Assessment of cardiovascular disease risk in patients with schizophrenia spectrum disorders in German psychiatric hospitals: results of the pharmacoepidemiologic CATS study.

PURPOSE: Patients with severe mental illness are at high risk for metabolic and cardiac disorders. Thus, monitoring of cardiovascular risks is imperative and schedules for screening for lipids, glucose, body mass index (BMI), waist-hip ratio and blood pressure have been developed. We intended to analyze screening for metabolic disorders in German patients with schizophrenia spectrum disorders in routine psychiatric care. METHODS: We included 674 patients with any F2 diagnosis in out- and inpatient settings and analyzed metabolic screening procedures as practiced under conditions of usual care. RESULTS: Except BMI (54 %), all other values were documented only in a minority of patients: waist circumference (23 %), cholesterol (28 %), fasting glucose (19 %), triglycerides (25 %) and blood pressure (37 %). We found evidence for less than perfect quality of blood pressure measures. The group of patients who met the individual metabolic syndrome ATP III criteria was comparable to the US CATIE trial. CONCLUSIONS: We conclude that frequency and quality of metabolic monitoring in German in- and outpatients settings are not in accordance with the respective recommendations. Similar to previous reports we found evidence for a high prevalence of metabolic disturbances in German patients with schizophrenia spectrum disorders.

[Individual risk screening and visualization as a central element of health days through the interactive electronic GloRiA program]. / Individuelles Risikoscreening und Visualisierung als zentrales Element von Gesundheitstagen. Einsatz des interaktiven elektronischen GloRiA-programms.

BACKGROUND: Health days are an established forum for prevention and health promotion for different groups in the general population. Through the use of modular questionnaires "Global Risk Assessment" (GloRiA) on computers (handheld and desktop), the recording of patient data and presentation of the results can be optimized. Possible applications include identification of risk factors, early detection of patients at risk, epidemiology and health services research, promotion of patient adherence by visualizations (e.g. risk scores). Up to 12 different question modules are available (e.g. risk for the occurrence of cardiovascularevents by Framingham score, forfuture riskof diabetes mellitus using FindRisk score, smoking, COPD, pain, comorbidities). METHODS AND RESULTS: During 57 health days in 2010 and 2011, data were collected from 3451 persons (53% women, mean age 59.6 +/- 15.4 years) using GloRiA. The percentage of former smokers was 32.7%, while that of current smokers was 14.7%. The average 10-year risk based on the Framingham score (calculated with 1739 persons) in 53.7% of respondents was at <10%, in 37.0% at 10-20%, and in 9.3% at > 20%. In men risk was higher than in women. Smoking cessation would theoretically reduce the mean 10-year risk from 10.9 +/- 9.2% to 7.4 +/- 6.6%. In 50.5% of participants blood pressure measurement revealed elevated values, and in 10% or 2%, respectively, a moderately high or high 10-year riskof incident diabetes mellitus according to FindRisk. CONCLUSION: The use of GloRiA for the consolidation of health data under the framework of health days provides new and sustained possibilities in early detection of cardiovascular disease. The calculation and visualization of risks and the impact of treatment decisions, e.g. reduction of cardiovascular risk by smoking cessation, were communicated directly to the participants. The individual health report facilitates the diagnostic procedures bya physician.

Susceptibility of retinal ganglion cells to excitotoxicity depends on soma size and retinal eccentricity.

PURPOSE: This study was undertaken to determine if retinal ganglion cell sensitivity to intraocular N-methyl-D-aspartate or kainate injections varied as a function of retinal location (eccentricity) or cell soma size. METHODS: Rat retinal ganglion cells surviving intraocular N-methyl-D-aspartate or intraocular kainate induced lesions were retrogradely labeled with horseradish peroxidase and analyzed using an image analysis system. Control animals were retrogradely labeled after vehicle injection only. Cell counting was performed at 48 sampling points over the entire retina and represented a total area of 1.92 mm2 per retina. RESULTS: Larger cells were more sensitive to kainate than to N-methyl-D-aspartate excitotoxicity; smaller cells more vulnerable to N-methyl-D-aspartate excitotoxicity. Further from the optic nerve, more smaller cells survived kainate administration. After N-methyl-D-aspartate administration, larger cells survived most, noticeably in the central retina. CONCLUSIONS: Our results suggest that loss of retinal ganglion cells after N-methyl-D-aspartate or kainate administration affects distinct populations of retinal ganglion cells, dependent upon soma size and retinal location. The mechanism by which certain classes of cells survive or succumb to such insults has yet to be determined.

The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia.

