Shunting for syringomyelia in patients with spinal cord injuries: self-reported, long-term effects in 8 patients.

OBJECTIVE: To investigate the long-term effects of shunting on neurologic outcome of syringomyelia, a complication of spinal cord injury (SCI). DESIGN: Retrospective data collection using telephonic survey. SETTING: University based medical center. PARTICIPANTS: Eight of 15 patients who had shunts placed between 1976 and 1999. INTERVENTIONS: Review of clinical records and self-reported telephone interview. MAIN OUTCOMES MEASURES: Initial clinical presentation, recovery after shunt placement, and subsequent neurologic status were recorded. Patients were asked to rate symptomatic improvement after surgery on a 100-point analog scale; they were also asked whether they would have the surgery again. RESULTS: Presenting symptoms were weakness in all 8 patients, pain in 5 patients, and numbness in 5 patients. After shunting, 6 patients had improved strength, all had less pain, and 2 had less numbness. Six patients experienced neurologic decline an average of 2 years after shunt placement, 3 because of shunt failure, 2 from a new syrinx, and 1 from both shunt failure and new syrinx. Two of the 3 patients who underwent second shunt placements for a new syrinx had full neurologic recovery. Six patients said they would repeat the shunting procedure if necessary, 1 was uncertain, and 1 would not. CONCLUSION: Initial improvements noted after shunting provide long-lasting effects, even though many patients may need a second procedure. Less pain and improved strength are more significant than decreased numbness.     

Individualising gentamicin dosage regimens. A comparative review of selected models, data fitting methods and monitoring strategies.

The various components required for individualising clinical drug dosage regimens are reviewed, including a study of 3 types of fitting procedures, 2 types of gentamicin pharmacokinetic model and the utility of D-optimal times for obtaining serum gentamicin concentrations. The combination of the current Bayesian fitting procedure, the kslope pharmacokinetic model [in which the elimination rate constant (kel) can change from dose to dose with changing creatinine clearance] and the explicit measurement of the assay error pattern yielded predictions of future serum gentamicin concentrations which were (a) slightly better than those found using weighted nonlinear least squares; (b) somewhat better than those found with Bayesian fitting and a fixed-kel model; (c) better than those found using the traditional linear regression fitting procedure and a fixed kel model. D-Optimally timed pairs of concentrations also predicted future concentrations at least as well, and more cost effectively.     

几种超短肽的抗抑郁作用

超短肽(overshort peptides,简称OSP)是一类由2～4个氨基酸组成的活性肽,存在于体内,参与多方面的生理、生化或病理过程,其中有些OSP分布于CNS,可能参与情感等高级神经活动的调节。为了探讨OSP可能的药用前景,我们对其中5个OSP进行了抗抑郁作用研究。     

甲基强的松龙对嗅鞘细胞移植治疗受损视网膜神经节细胞的早期保护效应

目的:观察注射甲基强的松龙对嗅鞘细胞移植治疗受损视网膜节细胞的早期保护作用。方法:实验于2005-09/2006-09在北京大学医学部神经解剖实验室完成。实验动物分组:成年雄性SD大白鼠55只随机取出7只为正常对照组,不进行任何实验处理;其余48只为实验组,在手术显微镜下经动物的左侧眶上缘暴露视神经,然后将视神经鞘顺向划开,在距眼球后壁2mm处将视神经剪断。将实验组动物随机分成4组,每组12只:①损伤组。②静脉注射甲基强的松龙组,动物实施术后30min给予一次性尾静脉注射甲基强的松龙注射液(90mg/kg)。③嗅鞘细胞移植组,动物术后移植嗅鞘细胞组织层。④给药后嗅鞘细胞移植组,动物术后30min给予一次性尾静脉注射甲基强的松龙注射液(90mg/kg),然后移植嗅鞘细胞组织层。术后21d麻醉下处死各组大鼠。实验评估:通过视神经逆行荧光标记和蛋白免疫印迹方法观察视网膜神经节细胞存活状况以及热休克蛋白27表达情况。结果:55只SD大鼠均进入结果分析。①视网膜神经节细胞的存活数量:甲基强的松龙静脉注射组高于损伤组[(16.525±9.557),(9.889±5.585)个/视野,P<0.1],给药后嗅鞘细胞移植组明显高于甲基强的松龙静脉注射组和嗅鞘细胞移植组[(28.881±13.660),(16.525±9.557),(13.513±6.840)个/视野,P<0.1,<0.01]。②各组视网膜神经节细胞热休克蛋白27的表达:甲基强的松龙静脉注射组高于损伤组,给药后嗅鞘细胞移植组明显高于甲基强的松龙静脉注射组和嗅鞘细胞移植组。结论:早期注射甲基强的松龙使受损视网膜神经节细胞存活率升高,并使热休克蛋白27表达上调,同时亦表现出了对移植嗅鞘细胞移植治疗受损视网膜神经节细胞的显著保护效应。     

Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response

Interferon (IFN)-gamma-producing CD8+ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8+ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8+ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor alpha (sIL-15Ralpha) to block the host endogenous IL-15. The treatment markedly reduced the ability of the immune animals to control a lethal infection. CD8+ T cell activities in the sIL-15Ralpha-administered mice were severely reduced as determined by IFN-gamma release and target cell lysis assays. The loss of CD8+ T cell immunity due to sIL-15Ralpha treatment was further demonstrated by adoptive transfer experiments. Naive recipients transferred with CD44(hi) activated/memory CD8+ T cells and treated with sIL-15Ralpha failed to resist a lethal T. gondii infection. Moreover, sIL-15Ralpha treatment of the recipients blocked the ability of donor CD44(hi) activated/memory CD8+ T cells to replicate in response to T. gondii challenge. To our knowledge, this is the first demonstration of the important role of host IL-15 in the development of antigen-specific memory CD8+ T cells against an intracellular infection.     

Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion

To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions.     

Alpha-amylase determination with the Reflotron reagent carrier system: use of whole blood, plasma, and serum, and effect of isoenzymes

In the Reflotron Amylase dry-reagent carrier system (Boehringer Mannheim GmbH) a new substrate is used for determining total amylase (EC 3.2.1.1) activity:indolyl-alpha-D-maltoheptaoside. The procedure shows low imprecision (median CV less than 3.2%), and results for sera, plasma, and capillary and venous blood (y) correlate well with those of a conventional alpha-amylase method involving p-nitrophenyl (PNP)-maltoheptaoside substrate (x) (for 209 blood samples: y = 0.981x + 9.7; r = 0.994). Correlation was also excellent with a method involving maltotetraose as substrate (r = 0.987). Attachment of an indoxyl residue rather than a PNP group to the maltoheptaoside did not affect the substrate response to pancreatic or salivary isoenzyme activity. Therefore, the relative proportion of these isoenzymes did not affect the correlation between the Reflotron Amylase reagent carrier and the alpha-amylase PNP-maltoheptaoside method. With a reaction time of less than 3 min, this system is especially suitable for amylase determination in situations where a prompt result is required.