The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Lobar Pulmonary Edema Due to Mitral Regurgitation: Diagnosis by Echocardiography

A bstract One etiology of unilateral lobar pulmonary edema is mitral regurgitation. Echocardiography is able to demonstrate the retrograde flow of blood into the pulmonary veins and allows timely diagnosis and treatment planning. Correction of mitral regurgitation is followed by resolution of the radiographic abnormality.     

Risk factors for spinal surgical-site infections in a community hospital: a case-control study.

OBJECTIVE: To characterize risk factors for surgical-site infection after spinal surgery. DESIGN: A case-control study. SETTING: A 113-bed community hospital. METHOD: From January 1998 through June 2000, the incidence of surgical-site infection in patients undergoing laminectomy, spinal fusion surgery, or both increased at community hospital A. We compared 13 patients who acquired surgical-site infections after laminectomy, spinal fusion surgery, or both with 47 patients who were operated on during the same time period but did not acquire a surgical-site infection. Information collected included demographics, risk factors, personnel involved in the operations, length of hospital stay, and hospital costs. RESULTS: Of 13 case-patients, 9 (69%) were obese, 9 (69%) had spinal compression, 5 (38.5%) had a history of tobacco use, and 4 (31%) had diabetes. Oxacillin-sensitive Staphylococcus aureus (6 of 13; 46%) was the most common organism isolated. Significant risk factors for postoperative spinal surgical-site infection were dural tear during the surgical procedure and the use of glue to cement the dural patch (3 of 13 [23%] vs 1 of 47 [2.1%]; P = .02) and American Society of Anesthesiologists risk class of 3 or more (6 of 13 [46.2%] vs 7 of 47 [15%]; P = .02). Case-patients were more likely to have prolonged length of stay (median, 16 vs 4 days; P< .001). The average excess length of stay was 11 days and the excess cost per case was $12,477. CONCLUSION: Dural tear and the use of glue should be evaluated as potential risk factors for spinal surgical-site infection. Systematic observation for potential lapses in sterile technique and surgical processes that may increase the risk of infection may help prevent spinal surgical-site infection.     

Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment.

We investigated non-rapid eye movement (non-REM) sleep in patients with newly diagnosed Parkinson's disease (PD) who had never previously received dopaminergic medication. There were no significant differences in the conventional sleep parameters between de novo patients with PD and a healthy control group, but the length of stage 1 sleep and the number of awakenings increased significantly upon administration of dopaminergic drugs. Analyzing the quantitative electroencephalogram (EEG), we observed a significant reduction in the low-delta frequency range and a nonsignificant increase in the sigma frequency range in de novo patients with PD. The dopaminergic medication also nonsignificantly reduced the low-delta and sigma frequencies, the latter to the level of the controls. Possible mechanisms that may account for the observed differences are discussed. It is suggested that Parkinson's disease as well as the application of dopaminergic drugs exerts a desynchronizing effect on the sleep EEG that is reflected in a disruption of sleep continuity.     

A three step supercritical process to improve the dissolution rate of eflucimibe.

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.     

Leisure Activities of Individuals With Prader-Willi, Williams, and Down Syndromes

This study extends laboratory-based profiles to participation in leisure activities for persons with three genetic syndromes. Parents of 223 persons with Prader-Willi, Williams, and Down syndromes filled out a newly developed Leisure Activities Questionnaire. Sixteen items loaded onto five distinct factors: social; visual-spatial; visual-strategy; musical; and physical activities. Individuals with Williams syndrome less often participated in visual-spatial activities, those with Prader-Willi syndrome more often performed both visual-spatial and visual-strategy activities, and those with Williams and Down syndromes more often performed musical activities. With increasing chronological ages, all groups increased in their social activities, while those with Williams and Down syndromes decreased in their visual-spatial activities. In both Prader-Willi and Williams syndrome, decreased maladaptive behaviors related to greater amounts of participation in etiology-related activities. Theoretical and practical implications are discussed.     

A complementarity-determining region peptide of an anti-desmosome autoantibody may interact with the desmosomal plaque through molecular mimicry with a cytoplasmic desmoglein 1 sequence

The sera of patients with pemphigus, a group of autoimmune blistering skin diseases, contain autoantibodies directed against components of adhering junctions termed desmosomes. F12, a human monoclonal antibody derived from a pemphigus patient, recognizes an unknown polypeptide of the desmosomal and hemidesmosomal plaques. The third complementarity-determining region of the F12 heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which interact with components of, respectively, the desmosomal and hemidesmosomal plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside the antigen-combining site and thus might be involved in antigen interactions. The GSSG sequence is essential to F12 function, since a peptide containing the VH-CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with specific modifications of the GSSG sequence did not. These data allow us to hypothesize that certain autoantibodies produced during the course of an autoimmune disease can behave as adhesion molecules, through the molecular mimicry of the motif involved in protein/protein adhesion, and to propose a new self-antigen binding mechanism for some autoantibodies.     

Reliability of IL Monarch ion-selective electrode module for sodium, potassium, and chloride measurements

We evaluated the IL Monarch random-access centrifugal analyzer for measurement of Na+, K+, and Cl- by an indirect potentiometric method. For different concentrations of control material, the total precision (CV) ranged between 0.82% and 1.14% for the three electrolytes; linearity was acceptable within a range of 103 to 215 mmol/L for Na+, 1.6-15.25 mmol/L for K+, and 80-173 mmol/L for Cl-. Data correlated well with those by flame photometry for Na+ and K+ and with those by coulometry for Cl-, both for various biological materials--sera, urines, dialysis fluids--and commercial control materials from various producers. Stability of the potentiometric signal was acceptable: daily variations were 0.2 mV for Na+, 0.05 mV for K+, and 0.03 mV for Cl-. Accordingly, we conclude that the system supplies reproducible and accurate results while being easy to use and requiring little maintenance. The use of indirect potentiometry offers results consistent with those obtained with traditional methods, and easily interpretable by clinical staff. However, better information about the actual ion activity in the tested sample for certain pathologies such as hyperlipemia and dysproteinemia could be obtained by methods involving direct potentiometry.