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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 181 records · Page 10Linked to original sources
PubMed1998

[Microglia: mechanisms of activation and significance in pathogenesis of neuropsychiatric illnesses].

Microglia are the resident macrophages of the brain. They are the central cellular element to initiate defense mechanisms against destructive environmental influences and to facilitate regenerative processes. No other cell type of the brain is endowed with a comparably comprehensive, immunocompetent machinery like microglia. It encompasses cell proliferation, migration and differentiation into full-blown macrophages able to present antigen and to phagocytose cell debris. Relatively little is known about these stages of microglia activation on the cellular and molecular level, although microglia have been described as a separate cell type of the brain as early as in the 30ies of this century by P.del Rio Hortega. This review summarizes the data that have accumulated until now in this respect and tries to embed them into a clinical framework. Special focus has been given to the role of this cell type in the development and progression of Multiple Sclerosis, HIV-associated dementia and Alzheimer's disease.

AIDS Dementia Complex↗
PubMed1998

[Significance of hepatic cytochrome P450 enzymes for psychopharmacology].

Nearly all psychotropic drugs are metabolized by hepatic cytochrome P450-enzymes. In humans, there are 5 isoenzymes involved in this process. The activity of these enzymes can be modulated by a number of commonly used drugs, yielding potentially hazardous interactions. Most of the recently introduced selective serotonin reuptake inhibitors are potent inhibitors of cytochrome P450 enzymes. Thus, the plasma concentrations of tricyclic antidepressants or clozapine might be elevated into toxic levels. In contrast, carbamazepine induces most of the isoenzymes. This potentiates the elimination of tricyclics and antipsychotics and might cause a serious risk for the recurrence of depressive or psychotic symptoms. Moreover, 5-10% of the population are slow metabolizers of CYP2D6. This group is prone to increased adverse effects of moderately dosed medication. This review systematically points out the reported or predicted pharmacokinetic drug interactions in psychopharmacology focussing on clinical significance.

Cytochrome P-450 Enzyme Inhibitors↗
PubMed1998

[Delirium during oral therapy of herpes zoster with acyclovir. Case report and brief review of central nervous system side-effects of acyclovir].

In differential diagnosis of a delir also adverse effects of medicaments have to be taken into account beside other causes. We report a case of an agitated delir with nocturnal disturbance of consciousness, confusion, restlessness and sleeplessness. This delir existed exclusively during the therapy of a cutaneous herpes zoster with zovirax-pills which can only be explained by a causal connection--after exclusion of other causes. As a so far undescribed predisposition for neurotoxicity of oral therapy with acyclovir signs of vascular encephalopathy were found in the patient's cranial magnetic resonance imaging. The central nervous side effects of acyclovir were summarized shortly.

Acyclovir↗
PubMed1998

Social status and the quality of care for adult people with type I (insulin-dependent) diabetes mellitus--a population-based study.

UNLABELLED: The objective of this study was to assess the degree of diabetes care and education achieved for Type I (insulin-dependent) diabetes mellitus at the community level in relation to social status and to elucidate potential pathways that mediate any social class gradient. A population-based sample of 684 adults with Type I diabetes (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years) in the district of North-Rhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. RESULTS: HbA1c (normal 4.3-6.1%) 8.0 +/- 1.5%, incidence of severe hypoglycaemia (injection of glucose or glucagon) 0.21 cases per patient-year; 62% of patients had participated in a structured group treatment and teaching programme for intensification of insulin therapy; 70% used 3 or more insulin injections per day, 9% were on continuous subcutaneous insulin infusion; 91% reported to have had measurements of HbA1c during the preceding year, and 80% to have had an examination of the retina by an ophthalmologist. Care was insufficient with respect to the quality of blood pressure control (70% of patients on antihypertensive drugs had blood pressure values > or = 160/95 mmHg), patient awareness of proteinuria/albuminuria (27% of patients had not heard about it) and prevention of foot complications (only 42% with a diabetes duration over 10 years had remembered to have a foot examination during the preceding 12 months). There was a pronounced social gradient with respect to micro- and macrovascular complications (prevalence of overt nephropathy 7 vs 20% for highest vs lowest quintiles of social class [OR 3.5, 95% CI 1.6-7.5, p = 0.002]) and diabetes-specific quality of life. HbA1c, blood pressure and smoking accounted for part of the association between social class and microvascular complications. The social class gradient was not due to inequality to access to health services, but to lower acceptance among low social class patients of preventive and health maintaining behaviour. In conclusion, achieved standards of care are high with respect to the implementation of intensified treatment regimens, the level of patient education achieved, treatment control and eye care, whereas areas for improvement are blood pressure control and preventive measures for foot care. A substantial social gradient in diabetes care persists despite equal access of patients to health services.

