Electrophysiological indices of response inhibition in human polydrug users.

Previous research in ecstasy users suggests impairment of various executive functions. In general, the executive function of response inhibition appears unaffected by ecstasy use. Nonetheless, it remains a possibility that cognitive tasks alone are not sensitive enough to pick up subtle changes in function. The current study sought to investigate behavioural measures of response inhibition and their electrophysiological correlates in drug users. Twenty ecstasy polydrug users, 20 non-ecstasy polydrug users and 20 drug naïve controls were recruited. Participants completed questionnaires about their background drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a Go/NoGo response inhibition task whilst electroencephalography (EEG) measures were recorded. Analysis of variance (ANOVA) revealed that there were no between-group differences on the behavioural measure of response inhibition. Multivariate analysis of variance (MANOVA) revealed no main effect of group across midline electrodes for the P3, N2 and P2 components. Univariate ANOVA revealed significant between-group differences in the P2 component with the ecstasy user group having a significantly higher mean amplitude than drug naïve controls at two midline frontal electrodes: at Fz and significantly higher mean amplitude than both control groups at FCz. The present study provides evidence of atypical early processing in ecstasy users that is suggestive of compensatory mechanisms ameliorating any behavioural differences.

ERP evidence suggests executive dysfunction in ecstasy polydrug users.

BACKGROUND: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. METHOD: Twenty ecstasy-polydrug users, 20 non-ecstasy-polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. RESULTS: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy-polydrug users.

Detection and identification of morphine in urine extracts using thin-layer chromatography and tandem mass spectrometry.

The application of tandem mass spectrometry to the analysis and identification of morphine following thin-layer chromatography is described. FAB-mass spectrometry and mass spectrometry-mass spectrometry were performed following chromatography on silica gel high-performance thin-layer chromatography plates. The successful application of this simple methodology to a urine extract suggests that this approach has practical utility for confirming the identity of abused drugs detected by thin-layer chromatography.

Detection of drug use in a methadone maintenance clinic: sweat patches versus urine testing.

AIMS: To evaluate the novel use of sweat patches in outpatients attending a methadone maintenance clinic. DESIGN: Assessment of inter-patch reliability and validity of patch results compared to urine tests at the start and end of the patch period. Semi-structured questionnaire on patients' opinion of the patches. Randomized cross-over trial comparing illicit drug use during the week that the patch was worn with a control period. SETTING: Methadone maintenance outpatient clinic in a deprived urban area. PARTICIPANTS: Forty-eight patients with a diagnosis of opiate addiction prescribed methadone for a median of 5 years. MEASUREMENTS: Analysis of urine and patch tests by standard methods for methadone, opiates, morphine (heroin metabolite) and benzoylecgonine (cocaine metabolite). FINDINGS: There was good inter-patch reliability between arm and side patches for methadone (all positive), opiates (k = 0.8) and morphine (k = 1.0) but only moderate agreement for benzoylecgonine (k = 0.49). There was good agreement between the sweat patches and urine tests for methadone (all positive), opiates (k = 1.00) and morphine (k = 0.8), but again only moderate agreement for benzoylecgonine (k = 0.50). The patches were well tolerated and the main side effect was minor irritation. The majority of men preferred a urine test while more women preferred a sweat patch. There was no evidence of reduced use of illicit drugs the period that the patch was worn. CONCLUSION: Sweat patches are reliable and give valid results for patients on maintenance methadone. There are few side effects and it is practical to use them in busy outpatient clinics. They are preferred by some patients but there was no evidence that they altered behaviour.

HDL-cholesterol reductions associated with adult growth hormone replacement.

OBJECTIVE: To study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk. PATIENTS: Thirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 +/- 11.8 year; mean +/- SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start. MEASUREMENTS: Fasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)-cholesterol, HDL-subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF-1. LDL-cholesterol was calculated using the Friedewald formula. RESULTS: Compared to placebo, 6 months treatment with hGH therapy resulted in increased IGF-1 (37.6 +/- 4.1 vs. 14.0 +/- 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL-cholesterol concentration from baseline to 6 months (0.97 +/- 0.08 to 0.76 +/- 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo -26 (-340 to 82), median and range, active -4 (-586 to 212) mg/l). There was no change in total cholesterol, LDL-cholesterol, triglycerides or proportion of HDL subfractions. CONCLUSIONS: Treatment with hGH can reduce serum HDL-cholesterol concentrations. Further investigation of this is required.

Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects.

