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Biomedical subjects

G Eberhard

Publications and source records attributed to G Eberhard.

At least 19 recordsLinked to original sources

Regulation of Gadd45a mRNA expression in vascular smooth muscle under growth and stress conditions.

In order to identify differentially expressed genes under growth conditions, quiescent vascular smooth muscle cells (VSMCs) were stimulated with foetal calf serum (FCS) or platelet-derived growth factor-BB (PDGF-BB) for different time periods. Analysing the gene expression by the differential display (DD) method, we identified the cDNA of the growth arrest and DNA damage inducible gene 45a (Gadd45a, also known as gadd45 and gadd45a). Treatment with FCS or PDGF-BB led to a transient down-regulating of Gadd45a expression during the G0/G1 phase and maximal expression when cells had completed division. We found that expression of p53 and BRCA1 mRNA precedes Gadd45a mRNA expression with a maximal induction in the S phase. As in smooth muscle cells, a similar pattern of the Gadd45a mRNA expression was observed in knockout Gadd45a(-/-) cultured mouse embryonic fibroblasts (MEFs). However, no differences between Gadd45a(+/+) and Gadd45a(-/-) cell lines were observed regarding their kinetics of cell division. These experiments suggest a function of Gadd45a when cells exit the cell cycle rather than when regulating the entry into the S phase.

Animals↗

A multinational study of the relationships between nighttime urinary melatonin production, age, gender, body size, and latitude.

Overnight urines were collected each month for 12-16 months from 321 normal subjects at 19 medical centers in 14 countries distributed on 5 continents at latitudes from 31 01 South to 77 00 North. Mean melatonin concentration was found to negatively correlate with age, weight, and height. When the sexes were considered separately melatonin only correlated with age for female and with age and weight for males. A weak correlation with latitude, but not longitude, was also found.

Adolescent↗

Normative melatonin excretion: a multinational study.

The present study on overnight urinary melatonin was conducted on the most geographically dispersed population to date, over a 1 year period, also covering a broad age range (18-62 years). An inverse relationship between melatonin and age, as well as between melatonin and weight was observed for both genders. Females as a whole, had higher melatonin values than males. Furthermore, the excretion of melatonin exhibited a bimodal distribution, distinguishing two groups of individuals: low and high melatonin excretors. The cut-off point was set at 0.25 nmol/l for ages up to 40 years and at 0.20 nmol/l for subjects above this age. Since melatonin may be involved in several physiological and pathological processes, it could be of importance to detect the type of melatonin excretion that prevails in various conditions, using a simple noninvasive procedure such as the overnight urinary measurement. For that purpose, this large sample could serve as a worldwide reference databank across different ages and locations.

Adolescent↗

A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice.

The purpose of this double-blind, multicenter trial was to compare the efficacy and safety of sertraline (50-150 mg/day) with those of citalopram (20-60 mg/day) in patients with major depression in general practice during 24 weeks of treatment. The patients were assessed using the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales. Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale. Altogether 400 patients were randomized into the study. A total of 308 patients completed the 24-week study in accordance with the protocol. A significant reduction in the total Montgomery-Asberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks, with no statistically significant differences between the drugs. In the intention to treat-last observation carried forward analysis 76% responded to treatment in the sertraline and 81% in the citalopram group. The final mean doses were 82 mg/day (64% higher than baseline) in the sertraline group and 34 mg/day (70% higher than baseline) in the citalopram group. The response rate in completers in accordance with protocol was 90% in the sertraline group and 93% in the citalopram group. The side-effects were those usually seen, and both sertraline and citalopram were considered to be well tolerated. It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram. With regard to efficacy, no statistically significant differences were found between the drugs.

1-Naphthylamine↗

A chip card for patients with diabetes.

DIABCARD provides the specification for the core of a Chip Card Based Medical Information System (CCMIS) for the treatment of patients with chronic diseases. It will provide an instrument for assessing health care services, improve the links between health care providers and set up communication between the different levels of health care. It will therefore improve the quality of care and thus the life of patients with chronic diseases. DIABCARD concentrates on diabetes at the moment, the concept of the diabetes chip card will, however, be extendable to other chronic diseases.

Chronic Disease↗

[3H]imipramine binding in idiopathic pain syndromes. Basal values and changes after treatment with antidepressants.

