Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

近红外光谱仪监测窒息新生儿听觉刺激诱发时的脑氧合代谢及脑血流变化

目的了解窒息新生儿在听觉刺激诱发脑神经活动时的脑氧合代谢和脑血流量的改变。 方法1998~2003年北京中日友好医院儿科选择窒息新生儿34例为窒息组，健康新生儿40名为对照组。使用近红外光谱仪，观察听觉刺激试验诱发的脑氧合血红蛋白\[Hb O2\]、还原血红蛋白\[Hb H\]和总血红蛋白\[Hb tot\]浓度的变化，并比较两组脑氧合代谢和脑血流量的改变。根据\[Hb O2\]、\[Hb H\]和\[Hb tot\]不同的变化，将氧合代谢曲线分为A(\[Hb O2\]、\[Hb H\]和\[Hb tot\]均增加)； B(\[Hb O2\]和\[Hb tot\]增加,\[Hb H\]降低)；C(\[Hb O2\]和\[Hb tot\]降低,\[Hb H\]增加)3种曲线类型。 结果窒息组中25例(25/34、73.5%)显示C型变化，对照组中28例(28/40、70.0%)显示A型变化，两组中A、C两型例数比较差异显著(P<0.05)。两组\[Hb O2\]和\[Hb tot\]数值变化幅度比较差异显著(P<0.05)。 结论窒息新生儿听觉刺激诱发相应皮层的神经活动时，显示局部脑血流量下降、氧合代谢降低，重度窒息儿更明显。     

Phosphoinositide hydrolysis linked 5-HT2 receptors in fibroblasts from choroid plexus

A serotonin (5-HT)-mediated phosphoinositide hydrolysis response was characterized in fibroblasts cultured from rabbit choroid plexus. 5-HT elicited a maximum 8-fold increase in [³H]inositol-phosphate ([³H]IP) formation, while the partial agonists, (+)-lysergic acid diethylamide and (−)-1-(4-bromo-2,5-dimethyoxyphenyl)-2-aminopropane caused 2- and 5-fold increases, respectively. Mianserin, ketanserin, and spiperone were equipotent at blocking the 5-HT-mediated response. Thus, agonist and antagonist profiles indicate interactions with 5-HT₂ receptors.     

脐血单核细胞对VD大鼠认知功能及脑组织BDNF的影响

目的观察颈内动脉输注脐血单核细胞(Human cord blood mononuclear cells,HCMNCs)对血管性痴呆(Vascular dementia,VD)大鼠认知功能及脑组织脑源性神经营养因子(Brain-derivedneurotrophicfactor,BDNF)含量的影响。方法改良Pulsinellis四血管阻断法建立VD大鼠模型;体外分离HCMNCs,术后24h颈内动脉输注数量为3×106/0.5ml的BrdU标记细胞;利用穿梭箱系统和ELISA法检测注射HCMNCs后2、4、8周VD大鼠学习记忆能力以及脑组织BDNF含量的变化。结果模型组大鼠主动回避反应比率明显低于对照组(P<0.01),治疗组较模型组显著提高(P<0.01)。术后2周模型组大鼠脑组织BDNF含量较对照组明显增高(P<0.01),4周时达到高峰(P<0.01),8周时则明显下降,与2周时相比有显著性差异(P<0.05);颈内动脉输注HCMNCs后治疗组大鼠脑组织BDNF含量较模型组显著升高(P<0.01),4周时最高(P<0.01),8周时略有下降,但仍维持在较高水平,与4周时相比无显著性差异(P>0.05)。结论颈内动脉输注HCMNCs可显著改善VD大鼠学习记忆能力,增加VD大鼠脑组织BDNF含量,具有脑保护作用。     

无水酒精阻滞大鼠腹腔神经丛后脊髓、孤束核C-FOS和NOS-1的表达

目的:通过免疫组化的方法研究无水酒精阻滞大鼠腹腔神经丛后脊髓和延髓孤束核内CFOS和NOS1的表达。材料和方法:对70只Wistar大鼠实施手术,建立实验动物模型。分5组于术后不同时间取得脊髓和延髓样本,并用标准方法对其进行CFOS和NOS1免疫组化染色,观察脊髓和延髓孤束核CFOS和NOS1的表达。结果:无水酒精阻滞后脊髓后角、延髓孤束核神经元细胞内均有CFOS和NOS1表达。结论:无水酒精阻滞腹腔神经丛后,短时间内脊髓后角和延髓孤束核内CFOS和NOS1表达阳性,表明FOS和NOS1与内脏信息在脊髓水平的传导有关。CFOS和NOS1参与了内脏信息在孤束核内的传导。     

Diabetes mellitus and open heart surgery

A method, based on bedside determinations of blood glucose by nursing staff, was designed to control the administration of insulin to diabetic patients during and following open heart surgery. A computer-controlled intravenous infusion pump was used to deliver the insulin. Excellent control of the hyperglycaemia normally associated with open heart surgery was achieved, with 84 percent of measured blood glucose values falling within 2 mmol/litre of the target value of 6 mmol/litre. The method proved to be simple, effective, and safe.     

Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP)

Heparin-induced Extracorporeal LDL-Precipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen. In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range less than 5%) was observed. Long-term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibialis anterior in five patients before and after a single HELP treatment increased from 30 +/- 4 to 37 +/- 7 mmHg and from 27 +/- 2 to 31 +/- 3 mmHg respectively. These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.     

尿毒症时阴离子隙的影响因素

本文报告64例曾作过血电解质检查及血气分析的尿毒症患者。旨在推定尿毒症时阴离子隙(AG)的影响因素及临床意义。血Na~+及血Cl~-浓度可影响AG(P<0.01)、AG降低常伴血Cl~-浓度异常(P<0.01),血HCO_3~-浓度和AG值关系不大(P<0.05),酸中毒程度和AG数值之间无对应关系(P>0.05)。认为AG是确定尿毒症酸中毒很有用的参数,但由于受许多因素影响,应用时务须注意。