Physiology of cold-stored platelets

Platelet transfusions are a life-saving medical intervention used for the treatment of thrombocytopenia or hemorrhage. Extensive research has gone into trying to understand how to store platelets prior to the transfusion event. Much has been learned about storage bag materials, synthetic solutions, and how temperature impacts platelet viability and function. While room temperature storage of platelets preserves 24-hour in vivo platelet recovery and survival there is a greater risk for bacterial growth. Therefore, cold storage of platelets has become attractive due to the reduction in potential bacterial proliferation and the maintenance of platelet function beyond 5 days of storage. Cold stored platelets, however, have their own set of challenges. Cold stored platelets become activated through several mechanisms. The morphological and molecular changes that occur due to cold exposure enhance their ability to participate in the hemostatic process at the cost of rapid clearance from circulation. This review focuses on the underlying mechanisms leading to cold platelet activation and the receptor modifications involved in platelet clearance.     

一次采样测定人体咖啡因清除率的研究

咖啡因主要经肝细胞色素Ｐ４５０ＩＡ２代谢，测定其药代动国学参数可反映该Ｐ４５０亚型的活性。本研究显示咖啡因清除相为一级动力学；唾液和血浆的药代动力学参数有良好的相关性；含体重因素的清除率的变异系数比半减期小；用一次采样测定其清除率以８ｈ时点为宜。     

Impact of Ultrafiltration on Back-Diffusion in Hemodialyzer

Abstract: Ultrafiltration of water from blood to dialysate decreases the rate of back–diffusion of solutes from dialysate to blood. Therefore, back–clearance ( bK ) of hemodialyzers may be expressed as bK = bK _o – bTrQ _u, where bK _o is the diffusive back–clearance, bTr is the "back–"transmittance coefficient, and Qu is the net ultrafiltration rate. A formula for bK was derived from the one–dimensional theory of hemodialyzer, and bTr was described as a function of bK _o and the Staverman reflection coefficient. The transport parameters, bK _o and bTr , for creatinine and vitamin B₁₂ were measured in two types of hemodialyzers with negligible back–filtration, using water solutions, and compared with the transport parameters, K _o and Tr , for the case of both diffusion and ultrafiltration from blood to dialysate. bK _o was in general equal to K_o. bTr was not different from Tr for creatinine whereas bTr was lower than Tr for vitamin B₁₂. Experimental values of bTr for vitamin B₁₂ were in general agreement with theoretical predictions. However, experimental values of bTr for creatinine were lower than predicted values. We conclude that the impact of ultrafiltration on back–clearance for slowly diffusing solutes is weaker than on their clearance.     

Metabolic clearance rates of androgens and oestrogens in ageing women

Using the constant infusion technique we have measured the metabolic clearance rates (MCR) for Δ⁴-androstenedione (A), testosterone (T), oestrone (E₁) and oestradiol (E₂) in a large group of postmenopausal women. Their mean ± SE age was 64.5 ± 1.6 yr, their ages ranged from 46–90 yr. When the MCRs for each steroid were related to age by linear regression analysis no significant correlation was found for any of the steroids. Similarly, when the women were grouped according to their age by decade, the mean MCR for each steroid showed no trend with increasing age.

There was no difference in the MCRs for A, T and E₁ of the post-menopausal women and a large group of pre-menopausal women. However, there was a significant decrease in the mean MCR for E₂ between the two groups which is probably related to the marked decrease in circulating E₂ in postmenopausal women. We conclude that for these steroids age, per se, does not appear to be a major determinant of the MCR.     

Pharmacokinetics of cefradine, sulfamethoxazole and trimethoprim and their metabolites in a patient with peritonitis undergoing continuous ambulatory peritoneal dialysis

Cefradine and co-trimoxazole pharmacokinetics were studied in a patient with peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD). Concentrations in the plasma reached after oral administration of 500 mg cefradine four times daily and 400/80 mg co-trimoxazole four times daily were for cefradine 100g/ml, for trimethoprim 15g/ml, and for sulfamethoxazole 100/ml, respectively. In the dialysate concentrations were reached of 35–70/ml cefradine, 2–5/ml trimethoprim and 8–17g/ml sulfamethoxazole. The values for sulfamethoxazole are regarded too low to be clinically effective. Half-lives protein binding values and CAPD clearances are presented. Low CAPD clearances were obtained during the night and high values during the day. The dosage yielded too high plasma trimethoprim concentrations, while sulfamethoxazole dialysate concentrations were too low. It seems questionable therefore whether co-trimoxazole can be used orally for the treatment of CAPD peritonitis.     

男男性行为人群肛门人乳头瘤病毒16型和18型新发感染和自然清除的队列研究

目的 了解乌鲁木齐市MSM肛门HPV16型和18型的感染和自然清除情况。方法 采用动态队列研究的方法,按照队列研究样本量计算公式以HPV16型新发感染率估计样本量为712人。依托乌鲁木齐市MSM社会组织用滚雪球方式招募MSM 810名,每6个月随访1次。采集肛门脱落细胞分析HPV16型和18型感染率,利用Poission回归估计新发感染密度和持续感染密度,采用Cox比例风险模型探寻新发感染、持续感染和感染自然清除的影响因素。结果 招募MSM 810名,将随访次数≥2次的482名MSM纳入分析,随访994.7人年,随访次数和随访时间的M（P₂₅,P₇₅）分别为4（3,5）次和2.2（1.8,2.6）年。HPV16型和18型的基线感染率分别为8.5%（41/482）和3.3%（16/482）,两型基线混合感染率为0.6%（3/482）。HPV16型和18型的首次新发感染密度分别为10.06（95%CI：8.12~12.45）/100人年和5.24（95%CI：3.95~6.96）/100人年;HPV16型和18型感染自然清除率分别为71.2%（89/125）和71.8%（46/64）,HPV18型随访1.5年的感染自然清除率高于HPV16型（97.7%比94.1%）。HPV16型和18型的持续感染率分别为4.5%（20/441）和1.7%（8/466）。无婚史者比有婚史者的HPV16型持续感染风险低（aHR=0.29,95%CI：0.12~0.71）。最近6个月肛交未使用安全套者HPV18型自然清除率是使用安全套者2.63倍（95%CI：1.08~6.42）。结论 乌鲁木齐市MSM HPV16和18型新发感染较常见,自然清除率均较高。相比于HPV18型,HPV16型有更高的新发感染率和持续感染率,自然清除率低,致病风险较大。     

股骨头钻孔骨移植髋关节外支撑治疗股骨头无菌坏死

探讨股骨头钻孔管移植髋关节外支撑治疗股骨头无菌坏死的疗效。方法 :股骨头钻孔去除坏死骨加上腓骨骨移植 ,髋关节外支撑架固定。结果 :治疗成人股骨头坏死1 1例 ,男 8例 ,女 3例 ;平均年龄 40岁 ,平均病史 2年 ;本组Ⅰ～Ⅲ期 8例 ,Ⅲ～Ⅳ期 3例 ;随访2年 ,优良率 86 6 %。结论 :本术式优点是 :注重彻底清除坏死骨 ,髋关节外植骨 ,早期负重。     

Capacity-limited renal glucuronidation of probenecid by humans A pilotVmax-finding study

Probenecid shows dose-dependent pharmacokinetics. When in one volunteer the dose is increased from 250 to 1,500 mg orally, thet _1/2 increased from 3 to 6 h. TheC _max was 14g/ml with a dosage of 250 mg, 31g/ml with 500 mg, 70g/ml with 1,000 mg and 120g/ml with 1,500 mg. Thet _max remained 1 h for all four dosages. The AUC/dose ratio increased with the dose, indicating nonlinear elimination. The total body clearance declined from 64.5 ml/min for 250 mg to 26.0 ml/min for 1,500 mg. The renal clearance of probenecid remained constant, 0.6–0.8 ml/min. Protein binding of probenecid is high (91%) and independent of the dose. The phase I metabolites show lower protein binding values (34–59%). The protein binding of probenecid glucuronidein vitro (spiked plasma) is 75%. Probenecid is metabolized by cytochrome P-450 to three phase I metabolites. Each of the metabolites accounts for less than 10% of the dose administered; the percentage recovered in the urine is independent of the dose. The main metabolite probenecid glucuronide is only present in urine and not in plasma. The renal excretion rate-time profile of probenecid glucuronide shows a plateau value of approximately 700g/min (46 mg/h) with acidic urine pH. The duration of this plateau value depends on the dose: 2 h at 500 mg, 10 h at 1,000 mg and 20 h at 1,500 mg. It is demonstrated that probenecid glucuronide must be formed in the kidney during its passage of the tubule. The plateau value in the renal excretion rate of probenecid value reflects itsV _max of formation.     

Disposition of quinine in rats with induced renal failure

Aetiologically different models of experimental acute renal failure were induced in rats by the administration of glycerol, mercuric chloride and gentamicin, respectively, to different groups. Quinine levels in plasma and urine of the rats with induced renal failure were determined and pharmacokinetic parameters (eliminationt _1/2, CL _p ,V, CL_R AUC_0–) of the drug were derived and compared with values obtained from control rats following intraperitoneal administration of a 10 mg/kg body-weight dose of quinine. Results showed that each of the three compounds caused an up to 25-fold increase in the plasma levels of the drug and a marked decrease in the levels of the metabolite 3-hydroxyquinine. All the pharmacokinetic parameters determined for the rats with renal impairment were markedly different when compared to control. The high plasma quinine levels observed in the rats with renal failure could be largely due to the marked decrease inV and reduced metabolism. Also, in the rats with renal impairment, no correlation was observed between the increased plasma urea levels and plasma quinine levels or disposition of the drug. The results of the study suggest that quinine should be used with caution in patients with renal impairment. The plasma urea levels, as a measure of renal function, might not provide a suitable index for determining quinine dosage.