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Biomedical subjects

J D Hamilton

Publications and source records attributed to J D Hamilton.

At least 19 recordsLinked to original sources

A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study.

BACKGROUND: Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established. METHODS: We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed. RESULTS: During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash. CONCLUSIONS: In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

Acquired Immunodeficiency Syndrome

Aging and reactivation of latent murine cytomegalovirus.

BALB/c mice were experimentally infected with murine cytomegalovirus (MCMV) to discover whether latent MCMV persisted in aging mice and to examine the effect of aging on MCMV reactivation. Latently infected mice received saline, cyclophosphamide, or allogeneic blood at 6 and 18 months of age. MCMV DNA was detected by polymerase chain reaction in submaxillary salivary gland biopsy specimens from saline-treated young and old mice. Evidence of MCMV reactivation was sought by culture of biopsy specimens and by MCMV IgG ELISA of pre- and posttreatment sera from all animals. Very few cyclophosphamide- or saline-treated mice reactivated MCMV at either age, but young transfused mice reactivated MCMV significantly more often than did old transfused mice. These experiments indicate that MCMV DNA persists in the salivary gland of aging mice but that the likelihood of MCMV reactivation does not increase with age.

Aging

Murine cytomegalovirus gene amplification and culture after submaxillary salivary gland biopsy.

An important target tissue for murine cytomegalovirus (CMV) infection is the submaxillary salivary gland. Submaxillary salivary gland biopsy specimens from BALB/c mice latently infected with murine CMV were examined for murine CMV DNA by in vitro enzymatic amplification using the polymerase chain reaction preceding oligonucleotide hybridization. The amplified sequence was a 152-base pair segment from within the immediate early gene of murine CMV. Biopsy and whole gland specimens from acutely infected BALB/c mice and latently infected, immunosuppressed BALB/c mice were compared for active murine CMV infection. After acute infection with murine CMV, virus was recovered in all cultures of both biopsy and whole salivary gland specimens but from none of the latently infected animals. Reactivated virus was detected by culture of both biopsy (90%) and whole salivary gland specimens (100%) from latently infected mice that received antithymocyte serum. Viral nucleic acid was detected in 90% of biopsy specimens from latently infected animals. Hence, active murine CMV infection can be detected in biopsy specimens from mice with acute and reactivated infection and murine CMV DNA can be amplified and detected in salivary gland biopsy specimens from latently infected animals. Biopsy of this or other target tissues can be useful for obtaining tissue for viral studies where the survival of the animal is important and it is useful to distinguish latent from acute or reactivated infection.

Animals

The accreditation of undergraduate medical education in Australia.

The Australian Medical Council was established in 1985 with one of its three functions being the accreditation of medical schools and of courses leading to basic medical qualifications. The Accreditation (Standing) Committee has developed guidelines for assessment and accreditation in Australia, and commenced its programme of visits to Australian medical faculties in March 1988, with the tenth faculty scheduled to be visited in September 1993. This article describes the process of assessment and accreditation developed in Australia by the Australian Medical Council. A later article will discuss the issues in medical education that have been identified during the process of accreditation.

Accreditation

Persistence of antibody in healthcare workers vaccinated against hepatitis B.

A cross-sectional serological survey was undertaken in 82 randomly selected high-risk healthcare workers previously vaccinated with the hepatitis B vaccine. The study design allowed for the identification and testing for hepatitis B surface antibody in equal numbers of employees in six-month intervals up to five years after vaccination. The results showed a consistent decline in antibody level with time, and an increasing proportion of participants with antibody levels below the commonly accepted protective level of greater than or equal to 10 S/N (sample counts/negative control counts) radioimmunoassay units. The percent of vaccinees whose S/N ratio was greater than 10 fell from 10% at one year, to 25% at two years, to over 50% at four years. Based on these figures, as well as the financial costs of hepatitis B in employees and the predictability of booster immunization, it was possible to assess the cost benefit of a hospital policy for reimmunization. At our institution, a strategy of revaccination at fixed intervals could save up to $200,000 over a ten-year period if revaccination was not offered and vaccine efficacy declined. The information obtained should help determine the need for revaccination and the advantages and disadvantages of alternative revaccination strategies.

Adult

Detection of mouse cytomegalovirus nucleic acid in latently infected mice by in vitro enzymatic amplification.

Transmission of human and murine cytomegalovirus (CMV) with transfusions and organ transplantation suggests that the latent virus is located in multiple organs and perhaps multiple cell types. The direct identification and localization of the latent virus in the normal host has been difficult using standard culture and hybridization techniques. In vitro amplification using the polymerase chain reaction followed by oligonucleotide hybridization can be used to detect murine CMV DNA. When this method was applied to DNA extracted from latently infected mice, it allowed detection of viral nucleic acid not detected by standard Southern hybridization. The results of these studies support the presence of latent murine CMV in multiple organs including the salivary gland, spleen, and kidney. Amplification and detection of viral DNA in purified renal tubule preparations suggest that this may be a site of viral latency and potential source of the virus during renal transplantation.

Animals

Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease.

The polymerase chain reaction (PCR) was used to detect human immunodeficiency virus type 1 (HIV-1) proviral sequences (gag and env) in nucleated cells from the cerebrospinal fluid (CSF) of 31 HIV-1-positive patients, and the results were compared with clinical and radiologic evidence of neurologic disease. Provirus was detected in 21 patients, of whom 20 had neurologic abnormalities. Provirus was not detected in another 6, all of whom were neurologically normal. No neurologic disease has developed in 4 of these 6 patients for whom 12.8 months of follow-up is available. PCR of CSF nucleated cells from HIV-positive patients provides early, rapid, direct evidence of neurologic involvement.

AIDS Dementia Complex

Medical education in China for the 21st century: the context for change.

A national conference on Medical Education in China for the 21st Century was convened in Beijing in November 1986. Over 6 days, leading medical educators and Ministry of Public Health officials from across China presented China's future health service needs and debated opportunities and constraints in meeting those needs by various innovations in medical education. Recent political upheavals have left many educators wary of innovation. There are major, conflicting demands between the needs of rural primary care service and the needs of medical schools to replenish medical school professional ranks depleted by the Cultural Revolution. Multiple and varied experiments in medical education will be encouraged among China's medical schools. China will probably amalgamate indigenous and foreign education experiments, offering the world community new and important innovations in medical education.

China

Withholding medical treatment from the severely demented patient. Decisional processes and cost implications.

We performed an observational study to determine the prevalence of severe dementia in a general medicine unit, the categories of acute medical care provided to these patients, the process by which treatment decisions are made, and their cost implications. The prevalence of severe dementia was 4.4%. The patients from whom some form of acute medical care was withheld (26 [45.6%] of 57) were more severely ill at admission and had a mortality rate five times higher than those who received full care. Physicians cited family wishes in 75.9% of the decisions to limit care but in only 10.9% of the decisions to give full care. The only differences in charges incurred were due to differential mortality rates in individuals from whom care was withheld. We recommend that hospitals develop and implement protocols for decision making in the care of the severely demented to promote open discussions among providers and families and to increase family contributions to decision making. We believe that the extension of this consultative approach to decisions involving severely demented patients may have the virtue of combining more humane care with more cost-effective care.

Acute Disease