Adolescent↗
PubMed1998

Risk factors of severe hypoglycaemia in adult patients with Type I diabetes--a prospective population based study.

The objective of this study was to identify possible risk factors of severe hypoglycaemia (SH) in a prospective population based study of adult Type I (insulin-dependent) diabetic patients. A representative sample of 684 patients (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years), living in the district of Northrhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables, hypoglycaemia awareness, diabetes management, and attitudes and behavioural aspects as expressed by the patients. After a mean of 19 +/- 6 months 669 (98%) patients were interviewed about events of SH since the baseline examination. Using the multiple Cox proportional hazards model, five risk factors of SH were identified: SH during the preceding year [hazard ratio (HR) 2.7, 95% confidence intervals (CI) 1.8-4.2], any history of SH (HR 1.9, CI 1.1-3.4), C-peptide negativity (HR 4.0, CI 1.2-12.7), social status (HR 0.8 for a difference of 5 units for a value range of 0-24, CI 0.6-0.9), and patients' determination to reach normoglycaemia (HR 0.7 for a difference of 1 unit for a value range of 1-6, CI 0.5-0.9), indicating that the lower the social status and the higher the patients' determination to reach normoglycaemia, the higher the risk of SH. After eliminating the history of hypoglycaemia from the model, impaired hypoglycaemia awareness and patients' inappropriate denial of SH as their particular problem became additional significant risk factors of SH. In conclusion, in this population based study of adult Type I diabetic patients, C-peptide negativity, a previous event of SH, patients' determination to reach normoglycaemia and social class were risk factors of SH.

Adult↗
PubMed1998

Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation.

This paper attempts to summarize the evidence for the hypothesis that psychostimulant-like neurotransmitter processes within certain regions of the limbic system induce the positive effects of antidepressant sleep deprivation (SD). Preclinical and human studies indicate similar neurobiological effects of psychostimulants such as amphetamines, cocaine and SD. In clinical use, SD and psychostimulants have similar characteristics and behavioral effects. Furthermore, acute psychostimulant challenge decreases limbic metabolism in imaging studies, and SD decreases elevated limbic metabolism in SD responders, indicating that psychostimulant-like neurotransmitter release could decrease limbic metabolism in SD responders. Most antidepressant pharmacotherapies change the reactivity of the dopamine system, and a decrease of presynaptic dopamine or postsynaptic availability can induce depression. Sleep is accompanied by a reduction of catecholamine release and those processes which are increased by psychostimulants. It is concluded that a proposed regional postsynaptic deficit in catecholaminergic neurotransmission can be overcome either acutely by enhanced release during SD or psychostimulant use, or chronically by changes in receptor sensitivity or gene expression due to antidepressant therapies. A postsynaptic deficit in these areas becomes evident if presynaptic release is reduced in conditions such as sleep. Therefore, sleep is depressiogenic for predisposed individuals and the reduction of sleep avoids understimulation of subsensitive postsynaptic processes, which are enhanced by psychostimulants.

Animals↗
PubMed1998

Early-onset Alzheimer's disease due to mutations of the presenilin-1 gene on chromosome 14: a 7-year follow-up of a patient with a mutation at codon 139.

Mutations in the presenilin-1 gene (PS-1 gene) on chromosome 14 have recently been identified as a cause of familial early-onset Alzheimer's disease (EOAD). To our knowledge, only two German EOAD patients with mutations in the PS-1 gene have been identified thus far. Herein we report the case of a German EOAD patient with a family history of dementia and a missense mutation at codon 139 (M139V) of the PS-1 gene. The patient came to our clinic for the first time when he was 44 years old. During the following 7 years, his Mini-Mental State Examination (MMSE) score dropped from 24 to 0. Myocloni were an early neurological symptom that was already present during the first consultation. We could demonstrate that myoclonic activity was of cortical origin using a back-averaging method. Magnetic resonance imaging (MRI) revealed only slight changes in the early stage of the disease. Follow-up MRI studies showed progression of bitemporal ventricular enlargement and progressive frontal and temporal cortical atrophy. Although the majority of EOAD patients belong to the sporadic (non-genetic) type of AD, early-onset dementia, early myocloni and a familial history of AD should direct attention to the possibility of a genetic form of AD.

