Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder

We investigated the effect of the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30-40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 +/- 3.3%), slowly developing inhibition of [Ca2+]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells.     

Malignant melanoma in the small intestine

A case story of malignant melanoma is presented. The tumour was localised to the jejunum. The symptoms, diagnosis and treatment are described and the pathogenesis is discussed.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Cyclophosphamide and 4-Hydroxycyclophosphamide/aldophosphamide kinetics in patients receiving high-dose cyclophosphamide chemotherapy

Using a recently developed gas chromatography and mass spectrometry method to determine whole-blood cyclophosphamide (CP) and 4-hydroxycyclophosphamide/aldophosphamide (4-HO-CP/AP) concentrations, we investigated their pharmacokinetics in women receiving CP therapy. Patients (n = 18) received one or two courses of CP: (a) a 90-min i.v. infusion (4 g/m2) followed by a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa; or (b) a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa. Whole-blood exposures to CP [area under the whole blood concentration versus time curve (AUCCP)] and 4-HO-CP/AP (AUC4HOCP) between courses 1 and 2 were compared after normalization to dose (g/m2). A nonproportional increase was observed for the AUCCP between the first course [1112 micrometer. h/g/m2 +/- 14% coefficient of variation (CV)] and the second course (1579 micrometer . h/g/m2 +/- 28% CV) (P < 0.001). In contrast, the AUC4HOCP (27 micrometer . h/g/m2 +/- 25% CV) determined for the first course was 29% higher than the AUC4HOCP (21 micrometer . h/g/m2 +/- 26% CV) for the second course (P < 0.01). The interpatient whole-blood exposures to both CP and 4-HO-CP/AP were remarkably consistent in this patient population with percent CVs ranging from 14 to 28%. Because thiotepa (800 mg/m2) was administered simultaneously with CP during the second course of treatment, possible inhibition of CP metabolism by thiotepa was investigated using human liver microsomes in vitro. IC50 values determined for inhibition of CP metabolism in three individual liver donors ranged from 1.0 to 40 micrometer. However, the clinical relevance of this observation has not been established.     

The P300 component of the auditory evoked potential in the posttraumatic vegetative state

The dynamic studies of P300 component of the acoustic evoked potential were conducted in 12 patients in posttraumatic state of the autonomic system. The amplitude and time parameters of P300 were analyzed, its spatial distribution over the cortex, and features of generation. The obtained results were compared with the normative data. Significant changes in P300 in comparison with the normal characteristics were revealed in patients with the absence of conscious mental activity. These changes were maximally expressed when the state of patients was irreversible. In case of patients' outcome from the studied state the amplitude-temporal and topographic response characteristics tended to normalization but did not reach it completely. The obtained results allow us to consider the P300 component as one of the most informative indices in consciousness recovery after severe brain injury.     

Emergence of non-group A streptococcal necrotizing diabetic foot infections

Recently the authors have noted a disturbing trend toward an increased incidence of necrotizing infections caused by non-group A streptococcal species. This article describes the typical clinical course of such an infection. Prompt surgical intervention, coupled with an antibiotic regimen aimed at mitigating exotoxin release, may be both limb- and life-preserving.     

Ion beam and thermally-induced interface reaction between highT c superconductor thin film and metal overlayer

Ion beam and thermally-induced interface reactions between highT _c superconducting thin film of Y₁Ba₂Cu₃O_7−x and metal overlayer of Ag are studied with a view to control the interfacial property of contact resistance. The interface reaction is induced by 100 keV Ar⁺ ion beam with different ion dose values ranging from 5 × 10¹³ to 3×10¹⁴ ions/cm². The YBaCuO film-metal interface is characterized by using the small angle XRD to study the structural properties of the interfacial phases. The electrical property of the interface, specifically contact resistance, has been investigated for different dose values and thermal treatments. Three-probe vs four-probe configuration has been adopted to measure the contact resistance.     

Respiratory pattern and rebreathing in the Mapleson A, C and D breathing systems with spontaneous ventilation. A theory

A theoretical analysis is presented of the Mapleson A, C and D breathing systems when used in spontaneous respiration. The influence of the respiratory pattern is explained diagrammatically. Simple equations are derived, predicting the fresh gas flow required to prevent rebreathing with different respiratory patterns. Further equations allow the degree of rebreathing caused by inadequate fresh gas flow to be quantified. These are used to examine the effects of different respiratory patterns on the efficiency of the three systems. It is demonstrated that the single most important determinant of efficiency is the duration of the expiratory pause. The nature of the inspiratory and expiratory waveforms is less important and the I:E ratio far less important. The analysis suggests that the Mapleson A system will always be the most efficient of the three systems. The Mapleson C system will be efficient if inspiration is long and the expiratory pause is minimal. The Mapleson D system will be efficient if the expiratory pause is sufficiently long.