In vitro anti-HIV-1 antibody production in subjects in different stages of HIV-1 infection.

We evaluated the in vitro antibody production from peripheral blood mononuclear cells (PBMC) against HIV-1 proteins in infected adults. Fifty-four HIV-1 infected patients (four recent seroconverters, 15 asymptomatics with a CD4 count higher than 500/microliters, 27 asymptomatics with a CD4 count between 200 and 500/microliters and eight symptomatic patients) were tested. PBMC were incubated in the presence or absence of 1% pokeweed mitogen (PWM) at 37 degrees C for 8 days. Western blot assay, p24 antigen ELISA and anti-p24 antibody ELISA were performed on serum and culture supernatants. Spontaneous production of anti-env antibody in culture supernatants was evidenced in all subjects. All the positive supernatants for anti-core antibodies (18/54) were derived from asymptomatic patients. PBMC from recent seroconverters and from symptomatic patients did not produce any anti-core antibody. Antibody production decreased after stimulation with PWM. The concentration of p24 antigen did not significantly increase in p24 positive supernatants following acidification (P = 0.1), suggesting that the inability to detect p24 antibody was not due to the anti-p24 antibody complexed to p24 antigen in culture supernatants. In vitro production of anti-p24 antibodies was significantly more frequent in asymptomatic subjects with high CD4+ cell counts (P = 0.02) and was absent in recent seroconverters. This last finding suggests that during the initial phases of the infection, anti-p24 antibody production may be restricted to cells residing in lymphoid organs. In addition, the lower percentage of anti-core antibody in people with low CD4+ cell counts is not merely a consequence of the binding of the antibody to an increased amount of antigen, but probably reflects an impaired production or a sequestration of producing cells in lymphoid tissue during the late stages of the infection.     

Hepatitis B virus (HBV)-specific in vitro antibody production by peripheral blood mononuclear cells (PBMC) after vaccination by recombinant hepatitis B surface antigen (rHBsAg)

To study the immunization induced by rHBsAg, we analysed the in vitro antibody production (IVAP) to HBsAg by PBMC from 18 subjects vaccinated by two injections on days 0 and 30. HBsAg-specific IVAP was detectable in all subjects after both the first and the second injection, and lasted for about 10 days and then disappeared. However, when the spontaneous HBsAg-specific IVAP became negative, HBsAg stimulation of PBMC cultures induced again a specific HBsAg IVAP. Cultures of cell populations separated by erythrocyte rosetting or Percoll density centrifugation showed that the cells responsible for spontaneous secretion, after in vivo stimulation, were low-density B lymphocytes. High-density B lymphocytes were involved in anti-HBs production induced by in vitro stimulation when spontaneous secretion disappeared. These data suggest that the IVAP test could be a source of important information along with serologic analysis for exploration of the immune response to hepatitis B vaccine.     

实体瘤化疗患者植入式静脉输液港治疗的相关感染并发症及危险因素分析

目的:对实体瘤化疗患者行植入式静脉输液港治疗的临床感染并发症及感染率进行分析,探究引起患者相关感染并发症的危险因素。方法:纳入2016年1月至2018年6月在我院介入科接受数字减影血管造影（DSA）引导植入式静脉输液港（IVAP）治疗的实体瘤化疗患者495例进行研究,对患者植入IVAP治疗期的病情进展情况、相关感染并发症及感染率进行回顾性分析,并将可能引起感染并发症的危险因素进行单/多因素分析。结果:495例入组患者中因故拔除IVAP 269例（54.34%）,输液港使用时间约为（335±210）d;持续使用IVAP患者226例（45.66%）,输液港使用时间约为（368±334）d。39例（7.88%）出现IVAP相关感染,其中早期感染并发症8例（20.51%）,晚期感染并发症31例（79.49%）。单因素分析结果显示,穿刺点、化疗方案是显著引起相关感染并发症的初始因素,组间差异具有统计学意义（P＜0.05）。多因素分析结果显示,化疗方案是引起相关感染并发症的危险因素（P＜0.05）。结论:化疗方案是实体瘤化疗患者行植入式静脉输液港治疗期引起相关感染并发症的独立危险因素。     

Cardiovascular disease in the elderly

The aging of the population worldwide will result in increasing numbers of elderly patients, among whom heart disease is the leading cause of death. Changes in cardiovascular physiology with normal aging and prevalent comorbidities result in differences in the effects of common cardiac problems as well as the response to their treatments. Patient-centered goals of care such as maintenance of independence and reduction of symptoms may be preferred over increased longevity. New less-invasive treatments are likely to improve outcomes in elderly patients who previously have been considered at prohibitive risk for traditional procedures. Clinical trials enrolling elderly patients are limited and recommendations for management from younger patients frequently lack evidence-based support in patients aged >75 years.Full English text available from: www.revespcardiol.org     

Differentiation of Gut and Hepatic First-Pass Effect of Drugs: 1. Studies of Verapamil in Ported Dogs

Purpose. To investigate the relative contributions of the gut and liver to the first-pass loss of verapamil (VL) using anin vivo intestinal-vascular access port (IVAP) dog model. Methods. Basic pharmacokinetics of VL were determined after intravenous (IV: 0.5 mg/kg), portal venous (PV: 2 mg/kg), and duodenal (ID: 2 mg/kg) administration in IVAP dogs. Serial blood samples were collected for 8 h after dosing, and plasma was analyzed for unchanged drug by a high-performance liquid chromatography-fluorescence method. Extraction ratios in the liver and intestinal tract were determined from the area under the concentration-time curves for ID, PV, and IV administration. The functional role of CYP450 or secretory transporters such as P-gp on the gut and liver first-pass loss of VL was further studied using ritonavir, a known substrate or inhibitor of these processes. Results. The liver had a high intrinsic capacity for clearing VL because the absolute bioavailability (BA) of VL was 21.7% after PV administration. The BA of VL after ID administration was 23.5%; therefore, intestinal absorption was complete and intestinal extraction was negligible (ER_GI 0). The BA of VL increased from 23.5% to 66.2% in the presence of ritonavir primarily due to a reduction in hepatic extraction. Conclusions. Although the liver had a high intrinsic capacity for extracting VL, the contribution of gut to the first-pass loss of VL was negligible. Because of the additive effects of intestinal CYP3A-mediated metabolism and secretory transport, a significant gut first-pass effect was expected, but not observed in dogs. These studies demonstrate the utility of the in vivo IVAP dog model for evaluating the relative contribution of the gut and liver to the first-pass loss of drugs and for characterizing the functional role that CYP450 metabolism and/or secretory transporters play in drug-drug interactions and reduced oral bioavailability.     

肿瘤化疗患者并发输液港导管相关血栓的危险因素及治疗策略

目的 探讨肿瘤化疗患者并发输液港(implantable venous access port,IVAP)导管相关血栓的危险因素,并分析治疗策略。方法 2021年3—7月前瞻性连续纳入复旦大学附属中山医院274例使用输液港化疗的肿瘤患者。超声筛查患者IVAP导管相关血栓发生情况,并以此分为血栓发生组和未发生IVAP导管相关血栓组。搜集患者基线和病历资料,多因素Logistic回归分析肿瘤化疗患者并发IVAP导管相关血栓的危险因素,并对发生血栓的患者进行3个月的初步抗凝治疗(D-二聚体<0.8 mg/L的患者用10 mg/d利伐沙班抗凝,D-二聚体≥0.8 mg/L的患者用20 mg/d利伐沙班抗凝),随访发生血栓组患者的治疗结果。结果 274例肿瘤患者中有35例(12.8%)患者发生IVAP导管相关血栓。多因素Logistic回归分析表明发生相关血栓的独立危险因素包括合并有远处转移(OR=3.013)、化疗前纤维蛋白原≥400 mg/dL(OR=3.226)、新辅助+辅助化疗方式(OR=26.286)。随访发现所有IVAP导管相关血栓阳性患者抗凝用药后无局部症状发生或加重,患者均未出现肺栓塞,1例因肠道出血停药,1例轻度牙龈出血,1例轻度鼻黏膜出血。有超声复查的5位患者在新型口服抗凝药作用下附壁血栓消失或变小。结论 IVAP相关血栓的危险因素为化疗前纤维蛋白原≥400 mg/dL、有远处转移、新辅助+辅助化疗方式,临床应注意筛查。D-二聚体<0.8 mg/L的患者可使用10 mg/d的利伐沙班;D-二聚体≥0.8 mg/L的患者可使用20 mg/d的利伐沙班抗凝。