Three candidate genes and angiotensin-converting enzyme inhibitor-related cough: a pharmacogenetic analysis

Unexplained, persistent cough limits the use of angiotensin-converting enzyme (ACE) inhibitors in a significant number of patients. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE, chymase, and B2-bradykinin receptor have been implicated. To investigate this question, we determined genotypes for common polymorphisms for these three genes in subjects with a history of ACE inhibitor-related cough. Specificity of the adverse effect was confirmed by a blinded, double-crossover design protocol in which subjects were rechallenged with either lisinopril or placebo. In 99 case subjects and 70 control subjects (who failed to develop cough on rechallenge with ACE inhibitor) thus selected, frequencies for the ACE D and I alleles were 0.56 and 0.44 (cases) and 0.56 and 0.44 (controls), respectively; frequencies for chymase A and B alleles (absence/presence of BstXI site) were 0.56 and 0.44 (cases) and 0.46 and 0.54 (controls), respectively; frequencies for B2-bradykinin receptor + and - alleles (presence/absence of a 21 to 29 nonanucleotide sequence) were 0.52 and 0.48 (cases) and 0.53 and 0.47 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for association between genotype at either gene examined and cough (adjusted for gender and age). Our data indicate that common genetic variants of ACE, chymase, and B2-bradykinin receptor do not explain the occurrence of ACE inhibitor-related cough.     

Predictive value of von Willebrand factor to ristocetin cofactor ratio and thrombin-antithrombin complex levels for hepatic vessel thrombosis and graft rejection after liver transplantation

Acute cellular rejection and hepatic vessel thrombosis are significant postoperative complications of liver transplantation. The study investigated changes in endothelial cell-related hemostatic proteins in the peripheral circulation of patients after liver transplantation, and assays for hemostatic parameters were compared with data from routine hematologic and biochemical investigations, together with clinical information. Of the 12 patients, 8 underwent acute rejection episodes. No significant differences in any hemostatic parameter measured were seen between rejection and nonrejection groups, with the exception of the platelet count, which increased after treatment of the rejection episode. Two of the 12 patients suffered fatal hepatic vessel thrombosis during the study. A number of significant differences were found between these patients and those with no thrombotic complications, most notably and increase in the von Willebrand factor antigen to ristocetin cofactor ratio and thrombin-antithrombin complex generation. These changes occurred before clinical detection of thrombosis. Thus, measurement of these parameters may be of predictive value in the diagnosis and monitoring of post-transplant thrombosis.     

Current practices of preoperative bowel preparation among North American colorectal surgeons

In North America, the rate of infections following colorectal surgery decreased after the introduction of oral antibiotic bowel preparation against colonic microflora. Eight hundred eight board-certified colorectal surgeons were surveyed for their current bowel preparation practices before elective procedures. The 471 responders (58%) all use mechanical preparation: oral polyethylene glycol solution (70.9% of the respondents), oral sodium phosphate solution with or without bisacodyl (28.4%), and "traditional" methods of dietary restriction, cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral neomycin and erythromycin or metronidazole are combined with a perioperative parenteral antibiotic. Most individuals start the preparation as outpatients the day before surgery, and the parenteral drugs are added to the regimen 1-2 hours before the procedure. The use of outpatient bowel preparation is increasing; however, patient selection is critical, and education is needed to reduce the rate of complications.     

正常固结饱和粘土的孔隙水压力

本文认为土体的剪胀性是偏应力的二次幂效应。根据这个假设,提出了孔隙水压力的计算公式。对正常固结饱和粘土的三轴不排水压缩试验结果进行了分析。分析结果表明,新的孔隙水压力公式合理地反映了正常固结饱和粘土的剪胀性。本文对土体的破坏问题也作了简要讨论。     

用于SiGeHBT器件的UHV/CVDn~-型硅外延研究

利用超高真空化学气相淀积(UHV/CVD)设备,在掺Asn+型Si衬底上生长了掺Pn-型Si外延层.用扩展电阻法分析了在不同的生长温度和PH3气体流量下生长的Si外延层的过渡区厚度.结果表明,生长温度对n+-Si衬底的As外扩有明显影响,在700℃下生长的Si外延层的过渡区厚度为0.16μm,而在500℃下仅为0.06μm,且杂质分布非常陡峭.X射线双晶衍射分析表明在700℃下生长的Si外延层的质量很高.制作的锗硅异质结晶体管(SiGeHBT)的击穿特性很硬,击穿电压为14.5V,在VCB=14.0V下的漏电流仅为0.3μA;输出特性很好,在VCE=5V,IC=3mA时的放大倍数为60     

In vivo evaluation of magnetite nanoparticles for use as a tumor contrast agent in MRI

Magnetite nanoparticles, coated by three different artificial polypeptides, were conjugated to an antibody specific to the carcinoembryonic antigen (CEA). To protect the particles from fast blood elimination, the coats were modified by various sugars, polyethyleneglycol, albumin, and sialoproteins, respectively. The protective effect was determined by using a specific in vitro test and by analyzing the biodistribution of the nanoparticles in nude mice grafted with CEA-tumors. In particular, a prolongation of the blood circulation time has been expected, if a natural modifier is attached to the coated nanoparticles. Although the elimination rate could hardly be decreased by any modifiers, the tumor accumulation is slightly improved by using the specific sialoprotein glycophorin B. The usefulness of nanoparticles as image contrast agents is probably limited by their microdistribution within the tumor tissue. The requirements for a contrast agent to be highly tissue specific are discussed.     

Expression of growth factors and their receptors in the postnatal rat cochlea

RT-PCR was used to assay for growth factors and receptors from seven different protein families in cochlea tissues of the juvenile rat. There was a broad representation of the growth factor families in all the cochlea tissues examined, though the organ of Corti and stria vascularis expressed a greater variety than the spiral ganglion. This broad expression suggests that a variety of known growth factors play significant roles in the development, maintenance, and repair of the inner ear. The results of this survey serve as a basis for the design of future in vitro experiments that will address the ability of growth factors to protect hair cells from damage and to evoke a repair-regeneration response by injured hair cells.