Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Interaction of triton X-100 on silica: A relationship between surface characteristics and adsorption isotherms

Adsorption of Triton X-100 on various silica substrates has been investigated. A number of solids, including a natural quartz, this quartz washed with HCl acid and subsequently heated at 1273 K; two aerosils and one Kieselgel silicas were studied. These solids exhibit surface areas in the range of 5 to 430 m² g^?1. All the Triton adsorption isotherms display an S-shape at the adsorption temperatures studied (298 and 308 K). It has been found that the pretreatments of natural quartz (by water washing, impurities removed by acid and/or high temperature calcination) affect considerably the amounts of TX-100 adsorbed. Measurements of surface composition have been made by X-ray photoelectron spectroscopy (XPS) with particular emphasis on the presence of impurities and on the number of OH groups at the surface of the samples. The nature of the surface hydroxyl has also been studied by infrared spectroscopy. Furthermore, the specific number of hydroxyl groups on the surface of the silica samples has been determined by thermogravimetric analysis. Finally an attempt to correlate solid surface characteristics with adsorption isotherms has been developed.     

Triple check for antigen specificity of B cells during germinal centre reactions

Somatic hypermutation of the immunoglobulin variable genes during germinal reactions might permit the expansion of B-cell clones with unwanted (e.g. autoreactive) specificity. Here, Ernst Lindhout and colleagues propose three antigen-specific checkpoints that ensure the appropriate antigen specificity of activated B cells is maintained by regulating the activation, selection and further differentiation of B cells.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.     

STRONG METAL-CERAMIC JOINTS

In this paper the technology for joining metals to ceramics is reviewed. The technologies of metal powder sintering, liquid phase joining with activated brazing alloys and with ceramic frit, solid-state joining, friction welding and mechanical fixation are described. In order to put some perspective on the mechanical data given in the literature, some evaluating remarks on mechanical testing are made.     

Intubation conditions: importance of the rate of repetition of the train-of-four

OBJECTIVES: To assess that neuromuscular relaxation onset of the adductor pollicis (AP) is related to neuromuscular stimulation rate. To assess that train-of-four (TOF) at 0.05 Hz is a more accurate indicator of optimal tracheal intubation time and conditions, than TOF at 0.08 Hz. STUDY DESIGN: Prospective, comparative, randomized double-blind study. PATIENTS: Forty adults, physical class ASA 1 or 2, undergoing general anaesthesia with tracheal intubation were allocated to two groups (n = 20) according to the sequence of stimulation of the AP: either TOF at 0.05 Hz (test group) or TOF at 0.08 Hz (control group). METHODS: Induction of anaesthesia was achieved with thiopentone, fentanyl and vecuronium (0.1 mg.kg-1). Neuromuscular monitoring was obtained with force displacement transducers attached to each AP. Tracheal intubation was performed once AP muscular response obtained with TOF at 0.05 Hz for test group and TOF at 0.08 Hz for control group was abolished. Results are expressed as mean +/- SEM. Fisher exact test was used for intubation conditions comparison. Curarization time between groups was compared with unpaired Student's t test (P < 0.05 accepted). RESULTS: TOF with 0.05 Hz stimulation significantly increased curarization time: 217 +/- 7 versus 162 +/- 6 s (P < 0.001). Intubation conditions were excellent in 95% and good in 5% of patients in the study group, compared to 15 and 40% in the control group, respectively (P < 0.01) in 45% of the control group patients coughing at intubation occurred. CONCLUSION: Low stimulation rate (TOF at 0.05 Hz) of AP is a reliable technique to determine the appropriate intubation time for patients paralyzed with vecuronium.