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Biomedical subjects

J Fritze

Publications and source records attributed to J Fritze.

At least 73 records · Page 4Linked to original sources
PubMed1997

The management of coexisting depression in patients with dementia: potential of calcium channel antagonists.

Depression frequently coexists with dementia, although in many cases the depression is not recognized clinically. Depression represents a major additional burden in dementia, not only for the patients but also for families, caregivers, and, economically, society as a whole. However, depression in patients with dementia does respond to treatment, and appropriate therapy can significantly improve the well-being of these patients. Depression in patients with dementia is currently treated with a variety of standard antidepressive agents (tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors), but none is free from significant side effects. Moreover, the use of these drugs is often complicated by a number of age-related factors or effects on the cholinergic neurotransmitter system. Consequently, an antidementia treatment with concomitant antidepressive properties and an acceptable benefit/risk ratio would represent an attractive therapeutic option. The pathogenesis of depression in patients with dementia is not well understood, but may be related to increased intracellular calcium ions in the CNS, the so-called "calcium hypothesis." This hypothesis may explain why some calcium antagonists exert psychotropic effects, including putative antidepressant activity. Animal models and clinical data provide support for the use of calcium channel antagonists for the treatment of depression, with the potential for good tolerability. The latter aspect is especially important for elderly patients with dementia. Although antidepressive effects have been seen with a number of calcium channel antagonists, the dihydropyridine derivative nimodipine shows particular potential for clinical use, perhaps because nimodipine is one of the most lipophilic of these drugs and therefore achieves high concentrations in the CNS, and because of the unique biochemical properties of the dihydropyridine compounds compared with other L type calcium channel blockers. Nimodipine also increases somatostatin levels in CSF, one of the cardinal biochemical deficits in Alzheimer's disease. Data obtained incidentally from the use of nimodipine in the treatment of elderly demented patients clearly demonstrate significant antidepressant activity by the drug in this patient group. Formal clinical evaluation is therefore recommended to establish more clearly the therapeutic benefits offered by nimodipine in patients who suffer from both dementia and depression.

Aged↗
PubMed1997

Glutamatergic dysfunction in catatonia? Successful treatment of three acute akinetic catatonic patients with the NMDA antagonist amantadine.

Therapeutic efficiacy of the NMDA antagonist amantadine is reported in three acute neuroleptic free akinetic catatonic patients. Intravenous infusion of amantadine led to the resolution of catatonic symptoms and considerable reductions of scores in various motor scales (Simpson Angus scale for extrapyramidal side effects (SEPS), the abnormal involuntary movement scale (AIMS), Rogers catatonia and schizophrenia scales). The therapeutic effect of amantadine showed a characteristic temporal pattern with most pronounced effects four to six hours after administration and recurrence of catatonic symptoms by 24 hours later, at least partially. Such a temporal pattern of therapeutic efficacy and decreasing efficacy occurred in all three patients on all days. The results suggest the central importance of glutamatergic dysfunction in catatonic syndrome.

Adult↗
PubMed1996

Additive effects, but no synergistic interaction of stressful life-events and genetic loading in affective disorders.

Life-event research as well as neurobiological findings point to the relevance of adverse stress for the pathogenesis of affective disorders. The well established genetic root might be related to the sensitivity to stress. In concordance, recent studies showed a synergistic interaction between genetic loading and life-events concerning the precipitation of depression, i.e. there might exist a genetic sensitization to the adverse effects of stressors. The present investigation, using information extracted from 877 case records, did not reveal a synergistic interaction concerning the age at onset and the mean frequency and duration of episodes.

Age of Onset↗
PubMed1996

3H-spiperone binding to peripheral mononuclear cells in psychiatric in-patients.

1. There is an ongoing controversy, if increased binding of 3H-spiperone to lymphocytes might discriminate between schizophrenia and other psychiatric diseases or even be a genetic vulnerability marker for schizophrenia, or predict the response to neuroleptic treatment. 2. Some critical methodological details which might contribute to this controversy are described. 3. 3H-spiperone binding was evaluated in 31 patients with schizophrenia, 7 patients with schizoaffective disorder, bipolar type, 6 patients with a manic episode and 6 patients with a depressive episode of bipolar major affective disorder (DSM-III-R criteria), and in 19 healthy subjects. 4. There were no significant differences in characteristic binding parameters (KD, Bmax) between all groups of psychiatric in-patients and in comparison to healthy subjects. Moreover, there was no relation of binding parameters to any of the subtypes of schizopherenia or to the course of illness according to DSM-III-R-criteria. 5. Neuroleptic treatment or clinical response to treatment had no consistent effect on binding parameters intra-individually. 6. In summary, 3H-spiperone binding to lymphocytes failed to differentiate between the diagnostic subgroups (DSM-III-R) and between treatment responders and non-responders in our sample of patients.

