Luteinizing hormone-releasing hormone agonist triptorelin in combination with cytotoxic chemotherapy in patients with advanced ovarian carcinoma. A prospective double blind randomized trial. Decapeptyl Ovarian Cancer Study Group.

BACKGROUND: Several lines of evidence suggest that the proliferation of ovarian carcinoma might be stimulated by gonadotrophins. A number of Phase I/Phase II clinical trials have reported that the suppression of endogenous luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone (LHRH) analogs induced objective remissions and/or disease stabilization in 10-30% of patients with advanced refractory ovarian carcinoma. The current study was performed to evaluate whether the addition of LHRH agonist treatment to standard platinum-based chemotherapy could prolong survival of patients with surgically treated Stage III or IV epithelial ovarian carcinoma. METHODS: One hundred and thirty-five patients with Stage III or IV epithelial ovarian carcinoma participated in this prospective randomized double blind trial. After cytoreductive surgery, 69 patients received monthly injections of a depot preparation of the LHRH agonist [D-Trp6] LHRH (triptorelin, 3.75 mg) and 66 patients received placebo until their deaths or termination of trial, respectively. All patients were treated with a standard platinum-based chemotherapy, and, if necessary, with second- or third-line cytotoxic regimens. RESULTS: Endogenous gonadotrophins were reliably suppressed in patients treated with triptorelin. However, their progression free and overall survival were not significantly different from that of patients receiving placebo injections (statistical power > 80% for a difference between both groups of > or = 20%). CONCLUSIONS: The results of this trial suggest that the suppression of endogenous gonadotrophins by conventional doses of an LHRH agonist produces no relevant beneficial effects in patients with advanced ovarian carcinoma who receive standard surgical cytoreduction and cytotoxic chemotherapy.

Epidemiology and out-patient care in Parkinson's disease--results from a pilot-study in northern Germany (Schleswig-Holstein).

An attempt was made to estimate prevalence on Parkinsonism using consultation rates in physicians' practices in a two-step, one-phasic pilot study in a rural-urban area of Northern Germany. Though participation of physicians was low, reported rates for Parkinsonian patients (183/100,000) were in the range yielded in comparable areas, but by different methodology. Only 64% of a large subsample of patients used L-Dopa preparations for therapy. Confirming previous results the objective records of doctors and the subjective notices of patients regarding disease state showed considerable differences in several important items.

[Biochemical aspects of the evaluation of fixed drug combinations]. / Biometrische Aspekte zur Bewertung fixer Arzneimittelkombinationen.

Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prevalence of Parkinson disease in West Germany--are general practice data a suitable survey instrument?]. / Prävalenz des Morbus Parkinson in der Bundesrepublik Deutschland--Sind Praxiserhebungen ein geeignetes Untersuchungsinstrument?

Investigations on prevalence rates in idiopathic Parkinson's disease (IPD) have raised fairly different results due to variations in methodology. Door-to-door studies in circumscribed geographical areas revealed lower prevalence rates in China and Japan compared to countries of the Western hemisphere. Due to the health system organization and present legislation on personal data referral such systematic door-to-door epidemiological surveys seem nearly impossible in the Federal Republic of Germany. The present pilot study therefore used doctor's practices as a means to obtain evidence rates on patients diagnosed on and treated for IPD. Standardized questionnaires with appropriate items regarding symptoms, diagnosis and treatment for the disease were distributed by mail or personally in 387 practices of general practitioners, internal specialists, neurologists, and psychiatrists and 3 hospital ambulances in the handestadt Lübeck, the Kreis Stormarn and the Kreis Herzogtum Lauenburg. Investigation time was March, 1 to June, 30, 1987. Each patient cared for IPD was to fill up a personal questionnaire with similar items as well. A second estimation of prevalence was made according to published sales of L-Dopa drugs for treatment of IPD. The third estimation used statistics about disease pattern of the Bundesverband der Allgemeinen Ortskrankenkassen (AOK). Participation of doctors was to be maintained high by varying methods of repeated requirements during the investigation period. 41 of 210 (20%) of the doctors requested by mail and 126 of the 180 visited physicians (70%) participated in the study with 1018 patients altogether. The estimate of prevalence for the Hansestadt Lübeck was 188, for the Kreis Stormarn 206 and for the Kreis Herzogtum Lauenburg 147 patients per 100,000 (183 in toto). According to latest data on L-Dopa drug sale the prevalence rate in the above areas was 144/100,000. According to the statistics of disease pattern of the AOK the prevalence estimate was 185/100,00 assured persons. These results are discussed with special emphasis on the methodological aspects.

