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.     

Sutureless bowel anastomosis using Nd:YAG laser

Small bowel anastomoses were performed without sutures by using the Nd:YAG laser to produce welded enterotomies. Optimal energy levels for contact and noncontact laser were determined. Anastomoses produced using five target energy levels between 100 and 500 J were examined. Short-term anastomotic strength of these enterotomies was measured 1 min after the welding. Bursting pressure of the laser welded enterotomies was compared to the bursting pressure of traditional two-layer, inverting, interrupted sutured bowel anastomoses. The overall mean bursting pressure of non-contact-welded enterotomies was 50.6 mmHg. Optimal laser settings determined in this initial phase were then used to produce anastomoses in rabbits which are recovered postoperatively for 1 or 2 weeks in order to examine long-term viability and integrity of the anastomoses. All chronic rabbit preparations recovered without complication. The mean bursting pressure was 200 mmHg, not significantly different from that of uncut bowel or two-layer sutured anastomosis.     

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.     

Noninvasive Intracranial Cerebral Flow Velocity Evaluation in the Emergency Department by Emergency Physicians

Transcranial Doppler (TCD) is an accepted modality for the evaluation of cerebral blood flow velocities. OBJECTIVES: The purpose of this study was to test the feasibility of bedside TCD measurement in the emergency department (ED) with critically ill, intubated patients. METHODS: A prospective convenience sample of patients presenting to a university hospital over a two-month period underwent TCD evaluation of the middle cerebral artery. Intubated patients with head trauma and any patient requiring tracheal intubation were eligible. A 2-MHz Doppler probe was positioned over the temporal bone to acquire blood flow velocities. An emergency medicine resident and research assistant obtained measurements. Continuous TCD tracings were recorded on a video cassette recorder tape for quality assurance review and data collection. Vital signs and therapeutic interventions were also recorded. Flow velocities were measured in cm/s; the peak Resistance Index (RI) was calculated for each patient. RESULTS: A total of 30 patients were enrolled in the study. Adequate tracings were obtained in 25 patients (83%) without a disruption of resuscitation. Tracings could not be obtained in five patients; they were listed as TCD failures. However, in two of these patients, adequate flow velocity tracings were obtained after resuscitation. Four patients were evaluated during tracheal intubation. One patient was monitored successfully during cardiopulmonary resuscitation. The median time required for data acquisition was 1.9 minutes. The mean highest RI for those who expired was 0.84. For those who survived, the mean highest RI was 0.52. The difference of 0.32 was statistically significant (p = 0.04). CONCLUSIONS: Noninvasive blood flow velocity monitoring of the middle cerebral artery using TCD is feasible in the ED when performed at the bedside on intubated patients with traumatic brain injury and others during tracheal intubation and resuscitation.     

Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND: Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE: To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN: A randomized controlled trial. SETTING: Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS: Twenty healthy little pigs, either male or female, weighing 4.5–5.5 kg, were used. Neurotrend-typed multiparameter monitoring system (Diametrics Company, British); CMA/100 micro-injection pump (Carnegie Company, Sweden). METHODS: The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups: the normothermia group (control group, n =10) and moderate hypothermia group (n =10). ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure (MEP), and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of carbon dioxide (PaCO2), HCO3–]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure (CPP, CPP=MAP(ICP), brain tissue partial oxygen pressure (PO2), partial pressure of carbon dioxide (PCO2), HCO3– and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33–35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES: ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS: All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation: In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [(3.31±1.19), (5.33±0.95) kPa, P < 0.05], CCP was higher, brain tissue PCO2 [(12.03±1.73), (10.59±2.01) kPa, P < 0.05], and brain tissue pH value was higher [(7.03±1.63), (9.40±1.30) kPa, P < 0.05], whereas the brain temperature was decreased as compared with that before cooling [(34.9±0.3), (37.2±0.2) ℃, P < 0.05]. ② Results of blood gases analysis in the moderate hypothermia group: There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group (P > 0.05) CONCLUSION: Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.     

眼底动脉硬化与血压、血糖、血脂的多元分析与评估

目的探讨眼底动脉硬化与血压、血脂、血糖的相关性，评估中风危险度。方法对2004年5月至2008年10月就诊的患者335例，作为观察组，并与无症状的健康体检者180例作对照，动态检测眼底动脉硬化、血压、血糖、血脂的异常变化，并做综合量化评估。结果脑血管疾病与眼底动脉硬化、血压、血糖、血脂等因素密切相关。结论眼底动脉硬化、血糖、血脂、血压异常的量化评分，能够预估中风，以便采取预防性治疗。     

血管内皮生长因子在高原脑水肿形成中作用的实验研究

目的:探讨血管内皮生长因子(VEGF)在高原脑水肿形成中的作用。方法:建立大鼠模拟高原模型,应用脑干湿重比率法定量脑水肿情况、应用荧光素钠透过率测定BBB通透性、应用实时荧光定量RT-PCR法检测脑组织VEGF mRNA含量以及应用蛋白印迹法半定量脑组织VEGF含量。结果:大鼠在高原24 h后脑组织含水率明显增高(P<0.05),荧光素钠透过率显著增加(P<0.01);VEGF mRNA转录及其表达显著增高(P<0.001)。结论:VEGF表达在高原脑水肿形成中起重要作用。