Why elderly veterans choose VA services.
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Aged↗
Biomedical subjects
J D Hamilton
Publications and source records attributed to J D Hamilton.
Outcome of psychiatric hospitalization for very low-functioning demented patients.
The authors determined the outcome of geropsychiatric hospitalization for 73 very low-functioning demented patients (GAF score < 21). General psychiatric symptoms, depression, and agitation decreased significantly, and mean GAF scores increased significantly, with no significant change in cognitive function. Psychiatric hospitalization can meaningfully improve function and quality of life even in this very impaired population. Despite these improvements many patients are discharged to more restrictive settings.
Activities of Daily Living↗
Hepatitis C.
OBJECTIVES: To review the virology, epidemiology, pathogenesis, natural history, clinical manifestations, and current treatment of hepatitis C virus (HCV) infection. DATA SOURCES: The MEDLINE database (1966 to 1996) was searched for English-language articles and abstracts on HCV and non-A, non-B hepatitis. Papers cited in relevant primary articles were also reviewed. STUDY SELECTION: More than 500 original and review articles were evaluated, and the most relevant were selected. DATA EXTRACTION: Data were extracted and reviewed by all authors. DATA SYNTHESIS: In most patients, HCV infection results in chronic hepatitis. The disease is insidious and subclinical but may progress over decades into end-stage liver disease and hepatocellular carcinoma, which makes HCV cirrhosis a leading indication for orthotopic liver transplantation. Current diagnostic methods are highly sensitive and specific, and quantitative assessment of viral load may help to predict and monitor response to treatment. The only available therapeutic option is interferon, and this agent is effective in only a small subset of patients. CONCLUSIONS: Infection with HCV is a significant public health problem that has important clinical and financial consequences. The tailoring of specific therapy according to viral load or genotype, better patient selection, and use of combination drug regimens may improve the chance of viral clearance and sustained biochemical and histologic response. Further understanding of the basic virology of HCV and the exact mechanisms of viral persistence and tissue injury is needed to help define future therapeutic and preventive strategies.
Carcinoma, Hepatocellular↗
Quality in Australian Health Care Study.
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Australia↗
Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.
BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS: We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS: Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS: Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.
Acquired Immunodeficiency Syndrome↗
Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment.
Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).
Acquired Immunodeficiency Syndrome↗
Aquatic risk assessment of a polycarboxylate dispersant polymer used in laundry detergents.
Polycarboxylates enhance detergent soil removal properties and prevent encrustation of calcium salts on fabrics during washing. Laundry wastewater typically reaches wastewater treatment plants, which then discharge into aquatic environments. The yearly average concentration of a 4500 molecular weight (MW) sodium acrylate homopolymer reaching U.S. wastewater treatment plants will be approximately 0.7 mg/L. Publications showing the low to moderate acute aquatic toxicity of polycarboxylates are readily available. However, there are no published evaluations that estimate wastewater removal and characterize the probability of exceedance of acceptable chronic aquatic exposure. WW-TREAT can be used to estimate removal during wastewater treatment and PG-GRIDS can be applied to characterize risk for exceedance in wastewater treatment plant outfalls. After adjustments for the MW distribution of the homopolymer, WW-TREAT predicted that 6.5% will be removed in primary treatment plants and 60% will be removed in combined primary and activated sludge treatment plants. These estimates are consistent with wastewater fate tests, but underestimate homopolymer removal when homopolymer precipitation is included. Acceptable levels of chronic outfall (receiving water) exposure were based on aquatic toxicity testing in algae, fish, and Daphnia magna. PG-GRIDS predicted that no unreasonable risk for exceedance of acceptable chronic exposure will occur in the outfalls of U.S. wastewater plants. Future development of wastewater treatment models should consider polymer MW distribution and precipitation as factors that may alter removal of materials from wastewater.
Acrylates↗
Cytomegalovirus infection following liver transplantation: review of the literature.
Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation.
Animals↗
The Quality in Australian Health Care Study.
A review of the medical records of over 14,000 admissions to 28 hospitals in New South Wales and South Australia revealed that 16.6% of these admissions were associated with an "adverse event", which resulted in disability or a longer hospital stay for the patient and was caused by health care management; 51% of the adverse events were considered preventable. In 77.1% the disability had resolved within 12 months, but in 13.7% the disability was permanent and in 4.9% the patient died.