[Effect of demographic changes on the case rate and days of care for hospitalized internal medicine patients]. / Einfluss demographischer Anderungen auf Fallzahlen und Pflegetage hospitalisierter internistischer Patienten.

Using case categories at the Center for Internal Medicine of the Medical University at Lübeck and predictions of future population trends by the German Federal Statistical Office, likely future numbers of inpatients and days of hospital stay were calculated. Assuming other conditions remaining constant, an annual rise of 0.9% of medical cases is to be expected until the year 2005. An increase above this average is expected for cases of cardiovascular and respiratory disease and of malignant neoplasms, while it will be below average for renal or gastrointestinal diseases. These data are similar to comparable projections made, on the basis of Federal statistics, of hospital cases registered with local health insurance schemes. In addition they indicate an increase of 3% for all non-paediatric admissions up to 2005.

The effect of dietary fiber on postprandial serum digoxin concentration in man.

The postprandial digoxin concentrations in serum were measured for 4 hr by radioimmunological assay in six healthy volunteers who had received 0.8 mg beta-acetyldigoxin by the oral route. Digoxin was given together with a formula diet containing as admixture, respectively, wheat bran, microcrystalline cellulose, pectin, carrageenan, and carob seed flour. The various additions did not reduce the mean digoxin concentrations in serum. After carob seed flour, the concentrations were significantly (P less than 5%) higher, as compared to the control. After microcrystalline cellulose, pectin, and wheat bran the mean peak concentrations were reached later than in the control state.

[Comparison between ambulatory or stationary treatment systems for patients with rhematoid arthritis with reference to the development of the family situation]. / Vergleich des ambulanten und des Kurbeha ndlungs-systems für chronische Polyarthritiker im H inblick auf die Entwicklung der familiären Situation.

UNLABELLED: The evaluation of a detailed questionaire which was issued to 44 German female rheumatoid arthritis patients (family mothers) who underwent "Kur" treatment courses and a comparable group of Dutch patients who had ambulatory treatment only shows little advantage to the "Kur" system). The "Kur" patients had adjusted somewhat better to their illness and had retained more easily the extra-familial social contacts. In contrast, statistically significant advantages were clearly evident in the Dutch ambulatory treatment programm: 1. Over-all reduction in "feeling ill" 2. Reduced stress in association with the objectively reduced joint mobility 3. Reduced stress in association with pain 4. The support of the patient by immediate family members and other relatives is generally better 5. Better patient support possibilities by family friends 6. Reduced negative effects on family life 7. Reduced disruptive effects in relationships between the patients and their husbands and children 8. Higher degree of satisfaction with physicians and the treatment. IN CONCLUSION: Even if national behavioral differences are taken into consideration, the ambulatory system as practiced in Holland seems to hold significant advantages to the "Kur" system.

The effect of dietary fiber on the postprandial serum vitamin A concentration in man.

In 11 normal female subjects, ages 19 to 22 years, the postprandial serum vitamin A concentration was measured 3, 5, 7, and 9 hr after oral administration 300,000 IU vitamin A-palmitate given with a formula diet to which was added 40 g wheat bran, 40 g microcrystalline cellulose, 15 g apple pectin, 15 g guar flour, 15 g carob bean flour, or 20 g carrageenan. When vitamin A was given together with guar flour and apple pectin 3 hr after starting the experiment, the mean serum vitamin A concentration was significantly higher than in controls. Areas under serum vitamin A concentration curves, taken as a measure of the amount of vitamin A absorbed, were significantly higher when the vitamin was administered together with the investigated dietary fiber substances.

[Lidocaine prophylaxis in the pre-hospital phase of acute myocardial infarction (author's transl)]. / Lidocain-Prophylaxe in der Prähospitalphase des akuten Myokardinfarkts.

In a double blind study performed in cooperation with 69 emergency doctors and general practitioners in the catchment areas of the university and of the city hospital in Lübeck the action of intramuscular lidocaine on mortality and on the incidence of arrhythmias was investigated in patients with acute myocardial infarction aged less than 70 years. The mortality in the lidocaine group was significantly lower than in the placebo group. The incidence of ventricular arrhythmias up to 120 minutes after the lidocaine injection was also lower than in the placebo group. However, the only case of primary ventricular fibrillation was in the lidocaine group. As the difference in mortality between the two groups appeared at a time when an antifibrillatory action of lidocaine can no longer be assumed one must question whether the positively beneficial effect was real or whether the lower mortality was in fact due to primarily milder disease in the lidocaine group.