Adult↗
PubMed1995

Cholinergic neurotransmission seems not to be involved in depression but possibly in personality.

Concordant with the adrenergic-cholinergic imbalance hypothesis of affective psychosis, there is a cholinergic supersensitivity in depression. Thus, the anticholinergic properties of some antidepressants might contribute to their efficacy. However, in the present double-blind studies (n = 20) with mianserin and viloxazine, respectively, which lack anticholinergic properties, adjunctive treatment with the anticholinergic biperiden versus placebo did not enhance the antidepressive efficacy. Therefore, we hypothesized that cholinergic supersensitivity might be linked to some possibly predisposing dimension of personality. Indeed, in healthy male volunteers (n = 11) the behavioral and cardiovascular sensitivity to physostigmine correlated significantly with "irritability" and "emotional lability" as well as with habitually passive strategies in stress coping. The rise in plasma cortisol and norepinephrine correlated with "retardation"; that of epinephrine with active coping. Thus, the cholinergic supersensitivity in affective psychoses might be linked to a personality dimension like stress sensitivity rather than to the diagnostic category itself.

Acetylcholine↗
PubMed1995

Clinical findings with nimodipine in dementia: test of the calcium hypothesis.

Calcium toxicity seems to be involved in ischemic brain lesions like in vascular dementia and possibly in primary degenerative dementia of Alzheimer's type. The calcium channel blocker nimodipine readily passes the blood-brain barrier and may thus serve as a pharmacologic probe to test the hypothesis of calcium toxicity. Although nimodipine proved to be superior to placebo in a considerable amount of studies in dementia the concept of calcium toxicity cannot be accepted as established. This is due to some methodological flaws in the clinical trials as well as the limited effect size. Moreover, bridging to other findings especially in Alzheimer-type dementia like amyloid deposition and the relationship to apolipoprotein-E isotypes is still far from complete.

Alzheimer Disease↗
PubMed1994

(3H)dipyridamole and (3H)nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: a comparison.

We compared the binding sites of the adenosine transport inhibitors (3H)dipyridamole (DPR) and (3H)nitrobenzylthioinosine (NBI) in human parietal cortex and erythrocytes. In comparison with guinea pig (3H)DPR marked only slightly more binding sites than (3H)NBI with a Bmax of 1080 +/- 29 and 780 +/- 7 fmol/mg protein respectively in parietal cortex and 24288 +/- 2725 and 20875 +/- 1905 fmol/mg protein respectively in erythrocytes. NBI displaced (3H)DPR binding completely from its binding sites at about KD/2 concentrations in parietal cortex as well as erythrocytes with inhibition constants comparable to its dissociation constants. Lineweaver-Burke analysis in erythrocytes indicated a competitive inhibition of (3H)DPR binding by NBI. Pharmacological characterization of (3H)DPR binding sites in human erythrocytes is consistent with their localization on adenosine transporters. These findings provide evidence that as opposed to guinea pig (3H)DPR and (3H)NBI largely label binding sites to the same adenosine transporter in human erythrocytes and parietal cortex.

Adenosine↗
PubMed1994

Postpartum blues: relationship between not-protein bound steroid hormones in plasma and postpartum mood changes.

The relationship between non-bound steroid hormone levels in plasma and the occurrence of postpartum mood changes was investigated in 26 newly delivered mothers throughout the first 5 days postpartum. Studies with saliva samples had reported higher concentrations of 17 beta-estradiol and progesterone on the days of symptoms in women experiencing postpartum blues. As there had been a controversy as to how far saliva concentrations reflect free hormone levels in plasma, free hormone levels of 17 beta-estradiol and progesterone were determined in plasma using ultrafiltration. No significant difference concerning free hormone levels could be found between women with and without postpartum blues.

Affect↗
PubMed1994

Carbamazepine as adjunct or alternative to lithium in the prophylaxis of recurrent affective disorders.

Patients with affective disorder insufficiently responding to prophylactic lithium present a major problem to maintenance pharmacotherapy. The present retrospective study tested the efficacy of carbamazepine in 73 such patients. The patients who were switched from lithium to carbamazepine monotherapy had additional benefit, but not those switched to combined lithium plus carbamazepine. This failure to replicate a number of recent pilot studies showing synergistic effects of lithium and carbamazepine may however have been due to a heterogeneity concerning the combined effects of some negative response predictors, although none of these was significant in itself. Nevertheless, synergism cannot be taken as guaranteed. Prospective controlled trials are needed.

