Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Environmental tobacco smoke and lung cancer: a case-control study in Germany

To assess the association between exposure to environmental tobacco smoke (ETS) and lung cancer, the authors personally interviewed 292 lifelong nonsmoking lung cancer cases (recruited from 15 hospitals in the study area) and 1,338 nonsmoking controls (randomly selected by population registries) between 1990 and 1996 in Germany. Subjects were asked by a standardized questionnaire about exposure to ETS in childhood, by spouse, at work, and in transportation and social settings. Several indicators of these different sources of exposure were investigated, using not or low exposed subjects as the reference category. The most informative quantification index was weighted duration of exposure (hours x level of smokiness). No effect of ETS exposure during childhood and no clear effect of spousal ETS were observed. However, for the highest category of exposure, clear effects of ETS at the workplace (odds ratio (OR) = 1.93; 95% confidence interval (CI): 1.04, 3.58), in vehicles (OR = 2.64; 95% CI: 1.30, 5.36), and from all sources combined (OR = 1.39; 95% CI: 0.96, 2.01) were found. Adjustment for occupational carcinogens, radon, and diet did not appreciably change the results. These findings suggest that exposures to high levels of ETS at the workplace and in other public indoor settings appear to be important risk factors for lung cancer risk in nonsmokers.     

Targeted Gene Transfer for Adenocarcinoma Using a Combination of Tumor-specific Antibody and Tissue-specific Promoter

We have developed a highly specific gene transfer method for adenocarcinoma using a monoclonal antibody against tumor-specific antigen coupled with a plasmid containing the carcinoembryonic antigen (CEA)-specific promoter. The chimeric CEA promoter (CC promoter), which contained an enhancer from the immediate early gene of cytomegalovirus and the CEA promoter, achieved 4- to 5-fold higher transgene expression in CEA-producing cells than the original CEA promoter while maintaining CEA specificity. Furthermore, a complex of a monoclonal antibody against Lewis Y antigen (LYA), the CC promoter-containing plasmid and cationic liposomes (DOTAP) achieved specific gene expression in CEA-producing and LYA-positive adenocarcinoma cell lines that was 200-fold more efficient than in CEA-non-producing and LYA-negative cell lines during a short in vitro incubation. This strategy may be applicable for clinical gene therapy.     

Patterns and predictors of inpatient falls and fall-related injuries in a large academic hospital.

OBJECTIVES: Most research on hospital falls has focused on predictors of falling, whereas less is known about predictors of serious fall-related injury. Our objectives were to characterize inpatients who fall and to determine predictors of serious fall-related injury. METHODS: We performed a retrospective observational study of 1,082 patients who fell (1,235 falls) during January 2001 to June 2002 at an urban academic hospital. Multivariate analysis of potential risk factors for serious fall-related injury (vs no or minor injury) included in the hospital's adverse event reporting database was conducted with logistic regression to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CI95) RESULTS: The median age of patients who fell was 62 years (interquartile range, 49-77 years), 50% were women, and 20% were confused. The hospital fall rate was 3.1 falls per 1,000 patient-days, which varied by service from 0.86 (women and infants) to 6.36 (oncology). Some (6.1%) of the falls resulted in serious injury, ranging by service from 3.1% (women and infants) to 10.9% (psychiatry). The most common serious fall-related injuries were bleeding or laceration (53.6%), fracture or dislocation (15.9%), and hematoma or contusion (13%). Patients 75 years or older (aOR, 3.2; CI95, 1.3-8.1) and those on the geriatric psychiatry floor (aOR, 2.8; CI95, 1.3-6.0) were more likely to sustain serious fall-related injuries. CONCLUSIONS: There is considerable variation in fall rates and fall-related injury percentages by service. More detailed studies should be conducted by floor or service to identify predictors of serious fall-related injury so that targeted interventions can be developed to reduce them.     

Number of Sexual Partners and Associations with Initiation and Intensity of Substance Use

We dissected associations between initiation and intensity of substance use and number of sexual partners using pooled data from high school seniors (weighted n = 13,580) who participated in the 1999–2007 Youth Risk Behavior Surveillance System (YRBS), a cross-sectional, nationally representative survey. In multinomial multivariable logistic regressions, number of sexual partners steadily increased as substance use intensified from never use to experimental/new user to heavy use across all substances for both male and females. Severity of substance use is more closely related to, and thus a better indicator of, higher number of sexual partners than age of substance use onset.