Adult↗
PubMed1998

Prediction of posttraumatic stress disorder by immediate reactions to trauma: a prospective study in road traffic accident victims.

Road traffic accidents often cause serious physical and psychological sequelae. Specialists of various medical faculties are involved in the treatment of accident victims. Little is known about the factors which might predict psychiatric disorders, e.g. Posttraumatic Stress Disorder (PTSD) after accidents and how psychological problems influence physical treatment. In a prospective study 179 unselected, consecutively admitted road traffic accident victims were assessed a few days after the accident for psychiatric diagnoses, severity of injury and psychopathology. All were inpatients and had to be treated for bone fractures. At 6-months follow-up assessment 152 (85%) of the patients were interviewed again. Of the patients, 18.4% fulfilled the criteria for Posttraumatic Stress Disorder (DSM-III-R) within 6 months after the accident. Patients who developed PTSD were injured more severely and showed more symptoms of anxiety, depression and PTSD a few days after the accident than patients with no psychiatric diagnosis. Patients with PTSD stayed significantly longer in the hospital than the other patients. Multiple regression analysis revealed that the length of hospitalization was due mainly to a diversity of factors such as severity of injury, severity of accident, premorbid personality and psychopathology. Posttraumatic stress disorder is common after road traffic accidents. Patients with PTSD at follow-up can be identified by findings from early assessment. Untreated psychological sequelae such as PTSD cause longer hospitalization and therefore more costs than in non-PTSD patients.

Accidents, Traffic↗
PubMed1998

Molecular biology of microglia cytokine and chemokine receptors and microglial activation.

Activation of brain microglial cells can be subdivided into a number of stages. Early stages likely are proliferation and migration to sites of cell damage. These two stages have been studied exemplarily on the IL-3 receptor beta-subunit and on the CC-chemokine receptor 5 using molecular biological methods. First, IL-3 receptor beta-subunit cDNA has been cloned in full length from rat microglia. Since cultured microglia are already activated to some extent, mRNA of this subunit has been detected in the isolated cells, but was absent in normal rat brain. Lipopolysaccharide (LPS) increased this mRNA in the cultured cells and LPS injected into the circulation of rats induced the mRNA specifically in brain microglia as revealed by in situ hybridizations. Next, we obtained partial cDNAs of receptor-coupled protein tyrosine kinases JAK 1 and JAK 2. These mRNAs were present both in cultured microglia and in rat brain, but were not influenced by LPS. Finally, a full-length cDNA of the rat chemokine receptor 5 has been obtained by PCR methodology. Its mRNA was increased by administration of LPS both in cultured microglia and in vivo. It is expected, that further investigations on these receptors could help to develop improved strategies to combat chronic inflammatory events in the brain.

Animals↗
PubMed1998

Personality in patients with affective disorders and their relatives.

BACKGROUND: In studies of both patients and high-risk subjects, particular patterns of personality have been found to be associated with affective disorders. Neuroticism and features of the melancholic type of personality seem to be risk factors for depression while premorbid features of the manic type of personality predominate in patients with more manic than depressive episodes. While neuroticism prevails in the majority of mental disorders, the 'affective' personality variants appear to be more specifically associated with affective disorders. METHODS: Personality features were investigated in 122 recovered patients with affective disorders, 58 first-degree relatives (high-risk subjects (HR)) and in the respective control groups (n=48; n=29). Patients were subdivided into: unipolar depression (melancholic subtype); bipolar II; bipolar I with more depressive episodes and bipolar I with more manic episodes. Personality measures were based on the Biographical Personality Interview (BPI) and the Munich Personality Test (MPT). RESULTS: The melancholic personality type (BPI) decreased from the unipolar depressives to the mainly manic group, while features of the manic type increased. MPT scores failed to discriminate between subgroups of patients. HR were significantly more introverted and had a stronger orientation towards social norms than controls according to the MPT, and showed a tendency towards the melancholic type according to the BPI. LIMITATIONS: The sizes of some groups or subgroups are relatively small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests and thus to ascertain the robustness of the results. CONCLUSION: Features of the typus melancholicus seem to be a risk factor for depression. The identification of highly predictive risk factors provides an opportunity for the development of prevention programs.

Adult↗
PubMed1998

In situ reverse transcription-polymerase chain reaction. Applications for light and electron microscopy.

Since its discovery in 1986 by Mullis, the polymerase chain reaction (PCR) has been extensively developed by morphologists in order to overcome the main limitation of in situ hybridization, the lack of sensitivity. In situ PCR combines the extreme sensitivity of PCR with the cell-localizing ability of in situ hybridization. The amplification of DNA (PCR) or a cDNA (RT-PCR) in cell or tissue sections has been developed at light and electron microscopic levels. A successful PCR experiment requires the careful optimization of several parameters depending on the tissue (or of cell types), and a compromise must be found between the fixation time, pretreatments and a good preservation of the morphology. Other crucial factors (primer design, concentration in MgCl2, annealing and elongation temperatures during the amplification steps) and their influence on the specificity and sensitivity of in situ PCR or RT-PCR are discussed. The necessity to run appropriate controls, especially to assess the lack of diffusion of the amplified products, is stressed. Current applications and future trends are also presented.

Animals↗
PubMed1998

Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEG in healthy subjects.

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.

Adult↗
PubMed1998

Effects of the atypical antidepressant trimipramine on field potentials in the low Mg2+-model in guinea pig hippocampal slices.

Trimipramine has been classified as an atypical tricyclic antidepressant, because only weak inhibitory effects on serotonin and/or noradrenaline reuptake have been found. Since some antidepressive drugs (e.g. imipramine) and other agents used in the treatment of affective disorders (e.g. carbamazepine) modulate neuronal calcium channels, trimipramine was tested on field potential changes (fp) in the low Mg2+-model of epilepsy which has been shown to be affected by calcium antagonists. Trimipramine reduced the frequency of occurrence of fp in a dose dependent manner (5-100 microM). The threshold concentration of trimipramine which did not decrease the firing rate was approximately 1 microM. Simultaneous application of subthreshold concentrations (2 microM) of the organic calcium antagonist verapamil with trimipramine decreased the firing rate to 37.0+/-22.7% (means+/-SEM, n=7) with respect to baseline values. In contrast, no additive effects of N-methyl-D-aspartate antagonists and trimipramine were observed. In conclusion, the data suggests that the antidepressive effects observed with trimipramine treatment may be due to its inhibitory action on neuronal calcium channels.

2-Amino-5-phosphonovalerate↗
PubMed1998

The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices.

Little is known about the mechanisms of action of kava pyrones which are the pharmacological active compounds of the plant Piper methysticum Forst. We investigated the effects of the synthetic kava pyrone (+/-)-kavain on long-term potentiation (LTP) in the CA1-region of guinea pig hippocampal slices. (+/-)-Kavain reduced the amplitudes of extracellular field potential changes evoked by electrical stimulation in a concentration dependent manner. These effects were reversible. In experiments with LTP no changes were found in the presence of (+/-)-kavain. In conclusion, our findings suggest (+/-)-kavain to be an effective drug in modulating excitatory signals in the hippocampus of guinea pigs. Additionally, no alterations on synaptic plasticity in hippocampal neurons for this kava pyrone can be presumed.

Action Potentials↗
PubMed1998

Correlation between oral drug absorption in humans, and apparent drug permeability in TC-7 cells, a human epithelial intestinal cell line: comparison with the parental Caco-2 cell line.