Adult↗
PubMed1994

Correct titration of non-drugs and some other methodological issues.

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

Administration, Oral↗
PubMed1994

Clinical experiences with nimodipine in cerebral ischemia.

Increased intracellular calcium is involved in the death of neurons associated with cerebral ischemia. After extensive experimental work, the calcium antagonist nimodipine has been investigated in several clinical trials in patients with disorders of the cerebral circulation. A short overview on trials in subarachnoid hemorrhage, head injury, ischemic stroke and cerebral resuscitation is given in this paper.

Brain Ischemia↗
PubMed1993

Nimodipine inhibits [3H]nitrobenzylthioinosine binding to the adenosine transporter in human brain.

The inhibition of [3H]nitrobenzylthioinosine ([3H]NBI) binding to human parietal cortex membranes by adenosine transport inhibitors, adenosine receptor agonists and antagonists and dihydropyridines was investigated. While the adenosine transport inhibitors inhibited [3H]NBI binding with Ki values in the low nanomolar range and the adenosine A1 receptor agonist, cyclopentyladenosine, with a Ki in the low micromolar range, no IC50 values could be obtained for the adenosine receptor antagonists at concentrations up to 100,000 nM. Among the dihydropyridines (+)-nimodipine was the most potent with a Ki of 201 +/- 55 nM. Inhibition of adenosine transport thus may contribute to the clinical effects of nimodipine in the central nervous system.

Dihydropyridines↗
PubMed1993

3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects.

3H-spiroperidol binding to peripheral blood mononuclear cells was measured in 28 patients, who fulfilled DSM-III-R-criteria for schizophrenia and 17 healthy subjects. There were no significant differences in characteristic binding parameters (Kd, Bmax) between schizophrenic and healthy subjects. Moreover, there was no relation of binding parameters to any of the subtypes of schizophrenia or to the course of illness according to DSM-III-R-criteria. However, some patients exhibited higher Bmax values without having a unique clinical symptomatology according to known diagnostic criteria. Neuroleptic treatment had no consistent effect on binding parameters intraindividually. Kd and Bmax values were not related to age or gender. In conclusion, despite our previously reported improved methodology, we were not able to corroborate the clinical importance of this "peripheral marker" as a tool for diagnosing schizophrenia or for predicting the response to neuroleptic treatment in our sample of schizophrenic patients.

Adult↗
PubMed1993

A serine to glycine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein: no role in the genetic predisposition to bipolar affective disorder.

Association studies offer a promising tool to investigate the potential role of DNA sequence variation affecting the expression or sequence of proteins in susceptibility to common diseases. We determined the frequency of a DNA polymorphism resulting in a glycine to serine substitution at position 9 in the extracellular N-terminal part of the dopamine D3 receptor protein in a sample of 83 patients suffering from bipolar affective disorder and 100 control subjects. No significant differences between the groups were found. Thus, this substitution, which is the first sequence variation identified in the dopamine D3 receptor gene altering the amino acid sequence of the protein, can be regarded as a protein variant with no major effect on the susceptibility to bipolar affective disorder.

Alleles↗
PubMed1992

Organic schizophrenic syndrome associated with symmetrical basal ganglia sclerosis and XO/XY-mosaic.

Psychopathological alterations associated with symmetrical basal ganglia sclerosis have been well characterized. A preponderance of a so-called organic affective syndrome has been reported (König 1989), but schizophrenic syndromes have also been described, in particular in young patients (Cummings et al 1983). Symmetrical basal ganglia sclerosis may be secondary to ischemia, hypoxia, trauma, intoxications, inflammations, or hyporesp. pseudohypoparathyroidism. Among idiopathic forms sporadic as well as familial ones with dominant and recessive inheritance have been observed (Billard et al 1989).

Adult↗
PubMed1992

3H-spiroperidol binding to human peripheral mononuclear cells: methodological aspects.

3H-spiroperidol binding to lymphocytes has been proposed as a vulnerability marker for schizophrenia. However, the biological significance and even existence of this "binding site" are still in controversy. Therefore, the present study reevaluated methodological details using a filtration binding assay. The results indicated that some well-known, but obviously uncontrolled pitfalls might contribute to this controversy [e.g., unspecific filter binding, which increased in the presence of (+)-butaclamol, or a variable amount of contaminating granulocytes). Moreover, due to an atypically shaped saturation curve, different mathematical methods to analyze the data were used and compared. The present data should help us to understand the biological relevance of this marker, as viewed in different laboratories.

Adult↗