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M Beneke

Publications and source records attributed to M Beneke.

18 recordsLinked to original sources
PubMed2000

Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial.

In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.

Activities of Daily Living↗
PubMed2000

The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia.

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.

Aged↗
PubMed1996

Bc meson lifetime.

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Journal Article↗
PubMed1996

Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.

The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references. Single doses of 100 mg were administered in a randomized complete-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.

Administration, Oral↗
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↗
PubMed1992

Neuroendocrine effects of ipsapirone on the hypothalamic-pituitary adrenal axis: CRF, ACTH and cortisol in healthy volunteers.

The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks. The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5-30 mg per day were given.

Adrenocorticotropic Hormone↗
PubMed1992

"Clinical Global Impressions" (ECDEU): some critical comments.

Following experience with several clinical trials, the semantic, logical, and statistical properties of the Clinical Global Impressions Scale (CGI-ECDEU, 1976; CIPS, 1986) were investigated. It was concluded that the CGI in its present version (a) may induce inconsistent rating behavior, (b) contains redundant information, (c) consists of items which exhibit extremely abnormal distribution properties. Furthermore (d), some of these items are inappropriately constructed or (e) cast some doubts on their significance as measurements. It is suggested that item #1 (seriousness of disease) be used at the beginning of a study only, and that item #2 (global improvement) be used sparingly and as single measurement to express the doctor's general impression. There would seem to be no basis for the judgment of a pure drug effect (item #3). The instruction to measure improvement by comparing the patient's present condition to that at admission to the study cannot be recommended. Poor distribution properties and a presumably restricted significance of change ratings suggest that parametric statistics should not be referred to.

Humans↗
PubMed1990

Ipsapirone: evidence for efficacy in depression.

Sixty-five inpatients of a psychosomatic hospital in the Federal Republic of Germany with the diagnosis of anxiety neurosis (n = 31) or neurotic depression (n = 34) as defined by the International Classification of Disease (ICD-9), were randomized to a 4-week course of ipsapirone at 7.5 mg t.i.d. or placebo in a prospective, double-blind clinical trial to assess safety, tolerability, and efficacy. This article reports the efficacy results for those patients with the diagnosis of neurotic depression. The primary efficacy variable for patients with neurotic depression was the change from baseline in the Hamilton Rating Scale for Depression (HAM-D) at 4 weeks of treatment. Considering all of the randomized patients with neurotic depression (n = 34, the intent-to-treat population), the mean change from baseline in the HAM-D at Week 4 (observed cases) was -13.13 +/- 6.06 (n = 16) for the ipsapirone group, and -3.19 +/- 5.99 (n = 16) for the placebo group (p less than .001). A parallel analysis of the change from baseline in the Core Depression score of the HAM-D (defined as the sum of items 1, 2, 3, 7, and 8) also showed a significant treatment difference (p less than .01). Results were similar for the intent-to-treat population, last observation carried forward. Safety and tolerability were evaluated for all study patients independent of diagnosis. Treatment-emergent events (n = 65) were reported by 76 percent of patients treated with ipsapirone (n = 33) and by 38 percent of patients treated with placebo (n = 32).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers].

Comparative Bioavailability of Eicosapentaenoic Acid and Docosahexaenoic Acid from Triglycerides, Free Fatty Acids and Ethyl Esters in Volunteers. The bioavailability of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from triglycerides, free fatty acids and ethyl esters was investigated in 8 female volunteers in a randomized triple cross-over trial with baseline control. EPA/DHA was administered in capsules in form of triglycerides (1.68/0.72 g), free fatty acids (1.35/1.065 g) and ethyl esters (1.86/1.27 g). The resulting EPA/DHA plasma levels were determined and evaluated. The mean relative bioavailability of EPA/DHA compared to triglycerides was 186/136% from free fatty acids and 40/48% from ethyl esters. Maximal plasma levels were about 50% higher with free fatty acids and about 50% lower with ethyl esters as compared to triglycerides. The tolerability of the free fatty acids was much worse than that of triglycerides and ethyl esters. The main side effect was eructation.

Adult↗
PubMed1987

Methodological investigations of the Hamilton Anxiety Scale.

In an open field study 4184 outpatients were assessed by 508 independent doctors using the Hamilton Anxiety Scale (HAMA). The results of the raw score distributions and item and factor analyses showed that the HAMA is unsuitable for differential diagnosis and, while showing a satisfactory degree of consistency, has relatively poor resolution. Departing from Hamilton's two-factor solution (1959), comparison of various solution models showed that a three-factor solution yields a stable and clinically useful item classification, which is also very similar to Hamilton's three-factor solution (1969).

Adult↗
PubMedDate not supplied

Nimodipine in subcortical vascular dementia trial.

Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.

Aged↗