A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.     

Psychiatric diseases and their treatment in general practice in Germany. Results of a World Health Organization (WHO) study

As part of an international study initiated by the World Health Organization (WHO) about psychological disorders in primary health care, patients in the Federal Republic of Germany were compared with patients in other European centres. Patients from Germany do not differ from other European patients in respect to sociodemographic variables or psychiatric disorders. The most frequent CIDI-based diagnoses recorded in patients attending general practices are current depressive episodes (8.6%), generalized anxiety disorders (8.5%), neurasthenia (7.5%), and alcohol dependence (6.3%). In 20.9% of the patients at least one psychiatric diagnosis based on ICD-10 was recorded. In Germany significantly lower global ratings of health status are given than in other European centres although there is no difference in diagnostic prevalence rates. The recognition rate, i.e. the agreement between the CIDI-based ICD-10 diagnoses and the recognition as a case by the physician, is 56.2%-60.2%. On the other hand, the CIDI detects 90% of the patients described as psychologically ill by the physicians if subthreshold cases are also counted, or 46.4% if only defined diagnoses are taken into account. There is a significant correlation between severity of the psychiatric disorder and disability in social functioning. In Mainz and in the other European countries the disability rate of patients with a well-defined disorder is between 67.0% and 72.7%, whereas in Berlin this relation is not as clear, because especially in East Berlin there is a higher rate of unemployment in view of the political situation. Drug treatment is prescribed for 16.1% of the patients in primary care for psychiatric disorders. Half the patients recognized by physicians as cases receive medication. In the rest of Europe patients receive significantly more tranquillizers than in Germany, where the use of herbal drugs is more wide spread.     

Numerical investigation of the convection of heat-emitting liquid reactor materials taking stratification into account

Conclusions The calculations for the different levels of volume heat release showed that the integral heat fluxes at the lateral and top surfaces are virtually independent of the scenario of convective flow. However, the maximum of the heat flux on the lateral surface in the homogeneous case is 1.5–1.6 times higher than the maximum heat flux in the stratified case. This could result in larger mechanical loads on the reactor vessel and therefore more stringent requirements on the cooling of the outer surface of the reactor vessel. Institute of Fast Reactors, Russian Academy of Sciences. Translated from Atomnaya énergiya, Vol. 76, No. 5, pp. 406–411, May, 1994.     

Juvenile chronic arthritis: a cephalometric analysis of the facial skeleton

A retrospective cross-sectional cephalometric investigation was undertaken to examine the facial form of a group of Finnish children with juvenile chronic arthritis (JCA). Following digitization, the radiographs were divided into three age groups, and according to whether or not 'bird-face' deformity was present. From a total of 67 cases (39 females and 28 males) 19 per cent were judged to be 'affected'. Analyses were carried out and the groups compared using t-tests. The mandible was found to be smaller both in ramal height and body length in the affected sample, with reduction in posterior face height being only partly compensated by increase in bony apposition at the angle producing antegonial notching. There was posterior rotation of the mandible with a reduction in angles S-N-B and S-N-Pog, and an increase in the gonial angle, the angle between the mandibular plane and S-N, maxillary, and occlusal planes. The changes in the maxilla were less marked. Although S-N-A was reduced in all three age groups, it was not significantly so. Maxillary length (ANS-PNS) was significantly smaller in the two younger age groups. In the vertical plane maxillary dimensions were reduced in the two younger age groups. A highly significant increase in the occlusal to maxillary planes angle was observed in all groups. There was, however, no difference in S-N to maxillary planes angle, indicating a more steeply inclined occlusal plane due to subnormally erupted maxillary molars. Although the inter-incisal angle was reduced there was no significant difference in the incisor inclinations in relation to the jaws and despite the posterior rotation of the mandible there was no significant increase in size of overjet or in the frequency of anterior open bite.     

Topical use of aprotinin in open heart operations

Among various pharmacological agents used to reduce bleeding after open-heart operations, high-dose aprotinin therapy seems most promising. However, its long-term effects are still obscure; there is almost always possibility of bypass graft occlusions produced by the hypercoagulable state induced by aprotinin in coronary bypass operations. Topical application of aprotinin into the pericardial cavity could prevent the adverse effects. Fifty patients were prospectively studied to evaluate the effects of topical aprotinin. One million KIU of aprotinin was poured into the pericardial cavity before closure of the sternotomy in group 1 (n = 25). Patients in group 2 (n = 25) served as controls. Total postoperative bleeding was significantly reduced in group 1 when compared with that of group 2 (722.7 +/- 230.8 versus 1,282.6 +/- 225.7 mL; p < 0.01). The use of banked donor blood products was significantly less in group 1 than in group 2 (0.33 +/- 0.67 versus 1.36 +/- 0.86 units; p < 0.01). These results show that topical use of aprotinin reduces post-operative blood loss and need for transfusion. It seems promising and warrants further studies to be done.     

Hepatic and pancreatic effects of polyenoylphosphatidylcholine in rats with alloxan-induced diabetes

In neonatally allylestrenol treated animals in adult age a single benzpyrene treatment significantly decreases the female and significantly increases the male rat's sexual activity. Three month old females display the negative sexual behavioral effect of neonatal allylestrenol treatment less than the six month old ones. The benzpyrene treatment in adult age decreases the sexual activity of male rats. The experiments call the attention to the modifying effect of perinatal steroid treatments to similar exposure in adult age.     

Presynaptic potassium channels

The past year has witnessed some significant improvements in our understanding of the molecular diversity, subunit composition, and functional properties of K+ channels in heterologous expression systems. Immunocytochemical studies have yielded important information on the localization of K+ channel proteins to synaptic terminals in mammalian brain. Although a coherent picture of native presynaptic K+ channels' function in the mammalian central nervous system is not yet available, it may emerge from improvements in patch-clamp techniques and new applications of targeted knock-out technologies.     

Effective index drift from molecular hydrogen diffusion inhydrogen-loaded optical fibres and its effect on Bragg gratingfabrication

When hydrogen loading is used to enhance the photosensitivity of silica-based optical waveguides and fibres, the presence of molecular hydrogen dissolved in the glass matrix changes the effective index of propagation of guided optical modes by as much as 0.05%. Real-time monitoring of the reflectivity spectrum of Bragg gratings written in such conditions shows that the centre wavelength follows the changes in hydrogen concentration due to diffusion and reaction with glass defects