Ein “Erythema pustulatum grave (exanthematicum)”

Ohne ZusammenfassungMit einem graphischen Schema des Krankheitsverlaufes.     

Development of acute exposure guideline levels for airborne exposures to hazardous substances

Hazardous substances can be released into the atmosphere due to industrial and transportation accidents, fires, tornadoes, earthquakes, and terrorists, thereby exposing workers and the nearby public to potential adverse health effects. Various enforceable guidelines have been set by regulatory agencies for worker and ambient air quality. However, these exposure levels generally are not applicable to rare lifetime acute exposures, which possibly could occur at high concentrations. Acute exposure guideline levels (AEGLs) provide estimates of concentrations for airborne exposures for an array of short durations that possibly could cause mild (AEGL-1), severe, irreversible, potentially disabling adverse health effects (AEGL-2), or life threatening effects (AEGL-3). These levels can be useful for emergency responders and planners in reducing or eliminating potential risks to the public. Procedures and methodologies for deriving AEGLs are reviewed in this paper that have been developed in the United States, with direct input from international representatives of OECD member-countries, by the National Advisory Committee for Acute Exposure Guidelines for Hazardous Substances and reviewed by the National Research Council. Techniques are discussed for the extrapolation of effects across different exposure durations. AEGLs provide a viable approach for assisting in the prevention, planning, and response to acute airborne exposures to toxic agents.     

Understanding hard-core drug use among urban Puerto Rican women in high-risk neighborhoods

The objectives of the current study were to determine the incidence and prevalence of hard-core drug (HCD) use and to explore the predictors of HCD use in a three-wave longitudinal study of women ages 18-35 living in urban areas of high drug traffic in Puerto Rico. Prevalence of HCD use was determined by positive self-report or positive toxicological tests for crack, cocaine, or heroine at baseline and follow-up periods. Incidence density was calculated using Poisson methods. Predictors of HCD use were identified using the generalized estimating equation (GEE) approach. Prevalence rates fluctuated between 16.3 at baseline and 12.6 and 14.6 at subsequent waves. Incidence of crack/cocaine or heroine ranged from 7.4 to 6.3 per 100 person years. Low education, unemployment, current alcohol use, and severe partner violence predict incident HCD use. Therefore, prevention programs for HCD use must consider strategies to promote social mobility and empowerment and to mitigate violence against women.     

Time from treatment to subsequent diagnosis of brain metastases in stage III non-small-cell lung cancer: a retrospective review by the Southwest Oncology Group.

PURPOSE A retrospective review of the Southwest Oncology Group (SWOG) database was undertaken to review the incidence and timing of diagnosis of brain metastases in patients undergoing combined-modality therapy for stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Four hundred twenty-two eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG protocols. Treatment varied with protocol but consisted of concurrent cisplatin-etoposide and radiation in all patients, with a surgery arm in two of the four protocols. Results Of the 422 total patients, 268 (64%) have experienced disease progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of the 268 patients with disease progression, progression in the brain only, in the brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of patients, respectively. Time from treatment to diagnosis of disease progression in the brain in 71 patients was as follows: during treatment, 16 relapses (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous histology and young patient age were the only significant predictors for increased risk of early relapse with brain metastases. CONCLUSION Brain metastases often develop early in the course of treatment for stage IIIA/B NSCLC. The statistical designs of ongoing trials of prophylactic cranial irradiation in stage III NSCLC have taken this into account.     

Inequalities in use of specialty mental health services among Latinos,African Americans,and non-Latino whites

OBJECTIVE: The authors investigated whether there are disparities in the rates of specialty mental health care for Latinos and African Americans compared with non-Latino whites in the United States. METHODS: Data were analyzed from the 1990-1992 National Comorbidity Survey, which surveyed a probability sample of 8,098 English-speaking respondents aged 15 to 54 years. Respondents self-identified their race or ethnicity, yielding a sample of 695 Latinos, 987 African Americans, and 6,026 non-Latino whites. Data on demographic characteristics, insurance status, psychiatric morbidity, whether the respondent lived in an urban or a rural area, geographic location, income, and use of mental health services were determined for each ethnic or racial group. Logistic regression analyses were used to examine the associations between ethnic or racial group and use of specialty services, with relevant covariates adjusted for. RESULTS: Significant differences between ethnic groups were found in demographic characteristics, geographic location, zone of residence, insurance status, income, wealth, and use of mental health services. The results indicated that poor Latinos (family income of less than $15,000) have lower access to specialty care than poor non-Latino whites. African Americans who were not classified as poor were less likely to receive specialty care than their white counterparts, even after adjustment for demographic characteristics, insurance status, and psychiatric morbidity. CONCLUSIONS: To understand ethnic or racial disparities in specialty care, the effects of ethnicity or race should be analyzed in combination with variables related to poverty status and environmental context. Further research needs to address the complex construct of social position in order to bridge the gap in unmet need in specialty care.     

Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma

PURPOSE: The treatment of malignant pleural mesothelioma remains a therapeutic challenge, with median survival rates of about 12 months and local failure rates of up to 80%. Our institution recently published results showing that extrapleural pneumonectomy (EPP) followed by hemithoracic radiation yielded excellent local control. This paper reports our technique for high-dose hemithoracic radiation after EPP. METHODS: Between 1990 and 2001, 35 patients with malignant pleural mesothelioma were treated with EPP followed by hemithoracic radiation therapy (median dose: 54 Gy, range: 45-54 Gy) at Memorial Sloan-Kettering Cancer Center. EPP was defined as en bloc resection of the entire pleura, lung, and diaphragm with or without resection of the pericardium. The radiation therapy target volume was the entire hemithorax, including the pleural folds and the thoracotomy and chest tube incision sites. Patients were treated with a total dose of 5400 cGy delivered in 30 fractions of 180 cGy. Radiation therapy was well tolerated, and toxicity data are described. RESULTS: Of the 35 patients analyzed, 29 patients were male, and 18 had right-sided tumors. Twenty-six had epithelioid histologies. UICC stage was I in 4, II in 11, III in 19, and IV in 1 patient. As shown by axial and sagittal isodose distributions, we were able to deliver adequate doses to the target volume while limiting dose to critical structures such as heart, spinal cord, liver, and stomach. The most common toxicities were RTOG Grades 1 and 2 nausea and vomiting, as well as lung, esophageal, and skin toxicities. CONCLUSION: Extrapleural pneumonectomy followed by high-dose hemithoracic radiation therapy is a feasible treatment regimen that is well tolerated for patients with malignant mesothelioma. We have demonstrated adequate dose distributions, using a combined photon and electron technique with blocking of critical normal structures.     

Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model

OBJECTIVE: Innovative treatments are needed for metastatic disease involving the pleura. NV1020 is a novel, multimutated, replication-restricted herpes simplex virus under investigation for its ability to selectively kill tumors by means of direct cell lysis. This study examines NV1020 in a rat model of pleura-based lung cancer. METHODS: Cytotoxicity and viral proliferation were evaluated in vitro by exposure of the human non-small cell lung cancer cell line A549 to virus. NV1020 was also tested in an in vivo pleura-based cancer model established by injecting 1 x 10(7) A549 cells into the thoracic cavity of nude rats. Intrapleural treatments (1 x 10(7) viral particles) were given 3 hours or 3 days after tumor injection to model treatment of microscopic or macroscopic disease (n = 8-9/group). Tumor burden was assessed at 5 weeks. NV1020 infection and dissemination within the thoracic cavity was determined by means of immunohistochemistry. RESULTS: In vitro, at multiplicities of infection (viral particles per tumor cell) of 0.01, 0.1, and 1.0, cell killing of A549 by NV1020 was 66%, 90%, and 97%, respectively, at 7 days after infection. Viral burst occurred by day 2. Intrapleural treatment was effective for both the microscopic (P <.001) and macroscopic (P <.05) in vivo tumor models. Virus was detectable by means of immunohistochemistry in tumors but not in adjacent normal intrathoracic tissues. CONCLUSIONS: NV1020 is not only highly cytotoxic to the human lung cancer line A549 in vitro but can be delivered in a clinically relevant fashion to safely and effectively treat pleura-based tumor in vivo in a rat model.     

An initial experience with FDG-PET in the imaging of residual disease after induction therapy for lung cancer

BACKGROUND: The 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) imaging is an advance over computed tomography alone in the staging of untreated nonsmall cell lung cancer (NSCLC). Aside from one 9-patient study, there are no data comparing FDG-PET imaging with surgical staging of NSCLC after induction therapy. METHODS: We reviewed our institutional experience with FDG-PET imaging followed by surgical staging of nonsmall cell lung cancer after induction therapy. A nuclear physician blinded to surgical findings reviewed the FDG-PET scans and assigned a clinical TNM stage. A thoracic surgeon assigned a pathologic TNM stage. Then the clinical TNM stage and the pathologic TNM stage were compared. RESULTS: Fifty-six patients (30 males and 26 females; median, age 60) with nonsmall cell lung cancer underwent chemotherapy (40 patients), chemoradiation (11 patients), or radiation alone (5 patients) followed by PET and operations. PET had a positive predictive value of 98% for detecting residual viable disease in the primary tumor. PET over-staged nodal status in 33% of patients, under staged nodal status in 15%, and was correct in 52%. PET correctly classified all patients with M1 disease. CONCLUSIONS: Positron emission tomography after induction therapy accurately detects residual viable primary tumor, but not the involvement of mediastinal lymph nodes.     

Phase II study of a radiotherapy/etoposide combination for patients with newly malignant gliomas

Purpose: Etoposide, a semisynthetic derivative of podophyllotoxine, is a topoisomerase II inhibitor. This drug is currently used in several types of human cancer. The aim of this study was to evaluate the efficacity and tolerance of a near-concurrent association of radiotherapy and etoposide for newly malignant gliomas. Methods: From May 1995 to December 1996, 30 malignant glioma patients were included in this phase II study; 16 patients underwent surgical tumor resection, and a stereotactic biopsy was performed in 14 patients. Standard cranial irradiation and six courses of etoposide (100 mg/m², ×days 1–3) were administered. The first course of etoposide was administered on days 1–3 of radiotherapy and was resumed in the week following the end of radiotherapy. Treatment was consolidated by further courses of etoposide every 4 weeks. Results: Only 26 patients could be evaluated for the purpose of our study. The median age was 60.1 years, and the median Karnofsky performance score (KPS) was 80.2. The rate of objective response for evaluable patients was 34.6%, and four complete responses (CR) and five partial responses (PR) were noted. The median survival (MST) was 12 months, and the average overall survival was 12.5 months. Hematological toxicity was mild, and grade 3 or 4 neutropenia (white blood cell count <1500/ml) was noted in three patients, without any sepsis or bleeding. Conclusions: The results obtained in this study are comparable to the best reported results on the combination of radiotherapy and nitrosoureas. The near-concurrent combination of radiotherapy and etoposide seems to be effective and well tolerated in the treatment of newly malignant gliomas. Received: 7 December 1998 / Accepted: 5 February 1999