PURPOSE: To determine and compare the relationship between in vivo oral absorption in humans and the apparent permeability coefficients (Papp) obtained in vitro on two human intestinal epithelial cell lines, the parental Caco-2 and the TC-7 clone. METHODS: Both cell lines were grown for 5-35 days on tissue culture-treated inserts. Cell monolayers were analysed for their morphology by transmission electron micrography, and for their integrity with respect to transepithelial electrical resistance, mannitol and PEG-4000 transport, and cyclosporin efflux. Papp were determined for 20 compounds exhibiting large differences in chemical structure, molecular weight, transport mechanisms, and percentage of absorption in humans. RESULTS: The TC-7 clone exhibits morphological characteristics similar to those of the parental Caco-2 cell line, concerning apical brush border, microvilli, tight junctions and polarisation of the cell line. The TC-7 clone however appeared more homogenous in terms of cell size. Both cell lines achieved a similar monolayer integrity towards mannitol and PEG-4000. Monolayer integrity was achieved earlier for the TC-7 clone, mainly due to its shorter doubling time, i.e. 26 versus 30 hours for parental Caco-2 cells. When using cyclosporin A as a P-glycoprotein substrate, active efflux was lower in the TC-7 clone than in the parental Caco-2 cells. The Papp and mechanisms of transport (paracellular or transcellular routes, passive diffusion and active transport) were determined for 20 drugs. A relationship was established between the in vivo oral absorption in humans and Papp values, allowing to determine a threshold value for Papp of 2 10(-6) cm/sec, above for which a 100% oral absorption could be expected in humans. Both correlation curves obtained with the two cell types, were almost completely superimposable. These studies also confirmed that the dipeptide transporter is underexpressed in both cell lines. CONCLUSIONS: On the basis of morphological parameters, biochemical activity and drug transport characteristics, the TC-7 clone appeared to be a valuable alternative to the use of parental Caco-2 cells for drug absorption studies.

Administration, Oral↗
PubMed1998

Kinetics of hematopoietic progenitor cell release induced by G-CSF-alone in children with solid tumors and leukemias.

The kinetics of peripheral blood progenitor cell (PBPC) release induced by G-CSF-alone at 10 microg/kg/day were monitored daily in 42 children with solid tumors and leukemias. Median 16- and 27-fold enrichment of circulating CD34+ cells and granulocyte-macrophage colony-forming units (CFU-GM) was noted with peak values occurring after the 4th or the 5th G-CSF dose. Individual values of PBCD34+ cell levels in patients with solid tumors were not significantly different after the 4th and after the 5th dose. The day-of-collection PBCD34+ cell concentration was related to the harvested CD34+ cell (P = 0.0001) and CFU-GM numbers (P = 0.0001). No correlations were found between PBPC enrichment and either patient age, body weight, diagnosis or pre-mobilization treatment duration. The median numbers of 1.1 x 10(6) CD34+ cells/kg and 28.1 x 10(4) CFU-GM/kg were derived from one patient's blood volume processed. Nineteen patients received G-CSF-alone primed grafts and had successful engraftment. Our data indicate that in 88% of children a single standard leukapheresis is sufficient to obtain a minimum graft (2 x 10(6) CD34+ cell and/or 10 x 10(4) CGU-GM per kg) whether undertaken after the 4th dose of G-CSF or the 5th.

Adolescent↗
PubMed1998

Abnormal G protein alpha(s) - and alpha(i2)-subunit mRNA expression in bipolar affective disorder.

Disturbances of events associated with intracellular signaling pathways have been suspected of involvement in the development or progression of affective disorders. Often, heterotrimeric G proteins are located at the beginning of these pathways as modulators of extracellular messages. For this reason, messenger RNA expression of three G protein alpha-subunits and of phosphatidylinositol-3 kinase (PI-3 K) regulatory subunit p85 was examined in granulocytes from patients with bipolar or unipolar affective disorder and compared to healthy controls. Messenger RNA expression of the G protein subunit alpha(q) and of p85 was identical in unipolar and bipolar patients and in controls. Furthermore, mRNAs of G protein subunits alpha(s) and alpha(i2) were not different in unipolar patients as compared to healthy controls. Alpha(s) mRNA, however, was markedly increased in bipolar patients. This increase was observed in lithium-treated (more than 12 months) and in unmedicated patients. Elevated levels of alpha(i2) mRNA in unmedicated bipolar patients did not reach statistical significance, whereas mRNA in bipolar patients receiving lithium was significantly above controls. Finally, long-term medication of unipolar patients with lithium had no influence on alpha(i2) mRNA levels. The data reveal elevated mRNA levels of G alpha(s) as a robust feature of bipolar affective disorder. Moreover, despite responsiveness of alpha(i2) gene expression to cAMP-related events, no substantial upregulation of alpha(i2) mRNA was observed in bipolar patients. The lack of alpha(i2) mRNA upregulation, hence, could be an additional abnormality in these patients. Even though lithium was able to reinstate this upregulation, there was no feedback downregulation of alpha(s). This strongly supports the notion of major disturbances of the cAMP signaling system in bipolar illness.

Adult↗