Haloperidol is the most commonly used antipsychotic drug in the therapy of acute schizophrenia. Clinicians have been using therapeutic drug monitoring in an attempt to improve clinical application of this drug. The scale of interest in this area is emphasised by the large number of studies (about 50) concerning the serum concentration-therapeutic effect relationship (SCTER) of haloperidol, including 35 studies on patients with acute schizophrenia. However, conflicting results concerning the existence and position of a therapeutic window have emerged. This article aims to provide a comprehensive review of the study design of studies in patients with acute schizophrenia before the study data are used for decision-making. For this purpose, a reproducible system for the evaluation of studies in this special area, a so-called total study score (TSS), was developed on an empirical basis. Thus, insufficient study design was found to be a reason for negative results. On the other hand, in spite of a great variability, the majority of studies with good design provided evidence for a significant SCTER: a bisigmoidal dependence of clinical effect on haloperidol serum concentration. The therapeutic effects of haloperidol increase at low concentrations, and the concentration has a maximum effect at about 10 micrograms/L and again decreasing at higher concentrations. The data of 552 patients also fit to this model in a single scatter plot (pseudo-r2 = 0.076, p < 0.001). The position of the therapeutic window was determined at about 5.6 to 16.9 micrograms/L. Patients treated with serum concentrations within this optimal range had a significantly better response compared with outside this range (p < 0.001, Student t-test). Therefore, a quantitative synthesis of all available data by means of effect-size analysis provides a mean effect-size (g) = 0.499 +/- 0.182 (standard deviation) for the comparison of haloperidol-treatment with serum concentrations within versus outside the therapeutic window. Thus, because of this moderate positive effect, serum concentration assay of haloperidol is recommended for patients with acute schizophrenia in a therapeutic drug monitoring programme. The modalities of haloperidol therapeutic drug monitoring in clinical practice are discussed, e.g. patient selection, method and time for serum concentration measurement, influence of premedication and comedication, interpretation of results and dose adjustment. Clinical investigations into this subject should focus on covariates which are responsible for the variability of the SCTER. Serum concentration assay is advised for investigations of nonresponse to exclude patients with pseudo-drug resistance.

Differences between two substrains of AB mice in the opioid system.

Animals from two substrains of AB mice, i.e., ABH/Md and ABG/Md, differ in the occurrence of aggressive behavior. After maturation, male ABH mice regularly exhibited abnormal aggressive behavior making group-housing impossible. In contrast, ABG animals never showed such behavioral patterns. To elucidate the role of opioid mechanisms, we tested the reaction of these animals to morphine in the hot plate test. Moreover, specific DAMGO binding was measured. It was shown that mice from control groups differed significantly in reaction to the thermal stimulus. ABH mice had significantly longer reaction times. With increasing doses of morphine this difference disappeared, suggesting different levels of basal activity in endogenous opioid systems. This is underlined by significantly lower DAMGO binding in aggressive ABH mice. The results suggest that differences in endogenous opioid systems may account for differences in aggressiveness.

[Intercorrelation of psychopathological, morphologic, neurophysiologic an psychometric parameters in schizophrenic patients]. / Interkorrelation psychopathologischer, morphologischer, neurophysiologischer und psychometrischer Parameter bei schizophrenen Patienten.

The present study was designed to determine the intercorrelation between schizophrenic symptoms, brain morphology, electrophysiological and neuropsychological variables. 44 patients, who met ICD-10 criteria for schizophrenic disorder, were included. At baseline, after 3 and 6 weeks BPRS, CGI, psychometric measurements and QEEG/ERP were performed. A CT scan was performed only at the beginning of the study. Data were evaluated by a multivariate test for data with an inherent structure. One of the most interesting findings is a correlation between BPRS total score and theta EEG power at baseline as well as under treatment. In conclusion, the study suggests the usefulness of multimethodological approaches in order to optimise diagnostic procedures in schizophrenia.

[Evaluation of deprivation manifestations of the auditory system in patients with unilateral middle ear deafness before and after surgical therapy]. / Zur Bewertung von Inaktivitätserscheinungen des auditorischen Systems bei Patienten mit einseitiger Mittelohrschwerhörigkeit vor und nach operativer Therapie.

BACKGROUND: This paper will discuss whether long term conductive hearing loss leads to late onset auditory deprivation as described in the literature in patients suffering from bilateral sensorineural hearing loss and fitted with monaural hearing aids. METHOD: The patients were examined using the Freiburg speech test in the undistorted and distorted forms (according to Dieroff 1985), and the pure tone threshold was ascertained for each patient. Thirty-six preoperative und postoperative results after tympanoplasty and stapes surgery were evaluated. Follow-up was performed six weeks and six months postoperatively. Twenty-one test persons with normal hearing were investigated. RESULTS: Comparison showed that the quotient obtained from undistorted and distorted tests is significantly higher in the affected patients. We even observed a highly significant improvement of this quotient, the speech recognition score (according to Bönninghaus/Röser), and the pure tone threshold after surgery. Seventy-eight percent of our patients showed an improved quotient, and 73% attained a normal value. But in only 29% of all cases did we see a symmetrical quotient in both ears in this period of time. In the statistical evaluation, we were unable to demonstrate a correlation between the patient's age at that moment, the age at the beginning of hearing loss, and this echo quotient. There is also no correlation between the absolute and relative change of the echo quotient and the duration of hearing loss. CONCLUSION: It was evident that the distorted Freiburg speech test is a good method to demonstrate the deprivation of the auditory system. We observed the improvement of the distorted Freiburger speech test at postoperative intervals of six weeks and six months. Hearing training should be applied after surgery in an effort to improve the hearing results.

Antiepileptic drugs--their effects on kindled seizures and kindling-induced learning impairments.

Many epileptic patients suffer from cognitive impairments. These impairments may be a consequence of the epileptogenic process and/or antiepileptic medication. Kindling is considered a useful experimental model to investigate drug effects on both the convulsive component of epilepsy and related alterations at the behavioral level. In our experiments, kindling was induced by repeated injections of pentylenetetrazol (PTZ). To test the effect of antiepileptic drugs on kindled seizures and kindling-induced learning deficits we injected ethosuximide, dipropylacetate, and phenobarbital prior to each kindling stimulation or after kindling completion, and tested these animals in a shuttle-box paradigm. Dipropylacetate and phenobarbital suppressed the development of motor seizures and counteracted the learning deficit. Although ethosuximide had a clear effect on kindled seizures, the learning deficit occurred in kindled rats. This suggests that AEDs effects on kindled seizures are not correlated with the elimination of deficits in the field of cognition.

[The effect of valproic acid monotherapy on behavior and cognitive performance of children with idiopathic generalized epilepsy]. / Der Einfluss einer Valproinsäure-Monotherapie auf das Verhalten und die kognitive Leistungsfähigkeit von Kindern mit idiopathischen generalisierten Epilepsien.

Valproic acid (VPA) currently plays an important role in the treatment of several different types of epilepsy. Especially in children and adolescents, VPA is used because of a minimum of adverse effects and generally little impact on cognitive and psychomotor functions. However, reports in the literature regarding the influence of VPA on behavior and cognitive performance and on EEG parameters vary widely. We investigated the effect of VPA monotherapy on behavioral components (attention, concentration, inhibitory control), cognitive efficiency (motor reaction time, learning, retention) and evoked potentials in 19 children aged 6 to 14 years with idiopathic generalized epilepsy and compared the results with those of healthy controls matched for age. In addition, we analyzed the serum levels of VPA and some of the VPA metabolites in all of the children with epilepsy immediately before the psychophysiological assessments. Our results show marked differences between the children with epilepsy and the healthy controls in all types of behavior and cognitive performance assessed. Abnormal behavior (disturbances of attention and concentration, impulsive behavior patterns) and significant changes in evoked potentials appear to be correlated with serum levels of VPA and certain VPA metabolites.

[Idiopathic varus gonarthrosis: diminished nociceptive vs. unchanged somatosensory sensitivity]. / Idiopathische Varusgonarthrose: Verminderte nozizeptive vs. unveränderte somatosensorische Sensibilität.

Neuromuscular control deficits are supposed to contribute to the development of osteoarthritis (OA). Pain measurements were performed to clarify whether nociceptive afferents differ between OA patients and healthy subjects. Thermal pain thresholds were significantly higher in OA subjects as compared to controls, but there was no difference in perceptual thresholds after electrical stimulation. Lateralization, gender, site of OA changes, previous operations, or medication did not affect these findings.

Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex.