Adolescent↗
Influence of lead on mineralization during bone growth.
Lead will inhibit skeletal development and localize in areas of bone formation and resorption, but the mechanisms of lead toxicity in bone are largely unknown. This study used an ectopic bone (plaque) induction method to investigate the effect of lead on mineralization of cartilage in growing bone. Demineralized bone matrix was subcutaneously implanted in male Long-Evans rats to induce plaque formation. Of 64 rats which were provided deionized water, 32 were implanted with control matrix (control group). The remaining 32 rats were implanted with matrix containing a target concentration of 200 micrograms lead/g of plaque tissue as ectopic bone (lead-added group). Another group of 32 rats was continuously exposed to 1000 ppm lead in drinking water and subcutaneously implanted with control matrix (drinking water-lead group). Plaques were taken for analysis on Days 8 and 12 postimplantation. Alkaline phosphatase activity and cartilage mineralization were obliterated in lead-added plaques. However, calcium deposition was markedly enhanced in the lead-added plaques. Decreased alkaline phosphatase in Day 8 drinking water-lead plaques followed increased Day 12 drinking water lead plaque calcification. Enhanced cartilage calcification and reduced alkaline phosphatase activity in the drinking water-lead plaques was consistent with effects observed in the metaphyseal regions of bone in lead-exposed rats and pigs. The results of this study suggest that lead adversely influences bone development through disruption of mineralization during growth.
Alkaline Phosphatase↗
Review of international criteria and mixture rules for health hazard classification.
The presentation of consistent hazard information in the face of conflicting inter- and intranational regulations and standards is a formidable task. The principal challenge arises from the varying definitions of what is and is not a hazardous chemical and the differing rules that regulate the disclosure of components on material safety data sheets (MSDS) and labels. Some of the effects on hazard communication of nine health hazard classification systems of the United States, Canada, and the European Union are analyzed. The additional complication of differing rules that govern the hazard classification of mixtures is also discussed. The combination of inconsistent hazard classification of individual chemicals and dissimilar mixture rules can result in different conclusions about the hazard classification of commercial products. Faced with this situation, hazard communicators must focus on developing clear statements of the health effects that may arise from overexposure to a chemical, which is the essential purpose of developing MSDS and labels. These statements may be distinct from the terminology derived from the various classification systems. All national MSDS systems make provisions for including statements of hazard and also for providing the toxicology information that is the basis for translation into the locally governing classification terminology. Requirements for labels are often more restrictive, and the complete resolution of conflicting communication must await international harmonization of hazard classification systems including mixture rules.
Air Pollutants, Occupational↗
Racial differences in the occurrence of herpes zoster.
The purpose of this study was to determine if there are racial differences in the occurrence of herpes zoster (shingles). The study population was the Duke Established Populations for Epidemiologic Studies of the Elderly, a probability sample of community-dwelling persons > 64 years old in North Carolina. Interviewers administered a comprehensive health survey to the participants that included questions about lifetime occurrence of shingles. Of the 3206 subjects, 316 (9.9%) had had zoster: 81 (4.5%) of 1754 blacks and 235 (16.1%) of 1452 whites had had shingles (P < .0001). After controlling for age, cancer, and demographic factors, blacks remained one-fourth as likely as whites (adjusted odds ratio 0.25, 95% confidence interval 0.18-0.35; P = .0001) to have experienced zoster. In summary, blacks had a significantly lower risk of developing herpes zoster than whites, a new finding in herpes zoster epidemiology.
Age Factors↗
Expression of a murine cytomegalovirus early-late protein in "latently" infected mice.
Monoclonal antibodies were isolated from the spleen of a latently infected mouse to identify possible antigenic markers for latent murine cytomegalovirus infection. One antibody, AM3, was selected for further study. Characterization of the antigen recognized by AM3 confirmed that it is the early-late phosphoprotein pp50. The antigen was readily detected by immunoautoradiography in the spleens of acutely and latently infected mice. Low levels of the AM3/pp50 transcript were also detected in latently infected tissues by in situ hybridization. Presence of AM3/pp50 mRNA, as well as IE-1 transcripts, was confirmed by reverse transcription-polymerase chain reaction in 3 of 5 latently infected spleens. The expression of both immediate-early and early-late classes of viral genes suggests that persistent infection may be a component of the MCMV life cycle operationally defined as latency and that this gene is not specific for latency.
