Can the Expanded Disability Status Scale be assessed by telephone?

Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. To validate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19-74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0-9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS < 4.5 (n = 46) and > 4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by +0.5 steps and +1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants.

A need to intensify drug surveillance in Germany.

Despite all its limitations, the spontaneous reporting system still forms the basis for drug safety assessments in the Federal Republic of Germany. Although there have been some promising attempts to standardise the methodology of detecting, analysing and evaluating adverse drug events (ADEs) in certain clinico-pharmacological institutes and psychiatric departments, the approaches have not been integrated and are used only locally. The only exception is the Freiburg Documentation Centre for Severe Skin Diseases, which is attempting comprehensive, country-wide documentation of toxic epidermal necrolysis (Lyell's syndrome) and Stevens-Johnson syndrome. We show that surveillance of 40% of all hospital beds would allow the acquisition of reliable data even on rare and serious AEs which could then be extrapolated in a statistically meaningful way. The medical societies in Germany have traditionally taken a leading role in establishing standards for the preclinical and clinical investigation of new drug compounds. We suggest that they also make it their task to define the framework for an intensified adverse events monitoring system, since it is the patient who ultimately benefits from a quantification of drug therapy risks.

Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany.

Little work has been carried out on the epidemiology of the two serious skin reactions--toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, beta-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs.

Renal actions of calcium channel antagonists.

The actions of L-channel calcium antagonists on the kidney are the result of direct and indirect effects. The direct effects are characterized by vasodilation, especially when the renal vascular resistance was enhanced beforehand. The increase in glomerular filtration rate is small and transient in most of the clinical trials with chronic administration. An important direct effect of calcium channel antagonists on renal function is the increase of sodium and water excretion by a tubular action that occurs in the absence of hemodynamic changes. The mechanism of the tubular effects of calcium channel antagonists is not understood at present. An indirect effect of calcium channel antagonists on the kidney is the inhibition of the aldosterone secretion by the adrenals. A sodium and water loss due to inhibition of tubular reabsorption leads to an increase in renin activity and aldosterone concentration in the plasma as seen typically with diuretics. The dissociation of renin- and aldosterone increase by calcium channel antagonists is a new finding and contributes favorably to the anti-hypertensive efficacy of calcium channel antagonists. In experimental acute renal failure mainly diltiazem and verapamil improved recovery of kidney function. In kidney transplantation, diltiazem reduced posttransplant acute tubular necrosis and improved primary graft function. It remains to be seen whether other calcium channel antagonists have a similar beneficial therapeutic effect in pathological states of renal function.

Effect of cyproterone acetate and its metabolites on the adrenal function in man, rhesus monkey and rat.

The effect of oral administration of 17 alpha-acetoxy-6-chloro-1,2 alpha-methylene-4,6]pregnadiene-3,20-dione (cyproterone acetate, Androcur) on the adrenal function in male hypersexual subjects and in female rhesus monkey was investigated on the basis of cortisol and ACTH levels in serum or plasma and excretion of cortisol and 17-ketosteroids. In addition, cyproterone acetate and its main metabolite alcohol of the main metabolite were characterized for treatment of male hypersexual subjects and female rhesus monkeys did not reveal any signs of adrenal suppression. Cyproterone acetate and its metabolites gave on indication of any appreciable anti-inflammatory effect in the adjuvant edema test in rats. However, there was a general increase in the level of blood glucose and liver glycogen as well as a reduction in body weight and organ weight (spleen, thymus and adrenal) in rats, in which 15 beta-hydroxy cyproterone was slightly more active with the exception of adrenal weight tests. It can be concluded that adult man and rhesus monkey are much less sensitive, is so at all, to some corticosteroid-like activities of cyproterone acetate and its main metabolites than the rat.

[Phagocytosis--a central mechanism in inflammatory reaction (author's transl)]. / Phagozytose--ein zentraler Mechanismus der Entzündungsreaktion.

It is attempted to describe the complex pathogenesis of the inflammatory reaction by analysing the mechanisms of several reactions involved. Phagocytosis is a central phenomenon of host defense mechanisms responding to an invasion of foreign bodies. The induction of secondary reactions following phagocytosis is looked at. Several pathogenetic mechanisms responsible for a switch from acute to chronic inflammation are suggested. Known principles of the autonomous regulation of cell effector functions are discussed in relation to their participation in inflammatory reactions.

[On an improved device for measuring skin tearing strength. Technical description and experimental results obtained from rat skin following therapy with topical corticoids (author's transl)]. / Uber ein verbessertes Zugprüfgerät für den Hautreissversuch. Beschreibung der Technik und Versuchsergebnisse an Hautproben der Ratte nach Behandlung mit topisch wirksamen Corticoiden.

Technical details of an improved method for measuring tensile behaviour of normal and treated rat skin are described. The apparatus has been developed specifically for skin specimens so that the extending force and the adequate strain rate until rupture are designed especially for this purpose. Skin is to be mounted in the jaws of the instrument in horizontal position. Preliminary biological data have been worked out.

[Dermal and systemic side effects of fluocortin butylester. Comparative skin tearing experiments with active principles from commercial preparations]. / Dermale und systemische Nebenwirkungen von Fluocortin-butylester (FCB). Hautreissversuche im Vergleich mit Wirkstoffen aus Handelspräparaten.

Different concentrations of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester FCB, Vaspit) and of clobetasone-17-butyrate, clobetasole-17-propionate and hydrocortisone-17-butyrate have been administered topically in order to investigate dermal and systemic side effects. It could be shown that FCB exhibits by far the least side effects. A specially devised apparatus covering the site of substance application, guaranteed an exclusive dermal absorption. Side effects, therefore, cannot be ascribed to oral ingestion of the drugs.