Glutamate dehydrogenase is one of the main enzymes involved in the formation and metabolism of the neurotransmitter glutamate. In the present study we investigated the enzyme ultrastructurally in the cerebellar cortex, a region rich in well defined glutamatergic neurons, by pre-embedding immunocytochemical staining (peroxidase-antiperoxidase), as well as by post-embedding immunogold labelling employing a new system for quantitation and for specificity testing under the conditions of the immunocytochemical procedure. A new antiserum against immunologically purified bovine liver glutamate dehydrogenase or antibodies isolated from this by affinity chromatography were used in rats fixed by perfusion with aldehydes. The pre-embedding method displayed peroxidase reaction preferentially in mitochondria of astroglial cells (including the Bergmann glia). Mitochondria of neuronal tissue elements were usually free of peroxidase-reaction product. Extra-mitochondrial staining was not observed. The post-embedding immunogold method was employed to overcome penetration problems and allow semiquantitative analysis of localization and specificity. The highest densities of gold particles were found over the mitochondria in astroglial cell elements (including the Bergmann glia). Mitochondria in cell bodies of Bergmann glia had a lower particle density than those in astrocytic processes. In the latter, analysis of frequency distribution revealed no evidence of a population of mitochondria lacking glutamate dehydrogenase, but suggested the presence of populations with different levels of immunoreactivity. Comparison with the labelling of embedded bovine liver glutamate dehydrogenase indicated that the enzyme constitutes a high proportion (10%) of the total matrix protein of these mitochondria. A weaker but significant labelling was found in oligodendrocytes of the white matter. The labelling of mitochondria in neuronal elements including glutamatergic mossy fibre terminals was of the order of 15% of that in astroglial mitochondria. No difference was detected between glutamatergic neurons (mossy and parallel fibres, granular cells) and non-glutamatergic neurons (Purkinje cells). The particle density over non-mitochondrial areas was very close to background over empty resin. The results, obtained with different methods of tissue and antibody preparation, agree to show that the present form of glutamate dehydrogenase is restricted to mitochondria and preferentially localized in astrocytes.

Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex.

Glutamate dehydrogenase is one of the main enzymes involved in the formation and metabolism of the neurotransmitter glutamate. In the present study we investigated the enzyme ultrastructurally in the cerebellar cortex, a region rich in well defined glutamatergic neurons, by pre-embedding immunocytochemical staining (peroxidase-antiperoxidase), as well as by post-embedding immunogold labelling employing a new system for quantitation and for specificity testing under the conditions of the immunocytochemical procedure. A new antiserum against immunologically purified bovine liver glutamate dehydrogenase or antibodies isolated from this by affinity chromatography were used in rats fixed by perfusion with aldehydes. The pre-embedding method displayed peroxidase reaction preferentially in mitochondria of astroglial cells (including the Bergmann glia). Mitochondria of neuronal tissue elements were usually free of peroxidase-reaction product. Extra-mitochondrial staining was not observed. The post-embedding immunogold method was employed to overcome penetration problems and allow semiquantitative analysis of localization and specificity. The highest densities of gold particles were found over the mitochondria in astroglial cell elements (including the Bergmann glia). Mitochondria in cell bodies of Bergmann glia had a lower particle density than those in astrocytic processes. In the latter, analysis of frequency distribution revealed no evidence of a population of mitochondria lacking glutamate dehydrogenase, but suggested the presence of populations with different levels of immunoreactivity. Comparison with the labelling of embedded bovine liver glutamate dehydrogenase indicated that the enzyme constitutes a high proportion (10%) of the total matrix protein of these mitochondria. A weaker but significant labelling was found in oligodendrocytes of the white matter. The labelling of mitochondria in neuronal elements including glutamatergic mossy fibre terminals was of the order of 15% of that in astroglial mitochondria. No difference was detected between glutamatergic neurons (mossy and parallel fibres, granular cells) and non-glutamatergic neurons (Purkinje cells). The particle density over non-mitochondrial areas was very close to background over empty resin. The results, obtained with different methods of tissue and antibody preparation, agree to show that the present form of glutamate dehydrogenase is restricted to mitochondria and preferentially localized in astrocytes.

Naloxone ameliorates the learning deficit induced by pentylenetetrazol kindling in rats.

Endogenous opioid peptides modulate and regulate processes of central excitability. Furthermore, opioids are thought to interfere with processes of learning and memory storage. In order to study the effects of endogenous opioids on both processes we injected in the course of development of pentylenetetrazol kindling the opiate receptor antagonist naloxone, and tested the animals afterwards in a shuttle-box task. It was found that naloxone pretreatment had dissociative effects. There was no effect on seizure outcome, whereas the learning deficit was ameliorated in the kindled group. The data suggest that endogenous opioid peptides contribute to the learning deficit found in pentylenetetrazol-kindled rats.

Ultrastructural demonstration of NADPH-diaphorase histochemical activity in the supraoptic nucleus of normal and dehydrated rats.

The ultrastructural location of the NADPH-diaphorase, likely to represent the nitric oxide synthase, was studied in the supraoptic nucleus of control and dehydrated rats. The NADPH-diaphorase activity was found in nuclear envelope, inner and outer membranes of mitochondria, Golgi apparatus, and endoplasmic reticulum in both neurons and astrocytes. We observed an increase in the number of stained mitochondria and an increased staining of the endoplasmic membranes in prolonged dehydration stress. Based on available data, the supraoptic NADPH-diaphorase/nitric oxide synthase seems to be involved in adaptative function of the hypothalamic neurosecretory system.