Ethanol potentiation of central nervous system trauma

Two models have been used to study the effects of ethanol on injuries of the central nervous system. The spinal cords of cats were injured by delivering a 200 gm-cm impact to the exposed dura mater. A second group of animals received a similar injury to the exposed dura mater overlying the cerebral hemispheres. The animals were divided into two groups, those that received an infusion of ethanol before injury, and control animals that received no ethanol. The parameters of injury used in this model produced small and insignificant lesions in those animals that received no ethanol; however, when the animals were pretreated with ethanol, a considerable increase in the extent of the injury was noted. These include alterations in membranes-bound enzymes and clotting mechanisms, and alteration of cell membranes through abnormal free radical reactions.     

Early prostaglandin release from the ischemic myocardium in the dog

Cellular consequences of myocardial ischemia were studied in anesthetized dogs. Confirmation of myocardial ischemia was provided by electrocardiographic and biochemical indexes. Prostaglandin F2alpha release into coronary venous blood was significantly elevated during myocardial ischemia, whereas indomethacin treatment prevented this increase in coronary venous prostaglandin F2alpha concentrations. No significant increase in prostaglandin E2 release was observed in response to myocardial ischemia, but indomethacin treatment significantly reduced coronary venous prostaglandin E2 concentrations below those of control values. Within one hour after occlusion of the coronary artery, the S-T segment was significantly altered, and coronary venous prostaglandin F2alpha had increased significantly above the control concentration. These changes persisted during four hours of myocardial ischemia. Plasma creatine phosphokinase activity increased significantly after two hours of myocardial ischemia and remained elevated for the subsequent two hours of ischemia. After four hours of myocardial ischemia, myocardial creatine phosphokinase activity of ischemic myocardium was significantly reduced, and labilization of myocardial treatment prevented increases in prostaglandin release but did not influence other biochemical changes or the electrocardiographic response to ischemia. Thus, prostaglandin release by ischemic myocardial tissue is an early response to the ischemic stimulus.     

Preload assessment in patients with an open abdomen

Health care providers and purchasers of health services have an opportunity to improve patient care and potentially save costs through the wise purchase of interactive health communication applications for patients and employees. Purchasing decisions based on evaluation and evidence should drive the design and development of new systems. The cycle of evaluation includes a needs assessment before system development, usability testing during development, and studies of use and outcomes in natural settings. This type of evidence is critical to our understanding of how best to provide health information and decision assistance to patients, employees, and others.     

Purification and partial characterization of candidate antidiuretic hormone water channel proteins of M(r) 55,000 and 53,000 from toad urinary bladder

Antidiuretic hormone (ADH) increases toad bladder granular cell apical membrane osmotic water permeability (Pf) by insertion of cytoplasmic vesicles containing water channels into the apical membrane. Termination of ADH stimulation results in endocytosis of water channel-containing membrane. In previous work, we have purified water channel-containing vesicles and demonstrated that they contain 12 major protein bands when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). On the basis of vectorial labeling studies of granular cells and purified vesicles, we have proposed previously that vesicle proteins of 55, 53, and 17 kDa are ADH water channel components. In this report, we have purified and analyzed these three proteins using a combination of SDS-PAGE, peptide mapping, amino acid composition, and amino-terminal analyses. The 55- and 53-kDa proteins are distinct protein species possessing a high degree of structural similarity. Both possess a large content of cysteine. The 17-kDa protein appears to be a proteolytic fragment of the 53-kDa protein. None of these three proteins is phosphorylated or contains large amounts of covalently linked carbohydrate. ADH-elicited Pf is inhibited by the organic mercurial reagent fluorescein mercuric acetate (FMA). Exposure of water channel-containing vesicles to FMA labels selectively four vesicle proteins of 92, 55, 53, and 29 kDa while reducing vesicle Pf by 82%. The combination of FMA and 2-mercaptoethanol or exposure to another mercurial reagent, n-ethylmaleimide, does not inhibit vesicle Pf. Together, these data provide additional evidence for the role of the 55- and 53-kDa proteins as components of the ADH water channel. These candidate ADH water channel proteins are distinct from a 28-kDa candidate water channel protein (CHIP 28) isolated recently from human erythrocyte membranes and kidney proximal tubule by Agre and co-workers (Preston, G. M., Carroll, T. P., Guggino, W. B., and Agre, P. (1992) Science 256, 385-387).     

Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE)

BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS and RESULTS: Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS: Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.     

An audit of magnetic resonance imaging in the paediatric orthopaedic setting

AIMS: To determine when magnetic resonance imaging (MRI) is helpful in the management of a selected group of paediatric orthopaedic patients. METHODS: A retrospective analysis of 131 MRI scans was undertaken with allocation into seven categories based on clinical presentation. RESULTS: MRIs performed for spinal, congenital and intra-articular pathology, as well as for growth plate assessment correlated well with subsequent clinical and/or surgical findings. Three of ten MRIs (30%) incorrectly assessed whether a foreign body was present with a sensitivity of 0.60 and specificity of 0.80. Three of 20 MRIs (15%) could not accurately distinguish between oedema/effusion and frank infection. Here sensitivity was 1.00 and specificity was 0.73. MRIs performed for assessment of tumours were accurate with respect to margins and extent. Assessment of pathology with MRI was never the indication for MRI, thus it was not surprising that in four of 27 soft tissue tumours (sensitivity of 0.88 and specificity of 0.63) MRI did not correlate with subsequent histological findings. CONCLUSIONS: MRI plays an important role in the assessment of a wide range of musculo-skeletal pathology. MRI does not, and could not be expected to, replace the need for incisional biopsy for tumour diagnosis. It must be used with caution where tissues have been previously explored for foreign bodies. Interpretation of MRI in musculoskeletal infection must consider its timing in the evolution of the patient's infection.     

Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America

Previous studies have shown that three point mutations in exon 1 and a particular promoter haplotype of the mannan-binding lectin (MBL) gene lead to a dramatic decrease in the serum concentration of MBL. In this study, MBL genotypes and serum concentrations were determined in unrelated individuals in a population from Mozambique (n = 154) and in two native Indian tribes from Argentina (i.e., the Chiriguanos (n = 43) and the Mapuches (n = 25)). In both populations, the MBL concentrations were low compared with those found in Eskimo, Asian, and European populations. In Africans, the low serum concentrations were due to a high allele frequency (0.24) of the codon 57 (C) variant, which resulted in a high frequency of individuals with MBL deficiency (0.06), and were also due to the effect of a relatively high frequency (0.13) of low-producing promoter haplotypes. The low concentrations in the South American populations were primarily due to an extremely high allele frequency of the codon 54 (B) variant in both the Chiriguanos (0.42) and the Mapuches (0.46), resulting in high frequencies of individuals with MBL deficiency (0.14 and 0.16, respectively). In the search for additional genetic variants, we found five new promoter mutations that might help to elucidate the evolution of the MBL gene. Taken together, the results of this study show that different molecular mechanisms are the basis for low MBL levels on the two continents.     

Traumatic brain injury in the developing rat: effects of maturation on Morris water maze acquisition

Previous work has demonstrated that postnatal and adult rats show different physiological responses to lateral fluid percussion (FP) brain injury. Compared to adult animals, the younger rats showed longer apnea and shorter unconsciousness, and sustained hypotension at all injury severities, with higher mortality following severe traumatic brain injury (TBI). To determine if these younger rats exhibit differential cognitive impairments, the Morris water maze (MWM) was used to compare the degree of spatial learning deficits between moderately injured postnatal day 17 (P17), P28, and adult rats, as well as their age-matched controls. Comparisons between shams of different ages showed a maturational time course for MWM acquisition, where adult rats learned the task 34-58% faster than younger age groups. Injured adults showed escape latency deficits throughout the entire training period, took 39% fewer direct paths to the platform during training, took 24% longer to reach criterion performance, and showed poor probe trial performance than adult shams. Injured P28s exhibited escape latency deficits during the first week, with 23% more trials to criterion and 24% fewer direct paths compared to P28 shams. In contrast, injured P17 rats showed no significant difference from age-matched controls in terms of escape latency, number of direct paths taken, or time to criterion performance. This work suggests that, upon surviving the insult, P17 injured rats show remarkable sparing compared to P28 and adult injured animals.