Animals↗
Mouse cytomegalovirus reactivation in severe combined immune deficient mice after implantation of latently infected salivary gland.
The hypothesis that replication-competent mouse cytomegalovirus (MCMV) is detectable in severe combined immunodeficient (scid) mice after implantation of latently infected tissue was examined. Sections of latently infected salivary gland from 5 BALB/c mice were implanted into 20 C.B-17 scid mice. Recipient scid mice were sacrificed weekly for 5 weeks, and MCMV infection was detected in target organs using culture and DNA polymerase chain reaction (PCR). All donors were negative by standard culture but positive by DNA PCR. Replicating MCMV was recovered from 9 of 15 recipient scid mouse salivary gland, lung, liver, or spleen samples at postoperative weeks 2-5. No virus was recovered from recipient scid mice at weeks 1 or 12. Transplantation of latently infected tissues into scid mice resulted in rapid reactivation and dissemination of the virus. Further study of this model promises insight into the mechanisms of CMV latency and reactivation.
Animals↗
Establishing standards and measurement methods for medical education.
This paper focuses largely on describing the accreditation system recently instituted for medical schools in Australia. Features of the system include evaluation of medical schools in terms of their own objectives and emphasis on the accreditation process as a consultation rather than an inspection. Steps in the accreditation process are as follows: briefing of the medical school, the school's preparation of a database on itself, a five-day assessment visit by a team of senior academics, immediate oral presentation of a preliminary report to the medical school, preparation of a written report, and awarding of accreditation for up to ten years. The paper also briefly describes the Community Based Education and Service (COBES) program, in which medical students at the University of Ilorin (in Nigeria) live, study, and work in villages for one month per year. The paper ends by noting the need to balance, on the one hand, defining and assessing those aspects of medical education important anywhere in the world and, on the other hand, addressing local context and relevance.
Accreditation↗
Structural equation modeling and nested ANOVA: effects of lead exposure on maternal and fetal growth in rats.
This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth.
Analysis of Variance↗
Effects of lead exposure on skeletal development in rats.
The effects of lead on growth in female rats and on growth and skeletal development in their offspring were investigated. No alteration in growth rate, compared to the growth rate in pair-fed controls, was observed in 48 weanling females continuously exposed to 250 or 1000 ppm lead in drinking water and fed a replete diet. After 49 days of exposure, all rats (24 pair-fed controls, 12 exposed to 250 ppm lead, and 12 exposed to 1000 ppm lead) were mated with control males. At parturition, six lactating dams each from the 250 and 1000 ppm lead groups were removed from lead exposure and given control drinking water, and six lactating dams each from the control group were given either 250 or 1000 ppm lead in drinking water. Exposure conditions for the remaining dams in the control, 250, and 1000 ppm groups were not changed. Maternal blood lead in the continuously lead-exposed groups was higher at the end of lactation than prior to mating. Lead exposure prior to parturition caused greater maternal tibial lead accumulation than lead exposure after parturition. In contrast, lead exposure prior to parturition had a lesser impact on offspring tibial lead accumulation than lead exposure after parturition. Decreases in tibial calcium and phosphorus were observed in dams exposed continuously to 250 or 1000 ppm lead; however, there was no apparent effect of lead on maternal growth-plate morphology or on growth-plate width. Offspring body weight was depressed relative to controls during suckling (Day 11) and after weaning (Day 24) in high-dose and continuously lead-exposed groups. Continuous lead exposure caused a greater decrease in offspring body weight than lead exposure only prior to or after parturition. Decreased tail length growth suggested possible effects of lead on tail vertebral bone growth. While tibial calcium and phosphorus levels were not changed in the weanlings, increased weanling growth-plate width, with disruption of chondrocyte organization, and wider metaphyseal trabeculae were observed. Although the mechanisms of these effects are not known, the results suggest that local lead-related effects on growth-plate chondrogenesis and metaphyseal mineralization may be involved.
Animals↗