Response of dermal fibroblast cultures from patients with unusually severe responses to radiotherapy and from ataxia telangiectasia heterozygotes to fractionated radiation

We examined the cytotoxic effects of radiation delivered in daily fractions at clinically relevant doses in plateau phase cultures of skin fibroblast cell strains derived from ataxia telangiectasia (AT) heterozygotes, patients with unusually sensitive responses to radiotherapy, apparently normal patients, and cell bank controls. A gradual linear reduction in surviving fraction versus total dose was observed in the control group, comprised of apparently normal individuals and one patient with a normal clinical response to radiotherapy, after exposure to daily fractions of 2.0 Gy. There was a much steeper decline in surviving fraction among the AT heterozygotes and the group with sensitive responses to radiotherapy, such that after six daily fractions of 2.0 Gy (12 Gy total dose), the mean surviving fraction of the control group was significantly different from that of the AT heterozygotes (P = 0.0009) and that of the patients with unusually sensitive responses to radiotherapy (P = 0.0002). We propose that this assay may be a useful means of identifying cell strains from AT heterozygotes. Based on these results, the hypothesis is discussed that patients who suffer unusually sensitive clinical reactions to radiotherapy may be AT heterozygotes.     

Mediastinal space-occupying lesion with reduced perfusion of the left lung. Thoracic aortic aneurysm with compression of the left pulmonary artery

CONTEXT: An increase in the recreational use of personal watercraft (PWC) raises concern about an increase in associated injuries on a national level. OBJECTIVE: To estimate the relative frequency, types of injury, and demographic features of persons injured while using PWC in the United States. DESIGN: Case series. SETTING: Emergency department (ED) visits to hospitals participating a national probability sample. PARTICIPANTS: All persons treated for PWC-related injury from January 1,1990, through December 31, 1995. RESULTS: An estimated 32954 persons (95% confidence interval [CI], 22919-42989) with PWC-related injuries were treated in US hospital EDs, of which 3.5% were hospitalized. Personal watercraft-related injuries have increased significantly from an estimated 2860 in 1990 to more than 12000 in 1995. During this period, the number of PWC in operation increased 3-fold from approximately 241500 in 1990 to an estimated 760000 in 1995. The most prevalent diagnoses were lacerations, contusions, and fractures. MAIN OUTCOME MEASURES: The estimated number and percentage of patients treated in EDs for PWC-related injuries, by year, age, sex, and the number and rate per 1000 of PWC in operation by year. CONCLUSIONS: Since 1990, there has been at least a 4-fold increase in injuries associated with an increase in the recreational use of PWC. The rate of ED-treated injuries related to PWC was about 8.5 times higher (95% CI, 8.2-8.8; 1992 data) than the rate of those from motorboats. Specific training and adult supervision is recommended for minors using PWC. Furthermore, medical practitioners should encourage personal flotation device use and other protection for their patients who are known water enthusiasts.     

Patterns of DSM-III-R alcohol dependence symptom progression in a general population survey

Age of onset reports obtained retrospectively for each symptom of DSM-III-R alcohol dependence (AD) are used to study patterns of lifetime symptom progression in a large general-population survey of people in the United States. It is shown that symptom progression among a substantial majority of respondents can be summarized as movement across three clusters. Cluster A is defined by symptoms of role impairment/hazardous use (A4), use despite social, psychological or physical problems (A6), and drinking larger amounts or over a longer period of time than intended (A1). Cluster B is defined by tolerance (A7) and impaired control (A2, A3). Cluster C is defined by withdrawal (A8, A9) and giving up activities in order to drink (A5). Clusters are shown to follow a time sequence, with at least one symptom in Cluster A usually occurring first, followed by symptoms in Clusters B and C. In all, 83.4% of the symptom cluster transitions estimated from retrospective age of onset reports are consistent with this progression. Progression to AD is differentially predicted by symptom profiles reported at the age of first symptom onset, with persons reporting Cluster C symptoms most likely to progress subsequently to AD. Furthermore, profiles of AD defined by the highest symptom cluster present at AD onset are differentially predicted by prior personal and parental histories of psychopathology and, among men, are predictive of diagnosis persistence.     

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.