Anti-S-100 Serum blocks long-term potentiation in the hippocampal slice

S-100 is a calcium-binding, glial protein which has been shown to be involved in behavioral learning and memory tasks. Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy evoked by repetitive afferent stimulation. When anti-S-100 serum is applied by pressure ejection onto the stratum radiatum of area CA1 of the hippocampal slice, the amplitude of the extracellularly recorded population spike is not affected. However, repetitive stimulation of the afferents during S-100 application failed to produce LTP. At a distant site in the same slice, LTP occurs normally. Preimmune normal rabbit serum had no effect on the development of LTP. It appears that S-100 protein is involved in the establishment of LTP.     

Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m² of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.     

Alpha2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women

Summary It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha₂-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white post-menopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P=0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.     

Donor left ventricular hypertrophy increases risk for early graft failure

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25 % of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33 % vs 3 %, P = 0.007). Received: 12 February 1996 Received after resision: 27 June 1997 Accepted: 14 July 1997     

'This isn't very typical I'm afraid': observing community care complaints procedures

The new complaints procedures which local authority social services departments have been required to introduce represent an important mechanism for managing the change of culture associated with recent community care reforms. They also represent a new genre in mechanisms of redress for welfare recipients. This paper reports the findings of a study which has observed considerable diversity in the ways in which local authorities are interpreting the nature and purposes of the new procedures and, in particular, the functions of review panels established under those procedures. Variations in the composition of panels, in the style of review panel proceedings, in perceptions of the panels' powers, and in the ways that complaints and complainants are constituted are all discussed. Attention is drawn to four competing interpretations of the review panels' role and to the need for these to be clarified and prioritised.