Operationalization of clinical study objectives: a precondition for demonstrating efficacy.
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Biomedical subjects
Publications and source records attributed to V W Rahlfs.
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Dermal provocation tests with histamine and other mediators of allergy are widely used as diagnostic tools and as clinical pharmacological models. Diurnal variations of skin reactivity e.g. flare reactions have been postulated earlier. Potential differences in skin reactivity using histamine provoked flare areas as model were investigated by means of five different placebo formulations (i.v. solution; p.o. solution; p.o. solid forms). Flare reactions have been provoked every 3rd hour within a time span of 29 h using a cross-over design with an H1-antagonist positive control. No provocation was provided between 0:00 and 7:00 a.m. There was no statistically significant variation of skin reactivity with respect to provocation times under placebo treatment conditions. No dependence on plasmacortisol levels was observed. Interindividual differences in skin reactivity are more pronounced than the intraindividual variations.
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In a double-blind trial of two groups of 50 patients each with irritable colon (of whom 91 could be evaluated) asa foetida was found to be effective at the 1% significance level.
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Data on the segmental spread of analgesia from three independent studies of caudal extradural blocks in children with three different local anaesthetic agents were examined with multiple regression techniques to find the effects of age on dose requirements. All three studies confirmed the existence of a linear relationship between the spread of analgesia and age. As there were no significant differences between the three regression lines a common regression line was calculated. This may be used as a guideline for predicting dose requirements in the daily routine of anaesthesia. By injecting a mixture of a radio-opaque substance and 4% lignocaine it was shown by comparison of the radiological spread of the solution and the distribution of clinical analgesia that the latter always exceeded the former by four to six segments. This may indicate the occurrence of diffusion.
Patients who had undergone orthopaedic surgery were investigated. The changes attributable to premedication and narcosis were characterized by a primary fibrinolysis which was accompanied by a slight hypercoagulability. This increased fibrinolytic activity was more pronounced immediately after the beginning of the operation. The post operative changes are characterized by increased ADP-induced aggregation, increased release of platelet factors 3 and 4 and hypercoagulability with reduced fibrinolysis. The reduction in platelets during the operation could be prevented due to the influence of dextran and hydroxyethyl starch (HES). It came further to a slight increase in the activity of factor VII, to an increased fibrinogen polymerization and also to an increased release of platelet factor 4.
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Design and evaluation of the controlled clinical trial are thoroughly discussed by giving an example for testing a sodium pentosan polysulphate/nicotinic acid combination (Compuron). 60 patients with cerebral vascular disorders were randomly allocated to the two treatments and received medication over a period of eight weeks. A detailed biostatistical analysis of the data led to the following conclusions: 1. Regarding the target symptoms headache, nausea, sleep disturbance, reduced alertness, reduced ability for contacts and moods significant differences in favor of the active medication beginning with the sixth treatment week. 2. Regarding the psychological tests substantial and statistically highly significant (P less than 0.001) therapeutic effects. 3. Statistically significant decrease of the cholesterol and triglycerides level, absolutely as well as relative to placeo medication. 4. No treatment related side effects during the entire trial period of eight weeks.
The effect of Asa foetida (0.1% alcoholic dilution) and a combination of Asa foetida and Nux vomica (0.01% alcoholic dilution) was tested in a multicenter placebo-controlled double-blind trial. Both groups with active medication differed trivially but showed a marked superiority to the placebo group. The differences, however, just miss the conventional 5%-level of statistical significance. For the interpretation of this result it must be considered that only about half of the total of patients could be reached who in the planning phase of the study had been regarded necessary for a statistical confirmation of a therapeutic effect. The diagnosis "Colon irritabile" is discussed in its historical context and the psychological structure of the patient sample is described by means of the scores of a standard personal inventory test (FPI). The trial shows that it is possible to obtain objective results on the basis of the patients' judgment (rating scales with low information content).
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