Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.     

Occurrence of multiple antibiotic resistance and R plasmids in Enterobacteriaceae isolated from children in the Sudan

The prevalence of resistance to six commonly-used antimicrobial agents in faecal coliforms from children in Khartoum, Sudan was studied. A relatively high prevalence of resistance was found, ranging from 96% of children with isolates resistant to ampicillin to 70% of children with isolates resistant to chloramphenicol. Seventy-seven percent of children had isolates with high-level resistance to trimethoprim (MIC greater than 1000 micrograms/ml). Twenty-nine different resistance patterns were found. Thirty-nine percent of the children had isolates resistant to all six antibiotics studied, and 80% of children had isolates resistant to at least four. Transfer of resistance to each of the antimicrobials, in varying combinations, was demonstrated, but did not occur for all resistance patterns. Plasmid analysis showed plasmids ranging from 160 MDa to 2.8 MDa and isolates contained from one to five plasmids of different sizes. There were no consistent relationships between resistance pattern and plasmid profile, but multiple resistance transfer was mediated commonly by plasmids with a molecular weight of 62 MDa. The high prevalence of potentially transferable antibiotic resistance in gut commensals of children in the Sudan may be of importance in the management of enteric and other infections requiring antimicrobial treatment.     

Neural substrates of semantic memory.

Semantic memory is described as the storage of knowledge, concepts, and information that is common and relatively consistent across individuals (e.g., memory of what is a cup). These memories are stored in multiple sensorimotor modalities and cognitive systems throughout the brain (e.g., how a cup is held and manipulated, the texture of a cup's surface, its shape, its function, that is related to beverages such as coffee, and so on). Our ability to engage in purposeful interactions with our environment is dependent on the ability to understand the meaning and significance of the objects and actions around us that are stored in semantic memory. Theories of the neural basis of the semantic memory of objects have produced sophisticated models that have incorporated to varying degrees the results of cognitive and neural investigations. The models are grouped into those that are (1) cognitive models, where the neural data are used to reveal dissociations in semantic memory after a brain lesion occurs; (2) models that incorporate both cognitive and neuroanatomical information; and (3) models that use cognitive, neuroanatomic, and neurophysiological data. This review highlights the advances and issues that have emerged from these models and points to future directions that provide opportunities to extend these models. The models of object memory generally describe how category and/or feature representations encode for object memory, and the semantic operations engaged in object processing. The incorporation of data derived from multiple modalities of investigation can lead to detailed neural specifications of semantic memory organization. The addition of neurophysiological data can potentially provide further elaboration of models to include semantic neural mechanisms. Future directions should incorporate available and newly developed techniques to better inform the neural underpinning of semantic memory models.     

主班工作制在泌尿科临床工作中的应用

2006年10月开始上主班，通过近2个月的主班工作及与前两任主班的共同经验交流，探讨泌尿科主班工作制在临床工作中的应用，现介绍如下。