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.     

SARs are cis DNA elements of chromosome dynamics: synthesis of a SAR repressor protein

SARs are candidate DNA elements for defining the bases of chromatin loops and possibly for serving as cis elements of chromosome dynamics. SARs contain numerous A tracts, whose altered DNA structure is recognized by cooperatively interacting proteins such as topoisomerase II. We constructed multi-AT hook (MATH) proteins and demonstrate that they specifically bind the clustered A tracts of SARs in chromatin and chromosomes. They are also potent inhibitors of chromosome assembly in mitotic Xenopus extracts, demonstrating the importance of SARs in this process. Titration of SARs with MATH20 (20 hooks) blocks shape determination of chromatids but not chromatin condensation per se. SARs are also required for shape maintenance of chromosomes. If MATH20 is added after formation of chromatids, they collapse and are reshaped by an active, mitotic process into spherical chromatid balls.     

Noninvasive real-time multipoint temperature control for ultrasoundphased array treatments

A method for noninvasively estimating spatiotemporal temperature changes in samples using diagnostic ultrasound, and using these as inputs to a multipoint ultrasound phased array temperature controller, is presented in this paper. This method is based on a linear relationship between the apparent tissue echo pattern displacements and temperature, as seen along A-lines acquired with diagnostic ultrasound when the sample is heated by external heating fields. The proportionality constant between echo displacement and temperature is determined by the local change in speed of sound due to temperature and the linear coefficient of thermal expansion of the material. Accurate estimation of the displacements and proportionality constant yields accurate calibrated high-resolution (1 mm spatial, sub-°C) noninvasive sample temperature estimates. These are used as inputs to a multipoint temperature controller, capable of controlling ultrasound phased array treatments in real-time. Phantom and in vitro results show that the noninvasively estimated temperature values can effectively be used to control ultrasound hyperthermia treatments, almost replacing invasive thermocouple measurements. The mathematical background and assumptions of the noninvasive temperature estimator and the controller are presented in this paper, together with experimental results showing estimator and controller performance and limitations. To the best of our knowledge, this paper presents the first demonstration of real-time treatment control based entirely on noninvasive temperature estimates     

Wind energy systems

Wind energy has matured to a level of development where it is ready to become a generally accepted utility generation technology. A brief discussion of this development is presented, and the operating and design principles are discussed. Alternative designs for wind turbines and the tradeoffs that must be considered are briefly compared. Development of a wind energy system and the impacts on the utility network including frequency stability, voltage stability, and power quality are discussed. The assessment of wind power station economics and the key economic factors that determine the economic viability of a wind power plant are presented     

Analysis of planar arrays of shunt slots in ridged waveguides

Planar infinite arrays, comprising longitudinal slots cut in ridged waveguides, are analysed using a Galerkin formulation for the tangential electric field at both slot interfaces, combined with the finite element method for generating the waveguide Green function used in the integral equation. Computations agree very well with previously documented results     

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.