The binding affinity (Bmax, Kd) of [3H]imipramine to platelet membranes was investigated in 43 patients with a diagnosis of idiopathic pain syndrome. Measurements were carried out prior to and after 6 weeks' treatment with the antidepressants clomipramine or maprotiline (randomized double-blind trial). Before treatment the Bmax was 11% lower (1109 +/- 237 fmol/mg protein) compared to historical control subjects (n = 21, 1240 +/- 390) and comparable to patients with psychogenic pain with affective symptoms (n = 62, 1110 +/- 360) previously measured at the same laboratory. The Kd was 0.5 +/- 0.3 nM comparable to the Kd of the controls (0.6 +/- 0.2). After 6 weeks of treatment the clomipramine group (n = 11) had significantly lower Bmax = 208.5 +/- 286 (P less than 0.001). In the maprotiline-treated patients (n = 18) the Bmax values (1221 +/- 258) tended to increase towards the values of the controls but without statistical significance. No significant statistical correlation was found between initial Bmax values and clinical outcome.

Antidepressive Agents↗

An educational program on depressive disorders for general practitioners on Gotland: background and evaluation.

General practitioners are the psychiatrists' most important coworkers in the treatment of depressive disorders. A high degree of knowledge about this illness in this group of doctors is of decisive importance. However, the value of postgraduate educational programs for general practitioners has been questioned. The Swedish Committee for the Prevention and Treatment of Depression (PTD) offered an educational program on symptoms, etiology, diagnosis, prevention and treatment of depression to all general practitioners on the Swedish island of Gotland. Lectures on suicide, depressive illness in childhood and in old age and psychotherapy of depressive states were also given. In several control periods data were collected on suicides, referrals to the local psychiatric department, emergency admissions, the quantity of sick leave used and the quantity of inpatient care due to depression. Even the prescription of psychopharmacological drugs on the island was investigated. Overall, the results indicated that general practitioners gratefully accepted the educational program and achieved increasing competence and stringency in treating and preventing depressive states. The program was associated with decreases in the use of psychiatric inpatient care and the sick leave frequency of depressed patients. The possibility of preventing suicides was positively influenced.

Curriculum↗

A double-blind randomized study of clomipramine versus maprotiline in patients with idiopathic pain syndromes.

Seventy patients with idiopathic syndromes were treated with maprotiline, a noradrenaline reuptake inhibitor, or clomipramine, a serotonin reuptake inhibitor in a 6-week, double-blind, randomized, multicenter trial. Fifty-two patients completed the double-blind phase. Overall, 50% of the patients improved. Significant decreases were seen not only in the levels of pain but also in bodily discomfort, sadness an inner tension (determined by visual analogue scales, VAS). A decrease was also found in the frequency of sleep disturbances, intellectual and emotional inhibition, irritability, guilt feelings, retardation, sadness and suicidal ideas (observed ratings). Sixty-three percent of the subjects showed an overall improvement during treatment with clomipramine as compared to 36% during treatment with maprotiline (p less than 0.05). During clomipramine treatment significant decreases were seen on all the six VAS: sadness, bodily discomfort, inner tension, concentration difficulties, memory disturbances and pain. Bodily discomfort and pain were significantly reduced during maprotiline treatment. The effects produced by clomipramine were also significantly greater than the effects caused by maprotiline as concerns psychic anxiety and inhibition (VAS). The overall reduction in VAS was significantly greater with clomipramine when compared to maprotiline. The most important side effects were dry mouth (both drugs) and sweating (clomipramine). However, in the clomipramine group, 8 patients were excluded due to side effects as compared to 1 patient in the maprotiline group. Thus, the results indicate that antidepressants reduce not only pain but are also of clinical value in the treatment of patients with idiopathic pain syndromes. Drugs with pronounced effects on the serotonin reuptake are to be preferred.

Adult↗

[Studies on the biological function of the nucleotide base of vitamin B12].

Studies on the coenzyme activity of some nucleotide base analogues of adenosylcobalamine in the dioldehydratase and methyl-malonyl-CoA mutase systems resulted in fundamental differences: Contrary to dioldehydratase the coenzyme activity remains in the methyl-malonyl-CoA mutase system when adenosyl-cobamides with a strongly modified nucleotide base are studied. The analogues give a good growth response with Escherichia coli. In the growth test with Lactobacillus leichmanii only the cobamides that do not have substituted nucleotide bases in the positions 2 or 3 of their imidazole ring are active.