Utilising a combination of m-aminophenyl-borate affinity chromatography and an immunoradiometric assay for apolipoprotein B (apo B), we have developed a specific and highly sensitive (6 ng/ml) procedure for the assay of glycated apo B. We studied 52 diabetic patients, 50 non-diabetic control subjects and 12 patients heterozygous for familial hypercholesterolaemia (FH). Both insulin-dependent and non-insulin dependent diabetics were included in our study. Total apo B in the diabetics (108 +/- 5 mg/dl; mean +/- S.E.M) was increased (controls: 95 +/- 4 mg/dl; P less than 0.05). In the FH group the serum apo B concentration (216 +/- 24 mg/dl) was significantly higher (P less than 0.001) than both the other groups studied. Both the serum glycated apo B concentration (9.3 +/- 0.8 mg/dl versus 4.8 +/- 0.7 mg/dl) and the percentage glycated apo B (7.9 +/- 0.4% compared to 3.9 +/- 0.2%) were significantly higher in the diabetics than in non-diabetic controls (P less than 0.001). A positive correlation was found between the percentage of glycated apo B and glycated haemoglobin (r = 0.65; P less than 0.001) and fasting glucose concentration (r = 0.52; P less than 0.001) in diabetics. The percentage of glycated apo B in FH patients was not significantly different from controls, but the serum concentration of glycated apo B, because of the greatly increased total level of apo B was raised (8.2 +/- 1.4 mg/dl) to a similar extent to that of the diabetics.

Disturbance in sodium regulating hormones in chronic obstructive uropathy.

Serum atrial natriuretic peptide (ANP), plasma renin activity (PRA), angiotensin II (AII) and aldosterone levels have been studied in patients with chronic bilateral ureteric obstruction resulting from high pressure chronic retention of urine (HPCR), both in the obstructed state and during the post-obstructed period. Increased ANP levels observed during chronic obstruction fell rapidly following urinary tract decompression by urethral catheterisation. Serum ANP resurged briefly within 24 h but stabilised thereafter at a lower level. PRA was initially suppressed but rose after catheterisation, the increase lagging behind the changes seen for ANP. Rising levels of AII and aldosterone followed this trend but, unlike PRA, levels were not completely suppressed in the obstructed state. The observed hormonal changes probably reflect homeostatic mechanisms directed to the maintenance of sodium and water balance during obstruction and to limitation of the diuresis following its relief.

HbA1 in assessment of metabolic control in diabetic BB/E rats.

Estimations of HbA1 levels have been used to assess long-term glycaemic control in spontaneously diabetic BB/E rats. The degree of metabolic control achieved by once daily insulin injections and continuous insulin infusion by osmotic minipump was compared. Citrate gel electrophoresis of lysed erythrocytes, previously washed and incubated in 0.9% NaCl, gave accurate HbA1 values without interference from either abnormal Hb variants or labile glycosylation products. Over a 12 week period there was no significant difference in the mean random weekly plasma glucose concentrations between diabetic rats maintained on insulin injections or continuous infusion therapy. The HbA1 values in the injection-treated animals remained unchanged throughout the study period (mean +/- SEM = 5.1 +/- 0.1%). Diabetic rats treated by osmotic minipump showed a steady decline in values over the same period (4.1 +/- 0.1%; p less than 0.001 vs injected rats) but levels remained higher than those recorded in non-diabetic control rats (2.9 +/- 0.01%; p less than 0.001 vs pump-treated rats). These differences in HbA1 were reflected in the plasma glucose values obtained during a 30 h glucose profile performed after six weeks of insulin therapy. Diabetic rats on injection therapy showed considerable diurnal variation in plasma glucose concentration (5.5-11.2 mmol/l; mean 8.9 +/- 0.5) but continuous insulin infusion eliminated the fluctuations giving a significantly lower mean glucose level over the 30 h period (7.3 +/- 0.1 mmol/l; p less than 0.005). HbA1 levels show a poor correlation with random plasma glucose estimations (r = 0.43) but provide a simple and accurate assessment of long-term glycaemic control without the need for multiple 24 h glucose profiles.

The effect of valproate on blood metabolite concentrations in spontaneously diabetic, ketoacidotic, BB/E Wistar rats.

Valproate is an effective anticonvulsant which is rarely associated with hepatotoxicity. It has profound effects on the intermediary metabolism of isolated rat hepatocytes. In this paper the effect of valproate on blood metabolite concentrations in spontaneously diabetic BB/E rats has been studied. Valproate causes a marked fall in blood ketone body concentrations and a smaller fall in blood glucose concentrations following either oral or intraperitoneal administration. Valproate may have a role in the treatment of patients with "brittle" diabetes.

[Spontaneous esophageal perforation (Boerhaave syndrome)]. / Perforación esofágica espontánea (síndrome de Boerhaave).

A review of the literature reveals that the prognosis is unfavorable in the presence of spontaneous rupture of the esophagus, since approximately 50 per cent of the patients die. It is also generally true that the mortality will increase in a direct relationship to the time elapsed between the onset of the clinical syndrome and the arrival at a correct diagnosis and adequate treatment. The author presents a case review of the so-called Boerhaave's Syndrome in which the correct diagnosis was made and surgical treatment instituted within eight hours of onset. He emphasizes the importance of a careful consideration of the clinical and radiologic findings and especially that of mediastinal and subcutaneous emphysema.