Group Similarities in Beliefs Concerning the Causes of Alcohol Problems and the Effectiveness of Means of Overcoming Problem Alcohol Use

Four hundred and eight respondents, who did or did not know persons close to themselves with alcohol problems, from four different racial/ethnic groups (with one group, Filipinos, categorized in terms of whether they were born in the Philippines or in the US.) rated the importance of 19 different causes of problem alcohol use and 22 different means of overcoming problem alcohol use. Rank-order correlations across sexes, persons differing in exposure to problem drinkers, and ethnic groups were nearly all in the 0.90's regarding causation. Correlations of Caucasians' ratings with those of other groups were high, but only in the 0.60's and 0.70'9, chiefly because Caucasians were more prone to regard problem alcohol use as hereditary and as a disease, and less likely to believe problem use to result from social factors. All across-group correlations concerning beliefs about the effectiveness of means of overcoming problems were in the 0.90's. Some of the means of treatment regarded most highly by all groups have not been demonstrated to be effective.     

Direct mapping of MHC class II epitopes

Despite technical improvements, the mapping of MHC class II epitopes within complex antigens by genetic or biochemical methods is still laborious and expensive. Here, we describe a simple and fast procedure to directly map T helper cell epitopes within known antigens by bacterial expression cloning. Short antigenic fragments, created by digestion of the coding sequence of the antigen with frequently cutting restriction enzymes, are randomly ligated to the coding sequence of GFP in a bacterial expression vector. Bacteria expressing antigen-GFP fusion proteins are then fed directly to MHC II+ antigen-presenting cells and probed with antigen-specific T cells. Bacterial colonies recognized by T cells are expanded, and the antigenic fragments identified by plasmid extraction and sequence analysis. This direct epitope identification (DEPI) approach offers several advantages. First, bacterial colonies expressing the antigen in frame with GFP are easily detectable by virtue of their green appearance and thereby reduce the screening effort significantly. Second, short antigenic peptides normally unstable in bacteria are highly expressed when fused to GFP. Third, the uniformly high level of expression of short antigenic peptides fused to GFP permits the identification of epitopes even within proteins which are difficult to express in bacteria. Furthermore, by fusing double-stranded oligonucleotides to the GFP gene, crucial amino acids within T cell epitopes may be defined. Thus, this method not only facilitates the identification of T cell epitopes, but also makes it possible to assess the role of individual amino acids for MHC binding or T cell recognition.     

Familial Transmission of Alcohol Use Norms and Expectancies and Reported Alcohol Use

Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a "normal" quantity-frequency of alcohol use, "problem" quantity-frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity-frequency of alcohol use was moderately negatively correlated with flushing after one drink or less ("fast flushing"), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity-frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent-offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use.     

A six-year epidemiologic review of pneumonia in Department of Veterans Affairs facilities

OBJECTIVE: Pneumonia and acute lower respiratory infections are a major problem in the United States and worldwide. As one of the largest health care organizations in the United States, the Department of Veterans Affairs is an ideal location for an epidemiologic review of pneumonia over an extended period of time. METHODS: Data for this study were retrieved from the Department of Veterans Affairs Austin Automation Center, the central repository for patient data in the Veterans Health Administration (VHA). In addition, specific data regarding penicillin-resistant Streptococcus pneumoniae in VHA facilities were obtained from an annual electronic nationwide census. RESULTS: The case rate of pneumonias as a discharge diagnosis increased during the 6-year period. For the diagnosis group of bronchopneumonia and pneumonia with organism unspecified, the largest subset examined, total numbers and rates for this specific diagnosis increased during the study period. When fiscal year (FY)91 and FY96 were compared, rates increased for three diagnoses: overall pneumonia, pneumonia in infectious diseases classified elsewhere, and pneumococcal pneumonia. Decreases in rates occurred between FY91 and FY96 for pneumonia caused by other specified organisms and other bacterial pneumonia. The total number of discharges from VHA facilities decreased during the 6-year period. CONCLUSIONS: The numbers of episodes of bronchopneumonia and pneumonia with organism unspecified, the largest pneumonia subset, increased during the 6-year period to greater than 27,000 cases. As the number of total discharges from the VHA decreased, the combination of increasing actual numbers and decreasing discharges yielded increased rates for overall pneumonia and certain subsets. These data should be useful in developing aggressive preventive strategies.     

Transitional cell carcinoma of the renal pelvis and ureter: Outcome and patterns of relapse in patients treated with postoperative radiation

We assessed the records of 101 patients with locally advanced transitional cell carcinoma (TCC) of the renal pelvis and ureter treated with postoperative radiation therapy to determine outcome and patterns of failure. Locally advanced disease (i.e., T3–4N0 or N+ disease) was identified in 65 patients. Postoperative radiation was used to treat 86 patients, with a median dose of 35 Gy in 20 fractions over 4 weeks to the tumor bed and regional lymph nodes. There were 15 patients with no residual disease who were offered no further therapy. No patient received postoperative chemotherapy. Prognostic factors were examined using univariate and multivariate analysis, and the patterns of failure were identified after postoperative irradiation. Median follow-up was 9.3 years, during which 76 deaths occurred. The 5-year overall survival was 43% and 10-year survival was 23%. A multivariate analysis identified T3 category, lymph node involvement, and age at diagnosis as significant prognostic factors for survival. Tumor grade was a significant prognostic factor on univariate analysis but not on multivariate analysis. Failure analysis showed that only 36% of patients with locally advanced disease remained relapse free. For this group of patients, distant metastases developed in 53%, and locoregional failured occurred in 35% despite postoperative irradiation. Locoregional failure occurred in 95% of patients with nodal involvement who received postoperative radiation, and 77% of those developed distant relapse. This leads us to conclude that patients with resected locally advanced (T3, T4N0, N+) TCC of the upper urinary tracts have a high risk of relapse and death from disease despite postoperative radiotherapy. Because the main feature of the disease is early distant failure, post-operative chemotherapy is required to improve the outcome for this group of patients.     

Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas.

PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors, including cervical carcinomas. Direct pO(2) measurement requires specialized equipment and expertise that is not generally available. Immunohistochemical measurement of intrinsic tissue markers of hypoxia is an alternative approach. Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy. Tissue sections were labeled using an immunofluorescence technique and CA IX expression in the viable tumor area measured using a semiautomated fluorescence image analysis technique. Results were compared with direct pO(2) values obtained using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA IX expression was examined in a subgroup of patient who underwent multiple biopsies. RESULTS: The median percentage of tumor area staining for CA IX was 3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf pO(2) measurements. Whereas the latter values were predictive of patient outcome, the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated that intratumoral heterogeneity accounted for 41% of the total variance in the data set. CONCLUSIONS: In contrast to some recent studies, we did not find significant associations between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. Probable explanations relate to the problems of sampling error using single biopsies and the existence of biological factors other than hypoxia that influence CA IX levels.     

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma

Purpose: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas.

Methods and Materials: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain ≤6 cm in size, not crossing midline or involving corpus callosum, age 18–70, Karnofsky Performance Status (KPS) ≥70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age ≤50 or >50, and KPS ≥90 or ≤80.

Results: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age ≤50, KPS ≥90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS ≥90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49.

Conclusions: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.