Escherichia coli↗

Plasma prostaglandin E2 metabolite--measured as 11-deoxy-15-keto-13,14-dihydro-11 beta,16 xi-cyclo-PGE2--in twins with schizophrenic disorder.

Blood samples were obtained from 18 twin pairs, and the major prostaglandin E2 (PGE2) plasma metabolite 15-keto-13,14-dihydro-PGE2 was measured by RIA after its conversion to 11-deoxy-15-keto-13,14-dihydro-11 beta,16 xi-cyclo-PGE2. Significant positive correlations were found in all the twin pairs, in 11 pairs diagnosed as DSM-III schizophrenic disorder and schizoid/schizotypal personality disorder, and in the 5 nonschizophrenic pairs. These results indicate that synthesis of prostaglandins (PGs) is in part genetically determined. With regard to absolute PGE2 metabolite levels, the data did not support the hypothesis of increased PGE2 in schizophrenia. Thus, seven of eight schizophrenic probands had lower metabolite concentrations than their healthy twin siblings, and in one pair they were similar. Furthermore, schizophrenic probands and their healthy sibling controls, taken as a group, had lower PGE2 metabolite levels than the group comprised of affective disorder probands and their respective controls. These findings raise the possibility that a change in PGE2 may be associated with schizophrenic and also possibly with affective disorders.

Alcoholism↗

Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.

Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals.

Adult↗

Psychoses in twins - a longitudinal study. Introductory clinical report.

A sample of psychotic and prepsychotic twins is presented, based on 9000 patients born during 1930--1946 and admitted to psychiatric departments in Scania, Sweden, during the 1960's. All twins of the same sex (76 pairs) were registered and their records examined. Twenty-three complete pairs, where one or both twins showed psychotic or prepsychotic symptoms, were carefully examined with regard to different clinical, genetic, biochemical, and psychophysiological parameters. A fairly young sample was chosen in order to include a sufficient number of discordant pairs to be followed prospectively and thus making it possible to study a group of individuals exposed to a very high risk of developing psychoses. Of the 23 pairs, eight pairs were monozygotic, which is somewhat less than expected and may be due to the very careful diagnoses of zygosity which also included analysis of HL-A antigens. An account is given of material and methods, principles of sampling, and clinical data of all twin pairs. No less than 17 complete pairs were judged to be discordant for serious mental disturbance at the time of the examination. Brief histories of the monozygotic twin pairs are included.

Diseases in Twins↗

Erythrocyte catechol-O-methyltransferase activity in psychotic twins.

Erythrocyte catechol-O-methyltransferase (COMT) activity was analyzed in 20 twin pairs, 6 monozygotic and 14 dizygotic, where one or both twins showed psychotic or prepsychotic symptoms. Fifteen of these pairs, 4 monozygotic and 11 dizygotic, were diagnosed as discordant for serious mental disturbance. The different psychotic states within twins did not seem to be associated with any difference in COMT activity.

Adult↗

Kinetic aspects of monoamine oxidase activity in twins with psychoses.

Monoamine oxidase activity was assayed in platelets from 22 (8 monozygotic and 14 dizygotic) twin pairs. At least one twin of each pair had a serious psychiatric disorder (proband). Phenethylamine was used as substrate and the assay was performed at two different oxygen concentrations (0.06 and 0.12 nM). Apparent Km and Vmax values were estimated from double reciprocal plots. The correlation between proband and control twins was high for both apparent Km (r = 0.83) and Vmax (r = 0.69) when the enzyme was assayed at the higher concentration of oxygen. The monozygotic twins pairs showed very high correlations (Km r = 0.93; Vmax r = 0.86) as compared to dizygotic twins (Km r = 0.81, Vmax r = 0.50) and apparently healthy subjects (Km r = 0.46, Vmax r = 0.33). No difference in kinetic properties was found between schizophrenic and non-schizophrenic twins.

Blood Platelets↗

Schizophrenia susceptibility and HL-A antigen.

The phenotype frequencies of HL-A specificities have been investigated in 47 chronic schizophrenics subdivided in an older and a younger group. The frequency of HL-A 9 was significantly increased in the psychotics as compared to a reference group of 1,263 healthy blood donors, pregnant women and potential kidney donors. Deviations in frequency were also found concerning W 19 and HL-A 5. As HL-A 9 was mainly found in the older group of schizophrenics, it is suggested that HL-A 9 might be associated to some form of schizophrenia with a chronic course.

Adult↗