Neurotransmitter modulation of calcium current in rat spinal cord neurons

The modulation of Ca2+ currents by neurotransmitters was studied in freshly dissociated rat spinal cord neurons, using the whole-cell patch-clamp technique. GABA, baclofen, adenosine, ATP, serotonin, norepinephrine, somatostatin, and dynorphin A inhibited the current through Ca2+ channels in a substantial fraction of cells, while substance P, vasoactive intestinal polypeptide, [D-ala2,d-leu5]-enkephalin, cholecystokinin-8 (sulfated), calcitonin gene-related peptide, angiotensin II, neurotensin, vasopressin, and thyrotropin-releasing hormone had no effect. In the case of baclofen, the inhibition is mediated, at least in part, by a GTP-binding protein. Suppression of Ca2+ current by neurotransmitters may represent a mechanism of presynaptic inhibition in the spinal cord.     

Stabilization of proteins against methylene chloride/water interface-induced denaturation and aggregation.

The purpose of this study was to stabilize proteins during the commonly used microencapsulation process of methylene chloride/water emulsification. The model proteins used in this study included bovine serum albumin (BSA), S-carboxymethylated BSA (CM-BSA), reduced-S-carboxymethylated BSA (RCM-BSA), ovalbumin, and lysozyme. Emulsification of a 0.5-mg/ml protein solution in methylene chloride brought about changes in the composition of water-soluble species and interfacial coagulation. As a result, 37.8, 71.8 and 98.7% of ovalbumin, lysozyme and BSA were recovered from the aqueous phase after emulsification, respectively. Experiments with BSA, CM-BSA, and RCM-BSA demonstrated that a free thiol group and/or disulfide bond participated in interfacially induced dimerization and polymerization of proteins. Interfacial reactions that led to the aggregation of ovalbumin and lysozyme were inhibited by adding hydroxypropyl-beta-cyclodextrin or BSA into their aqueous solutions. Moreover, such beneficial effect of the excipients was observed to be concentration dependent. Under our experimental conditions, the recovery of ovalbumin and lysozyme was improved up to 97.7 and 95.6%, respectively. This study substantiated that an adequate formulation could overcome denaturing effects of the methylene chloride/water interface upon a protein of interest to be encapsulated into microspheres.     

Accuracy of fetal echocardiography

The reliability of prenatal ultrasound (US) for the detection of structural heart defects was investigated in a consecutive population of patients referred for prenatal US. Twenty-eight of 49 fetuses (57%) shown to have one or more heart defects with physical examination or autopsy were found to have congenital heart disease with prenatal US. There were 66 cardiac defects in 49 fetuses, 33 of which were entirely or partly identified (50%). Defects correctly diagnosed included hypoplasia of either ventricle, common atrioventricular canal, tetralogy of Fallot, transposition of the great vessels, and Ebstein anomaly. Defects rarely diagnosed correctly included semilunar valve stenosis, total anomalous pulmonary venous drainage, coarctation of the aorta, pulmonic atresia, atrioseptal defect, and ventricular septal defect. Many types of heart defects can be diagnosed accurately with prenatal US in a general population of patients not at high risk for congenital heart disease. Some lesions, however, were difficult to detect.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

Immunoglobulin G subclass responses to cytomegalovirus in seropositive patients after transfusion

The immunoglobulin G subclass responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 26 seropositive surgery patients and 34 transfused seropositive oncology patients. Also included as controls were 18 surgical patients who received no RBCs during surgery. None of the 78 patients studied had IgG2 to CMV before or after transfusion. The absence of a total IgG response to CMV after transfusion could not be attributed to preexisting deficiencies in one or more subclasses, because all 78 patients had similar levels of IgG1, IgG3, and IgG4 to CMV before transfusion. Discriminant analysis was used for statistical evaluation of the combined CMV subclass responses in each patient and the individual subclass responses. Individual patients responded to CMV antigens with an increase in concentration in any of the three subclasses or any combination of the subclasses, excluding IgG2. IgG subclass analysis showed that 10 of 27 patients who did not respond with at least a fourfold total IgG titer rise had a significant increase in IgG subclass antibodies to CMV. Three of 33 patients with at least a fourfold total IgG titer rise lacked a subclass response. These results suggest that the measurement of IgG subclasses may be a sensitive indicator of immune response to CMV.     

The Efficacy of Tranexamic Acid in Total Knee Arthroplasty: A Network Meta-Analysis

Background

A growing body of published research on tranexamic acid (TXA) suggests that it is effective in reducing blood loss and the risk for transfusion in total knee arthroplasty (TKA). The purpose of this network meta-analysis was to evaluate TXA in primary TKA as the basis for the efficacy recommendations of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Medicine on the use of TXA in primary total joint arthroplasty.

Causes, management and morbidity of acute hypoglycaemia in adults requiring hospital admission

In the community, acute hypoglycaemia is commonly caused by therapies for diabetes mellitus or the excessive consumption of alcohol. Although most episodes do not require admission to hospital, little information is available on the causes and outcome of those that do. We retrospectively surveyed adult patients admitted to a large urban teaching hospital with acute hypoglycaemia in a 12-month period, identifying 56 admissions of 51 patients. Forty-one had diabetes mellitus, 33 (80%) of whom were receiving treatment with insulin. The others had hypoglycaemia induced by excessive consumption of alcohol or by deliberate self-poisoning with insulin. A history of psychiatric illness and/or chronic alcoholism was common. Neurological manifestations of hypoglycaemia were the principal reason for admission, observed on 50 occasions (89%), and 11 events (20%) had precipitated convulsions. Although many patients (59%) had received treatment for hypoglycaemia before admission, hypoglycaemia recurred in 16% of patients in hospital. Four patients (7%) died following admission, but in only one case was this the direct result of hypoglycaemia. However, within 15 months of the index hypoglycaemia event, a further six patients (11%) had died, mostly of causes unrelated to hypoglycaemia. Patients who require hospital admission for treatment of hypoglycaemia have a high incidence of neurological manifestations, a high rate of mental illness and other medical disorders, and may represent a high-risk subgroup with a poor long-term prognosis.