现有的冠状动脉粥样硬化的病变中,遗传因素对粥样硬化斑块进展及特异性心肌梗死是否存在显著作用。方法:对欧洲后裔参与者冠状动脉造影表型进行了两项全基因组关联研究(GWAS),为寻找冠状动脉疾病(CAD)易感性基因位点,研究比较了有异常(n=12393)和无异常的(对照组n=7383)个体;为寻找心肌梗死易感性基因位点,也同时比较了造影证实存在CAD并且有心肌梗死的个体(n=5783)与虽有CAD但无心肌梗死的个体(n=3644)。     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

Self-limiting extravasation in the unused urinary bladder

Patients being evaluated as potential renal transplant recipients routinely undergo voiding cystourethrography. Eight patients were encountered in whom extraperitoneal extravasation was noted from the region of the ureterovesical junction during voiding (seven patients) or during filling (one patient). Extravasation was bilateral in six patients and unilateral in two. The patients neither experienced symptoms related to the extravasation, required treatment, nor had sequelae. Five of the eight patients have subsequently received renal transplants and their bladders were observed to be normal at surgery. Cystoscopy was also performed in two of these five patients and was unremarkable. After transplantation, these patients' bladders functioned normally and gave rise to no symptoms.     

Changes in body temperature and urinary cortisol after routine immunization in babies with intrauterine growth retardation

Aim : To investigate whether infants with intrauterine growth retardation (IUGR) experience different changes in temperature and cortisol excretion after routine immunization compared with normal healthy infants. Methods : Overnight deep body temperature and urinary cortisol to creatinine ratios were measured on the night after immunization and a control night in normal and IUGR infants. Results : In 60 normal infants, first vaccination at about 10 wk of age led to a significant increase in minumum overnight temperature compared to the control night, mean rise 0.25°C (95% CI, 0.12 to 0.38). In 35 IUGR infants the mean rise in temperature between immunization night and control night was 0.35°C (95% CI, 0.15 to 0.55). The increases in minimum temperature did not differ significantly between the normal and IUGR infants ( p = 0.11). Cortisol to creatinine ratios measured from overnight urine samples showed that 23 IUGR infants had consistently higher levels than 39 normal infants; control night medians 34 and 15 ( p = 0.01) and immunization night medians 56 and 26 ( p= 0.02), respectively. However, the percentage increase did not differ significantly between the IUGR infants and the normal infants. A smaller number of second immunizations were studied, but no significant differences were found.

Conclusion : These results suggest that although the impact of immunization is the same for IUGR and normal infants, because IUGR infants are less mature and at greater stress before immunization, the absolute levels that they experience after immunization are higher than those for normal infants.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.