1,720,992 research outputs found
Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients
No full textThyroid diseases are often associated with psychiatric disorders. The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 %. A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients. Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included. In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed. The proportion of pathologically increased anti-TPO levels in patients with depression was high. Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (chi (2) = 5.5; p = 0.019) different between patients with depression (32.7 %) and patients with schizophrenia (5.3 %). In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 1.2-85.3) when compared with schizophrenia patients. TSH basal level did not differ between patients with depression and patients with schizophrenia. Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression. It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity
Additive therapy with antidepressives for schizophrenic patients - Comparison of two patient collectives in stationary area to different treatment time space
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Memantine pharmacotherapy - A naturalistic study using a population pharmacokinetic approach
No full textBackground and objective: Memantine plasma concentrations show considerable interindividual. variability. High memantine plasma concentrations are associated with the occurrence of neuropsychiatric adverse effects such as confusion. The objective of the present study was, therefore, to investigate the reasons for the observed variability of the pharmacokinetics of memantine in a representative patient population and to explore patient covariates on drug disposition. Subjects: Fifty-six ambulatory Western European patients aged 50-91 years. Methods: This prospective study used a full population pharmacokinetic sampling design. After at least 11 days of continuous memantine intake, the patients provided pharmacokinetic profiles, with six measurements each over a 12-hour period, with a total of 335 serum memantine concentrations. Covariates considered for inclusion in the models were: subject demographic factors (age, total bodyweight, gender), laboratory tests (urinary pH), total daily dose of memantine, memantine formulation type, comedication eliminated via tubular secretion and smoking history. The model development was conducted in three sequential steps. First, an adequate basic structural model was chosen (e.g. a one-, two- or three-compartment pharmacokinetic model). The data were analysed to estimate population pharmacokinetic parameters with the nonlinear mixed-effects model computer program NONMEM. Second, the effects of covariates were investigated on post hoc estimates using multivariate statistics. Third, the covariates with significant effects in the second step were used to build a final covariate pharmacokinetic model, again using NONMEM. Results: A two-compartment model with first-order absorption satisfactorily described memantine pharmacokinetics. In the final regression model, total bodyweight, memantine formulation type (solution vs tablets) and concomitant medication eliminated via tubular secretion were all important determinants of the apparent clearance (CL/F). The final regression model was: CL/F (L/h) = (1.92 + 0.048 center dot BW (kg)) center dot 0.530(FRM) center dot 0.769(CMD) where FRM = 1 for patients receiving memantine solution, otherwise FRM = 0; CMD = 1 for patients receiving a comedication eliminated via tubular secretion, otherwise CMD = 0; and BW is bodyweight. Compared with the basic model, the final population pharmacokinetic model explained 61% of the interindividual variance of the apparent clearance. Conclusions: The population pharmacokinetic model that was developed identified a set of sources of variability in the apparent clearance of memantine, which can be used as a reference in order to optimise memantine therapy in Western European patients
Monitoring of nevus density in children as a method to detect shifts in melanoma risk in the population
No full textBackground. Nevus density in children, a well-known risk factor for malignant melanoma, depends both on constitutional factors and on previous ultraviolet (UV) exposure. Secular trends of childhood UV exposure could thus be indirectly monitored by repeated standardized surveys assessing nevus density in children, such as the "childhood monitoring of nevus density (CMONDE-Study)". Methods. Two complete surveys comprising all children at the time of school enrolment were performed in the city and county of Gottingen, Germany, during the years 1999 and 2000. A total of 4252 children with a median age of 6.25 years were examined as part of the mandatory school enrolment health assessment, and complete data were available for 3881 children. Results. Median nevus density was 5.8/m(2) in the entire study group. The subgroup-specific median increased from "Fitzpatrick skin type" IV to II, but the density was not increased for the type I subgroup. Similarly, nevus density rose with increasing lightness of hair color, but was very low in red-haired individuals. While the number of freckles was also strongly associated with nevus density, the association between iris color and skin reflectance, respectively, was weak. The duration of the additional examination for CMONDE was on average 3-5 min per child. Conclusion. We regard CMONDE as a highly feasible surveillance instrument, which should be implemented as an important addition to regular regional or national health reporting. (C) 2003 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved
Analysis of hippocampal atrophy in alcoholic patients by a Kohonen feature map
No full textWe investigated the correlation of hippocampal volume with homocysteine, folate, vitamin B12 and 136 in alcoholic patients and healthy controls applying a Kohonen feature map (KFM) and conventional statistics. Representation of subjects on the KFM suggested an inverse correlation of hippocampal volume with blood levels of homocysteine and correlation with folate and vitamin B6. In conventional statistical analyses (t-test) reduced folate and increased homocysteine was found in alcoholics compared to healthy controls (p<0.01). In female alcoholics vitamin 136 was reduced significantly (p=0.03). Multiple linear regression analyses showed a significant correlation between average hippocampal volume and homocysteine (p<0.001). KFM proved to be a sensitive tool for visualisation of statistical correlations in data sets even if no further statistical information is available
Differential processing and secretion of A beta peptides and sAPP alpha in human platelets is regulated by thrombin and prostaglandine 2
No full textMetabolic and functional studies of the amyloid precursor protein (APP) in platelets have advanced our understanding of Alzheimer's disease (AD). Here we report that human platelets contain A beta peptides, process and secrete them constitutively. Platelets generate formerly unkown A beta-species by differential processing of APP. Release of A beta peptides were also increased by platelet activation with thrombin, indicating the existence of a regulated exocytotic pathway. We showed that A beta-levels, A beta-processing patterns and A beta-release kinetics were regulated by thrombin. In controls, release of A beta peptide species (A beta 1-40/42 and 1-37/38/39/) continued for more than 4 h, while thrombin activated cells ceased secretion after 1 h at large. Treatment of platelets with prostaglandine 2 slowed this process down. Intracellular A beta peptide concentrations decreased steadily until no peptides could be detected after 20 h (control) or after 4 h (thrombin) in cultured platelets. (C) 2008 Elsevier Inc. All rights reserved.University of Erlangen-Nuremberg (ELAN
Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism
No full textHigher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p = 0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald chi(2) = 4.071, OR = 1.043, 95% CI 1.001-1.086, p < 0.05), which was confirmed by Receiver Operating Curves (AUC = 0.68, 95% CI = 0.57-0.79, p = 0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal
Mernantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons
No full textThe present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR213 were quantified by Western immunoblot analysis. Fxposure to ethanol (50 mM) caused an increase in the levels of NRI (137 +/- 11 % of untreated control, P = 0.009), NR2A (128 +/- 14 %. P 0.022) and N213 (136 +/- 119 %, P = 0.012). Coincubation with memantine (10 mu M) completely blocked the ethanol-induced up-regulation of NR1 (102, 4 %) NR2A (95 +/- 7 %) and NR2B (105 +/- 13 %). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6 %, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence. (c) 2005 Elsevier B.V. All rights reserved
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