[Quality of life in patients with remitting-relapsing multiple sclerosis in Germany]. / Lebensqualität bei Patienten mit schubförmiger MS in Deutschland.

The concept of health-related quality of life (QoL) includes physical, psychological,and social aspects. This pertains to consequences of chronic diseases and their therapies beyond biological or pharmacological relations. A considerable amount of literature concerning QoL has been published with regard to neurological and non-neurological entities. This study summarizes data from a study in 717 persons with remitting-relapsing multiple sclerosis (MS). Of them,576 could be reevaluated longitudinally after 1 year of treatment with interferon-beta 1a (44 microg subcutaneous Rebif once weekly). Compared to populations of healthy controls or other patients, considerable reductions in the eight subscales and both physical and emotional sum scales of the German version of the short form of the Rand Health Questionnaire (SF-36) questionnaire were assessed. These reductions were even more pronounced in persons with gait impairments. Most SF-36 scales only modestly correlated to physical disability. This indicates that QoL as reported by patients does not depend solely on the physical symptoms of MS. Most findings remained stable for the study population as a whole during 1 year of therapy, while statistically significant improvements were found in clinical responders as defined in this study (relapse-free, physically stable, stable or improved in physician's judgement). Side effects of therapy were not reflected in lower QoL scale values. Implications of findings for future concepts in MS therapy are discussed.

Reversal of inherent multidrug-resistance in primary human renal cell carcinoma cell cultures by S 9788.

In a panel of 14 primary cultures of human renal cell carcinomas the reversal of inherent multidrug-resistance by S 9788, a new triazinoaminopiperidine derivative, was analysed. In combination with doxorubicin S 9788 revealed an evident reversal of multidrug resistance in 12 cell cultures. Two cell cultures remained unaffected. An association between reversal and P-glycoprotein (P-170) expression suggests that S 9788 exerts its activity through P-glycoprotein.

[Fotemustine, a new nitrosourea derivative. Current status of development]. / Fotemustin, ein neues Nitroso-Harnstoff-Derivat. Aktueller Stand der Entwicklung.

Fotemustine is a new chloronitrosourea recently developed by the French company Servier. It is chemically characterized by the graft of an aminophosphonic acid on the chloronitrosourea radical, which makes it highly lipophil. The preclinical studies revealed a lower mutagenicity and hepatotoxicity when compared to BCNU. The pharmacokinetic studies showed a high body clearance and a short half-life. The phase I study enabled us to determine the definitive treatment schedule: 100 mg/m2/week during 3-4 consecutive weeks followed by 5 weeks' rest and a maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Fotemustine should be given as a 1-h intravenous infusion, protected from daylight. There was no life-threatening toxicity and positive activity was observed in different tumors and especially melanomas. This indication was thus chosen for the phase II study. Among the 153 evaluable patients, the response rate reached 24.2%. It depended on the location of the metastatic sites, with 25% brain metastases, 19.2% visceral metastases, 8.8% liver metastases and 31.8% skin and lymph node metastases. The median duration of response was 22 weeks. The median overall survival of responding patients reached 85 weeks, while it dropped to 52 weeks in case of minor response or stabilization and 17 weeks in case of progression. The hematological toxicity was moderate (WHO grade III and IV: 46.3% leukopenia and 40.3% thrombopenia) and delayed as for other nitrosoureas (nadir: white blood cells: day 44 and thrombocytes: day 35).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevalence of polyneuropathies in patients with chronic obstructive lung disease]. / Untersuchungen zur Polyneuropathieprävalenz bei COLD-Patienten.

A multicentric study of 151 COLD patients confirmed the increased prevalence of peripheral polyneuropathies (PNP) in hypoxaemic patients with chronic obstructive lung disease (COLD). 43 (28%) of these 151 COLD patients showed a clinically manifest PNP, whereas in a comparative group of 32 asthmatics there were only 2 clinical PNP cases. Patients with known risk factors for PNP were not included in the study. The polyneuropathy observed in such patients is usually mild, mainly sensorial, distal and leg-accentuated. Of 52 COLD patients with a PaO2 up to 55 Torr, polyneuropathy was seen in 21 (40%), and of 59 COLD patients with a PaO2 above 60 Torr, 10 (17%) had polyneuropathy. In multifactorial genesis (as would be expected), the degree of severity of hypoxaemia (calculated as reduction of the actual PaO2 value below the age-adjusted nominal value), as well as the age of the patient, are statistically significant predictors of clinically manifest PNP.

Biotransformation and pharmacokinetics of tetrazepam in man.

The pharmacokinetics and the metabolism of tetrazepam (Musaril) were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg in tablet form (commercially available formulation). Tetrazepam and nortetrazepam were measured in serum using a selective and sensitive HPLC method. Urinary metabolites were identified after acid hydrolysis and thin-layer chromatographic separation. Tetrazepam is rapidly absorbed after oral administration with a lag-time of 0.45 +/- 0.10 h and reaches a peak serum level of 0.57 +/- 0.06 mg/l at 1.92 +/- 0.19 h after administration. The drug is largely distributed in the organism with an apparent volume of distribution of 225 +/- 40 l. The substitution of the phenyl moiety in the 5-position by a cyclohexenyl ring results in a different metabolism when compared to other benzodiazepines. This different metabolic pathway is the reason why only very small levels of active metabolites are present in serum. Therefore it seems reasonable, at least from the pharmacokinetic point of view, to attribute pharmacologic activity of tetrazepam mainly to the parent drug. Tetrazepam is eliminated with a half-life of 14.9 +/- 4.4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed.