Activity-dependent changes in voltage-dependent calcium currents and transmitter release

The use of capillary electrophoresis (CE) for clinically relevant assays is attractive since it often presents many advantages over contemporary methods. The small-diameter tubing that holds the separation medium has led to the development of multicapillary instruments, and simultaneous sample analysis. Furthermore, CE is compatible with a wide range of detectors, including UV-Vis, fluorescence, laser-induced fluorescence, electrochemistry, mass spectrometry, radiometric, and more recently nuclear magnetic resonance, and laser-induced circular dichroism systems. Selection of an appropriate detector can yield highly specific analyte detection with good mass sensitivity. Another attractive feature of CE is the low consumption of sample and reagents. However, it is paradoxical that this advantage also leads to severe limitation, namely poor concentration sensitivity. Often high analyte concentrations are required in order to have injection of sufficient material for detection. In this regard, a series of devices that are broadly termed 'analyte concentrators' have been developed for analyte preconcentration on-line with the CE capillary. These devices have been used primarily for non-specific analyte preconcentration using packing material of the C18 type. Alternatively, the use of very specific antibody-containing cartridges and enzyme-immobilized microreactors have been demonstrated. In the current report, we review the likely impact of the technology of capillary electrophoresis and the role of the CE analyte concentrator-microreactor on the analysis of biomolecules, present on complex matrices, in a clinical laboratory. Specific examples of the direct analysis of physiologically-derived fluids and microdialysates are presented, and a personal view of the future of CE in the clinical environment is given.     

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Arthroscopic reduction and fixation of bony avulsion of the posterior cruciate ligament of the tibia

Bony avulsion fractures of the posterior cruciate ligament of the tibia have commonly been treated by open reduction and internal fixation using the posterior approach. However, this approach, using the prone position, makes it difficult to investigate and treat other combined injuries of the knee joint. We report a case of posterior cruciate ligament avulsion of the tibia that was arthroscopically reduced and firmly fixed with two cannulated screws. The posterior sag was absent after the operation and the result was excellent. By arthroscopy, we got rigid fixation of the avulsed fragment for early rehabilitation, and detection of a concomitant injury was also possible.     

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.     

Alpha 2 mRNA of Na+K+ ATPase is increased in astroctyes of rat hippocampus after treatment with kainic acid

The Na+K+ ATPase (Na+ pump) plays a central role in regulating cation homeostasis and is thought to have an important role in cell proliferation. The multitude of subunit isoforms comprising the functional Na+K+ ATPase has raised the possibility that specific subunit isoform combinations may be involved in different cellular processes. We have investigated the involvement of the specific isoforms in neurons and glia at the site of a CNS lesion. Intracerebroventricular injection of kainic acid was used to induce neuronal cell loss and reactive gliosis in rat hippocampus and levels of Na+K+ ATPase subunit isoform mRNA levels were determined in cells of rat hippocampus using in situ hybridization. alpha 2 mRNA levels increased 35-40% in CA1 and CA3 astrocytes between 1-3 weeks after KA injection with no significant change in other subunit isoform mRNA levels. In addition alpha 3 mRNA levels in CA1 pyramidal neurons were decreased by approx. 35%. Small neurons in the CA1 and CA3 region showed no changes in mRNA levels for any of the Na+K+ ATPase subunit isoforms. These results may indicate a possible role for alpha 2 subunit isoform in the conversion of glial cells from a normal phenotype to the reactive phenotype characteristic in this model of CNS injury.     

Denial of illness in stroke

BACKGROUND: The effects of stroke on classically nondominant hemisphere functions have received less attention than those on the dominant hemisphere, but visuospatial neglect and denial of illness both produce significant morbidity. SUMMARY OF COMMENT: The early literature on denial of illness is discussed and the etiological theories are examined. These are explanations based on deficits of higher mental function, impaired sensory input (especially proprioceptive), an abnormal representation of body image, psychodynamic defense mechanisms, and/or premorbid personality factors. CONCLUSIONS: Denial of illness is an important consequence of stroke. No explanation thus far proposed is entirely satisfactory. The consequences on rehabilitation and strategies for therapy have not been adequately investigated.     

Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice

Time variation of drinking is substantial and has an effect on aggregate estimates of consumption. In this article it is shown that because of a considerable seasonal variation in consumption (+/- 20%) a serious bias in annual consumption estimates can be expected in surveys with a limited time frame. The present study analyzes drinking data collected in the general population of the Netherlands from March 1985 through December 1985 (including Christmas and New Year's Eve). Since it was expected that sensitivity to temporal fluctuations might not be equal for different methods of measurement, several indices of consumption were compared. Although the assessed seasonal effect varies indeed across types of measurement, across male and female subsample and across types of alcoholic beverage, the general tendency is for consumption to be highest in the spring season and lowest in the autumn. Sales figures fluctuate accordingly. It is evident that the risk of biased estimates is larger the shorter the time frame of the survey. Seasonal variation was highest in the frequency domain. Furthermore, exclusion from the time frame of collective holidays, during which people drink more often and more per occasion (viz., Christmas), increases the risk of biased estimates. Even estimates of abstention, but also regular heavy drinking among women, appear to vary considerably over the three seasons in this study. The main conclusion is that results of comparisons of survey data on drinking, particularly those over time, are more or less invalid if the respective time frames of the surveys do not correspond.     

A little less sodium is not without hazard

Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis.