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Biomedical subjects

F S Rhame

Publications and source records attributed to F S Rhame.

At least 19 recordsLinked to original sources

Preventing HIV transmission. Strategies to protect clinicians and patients.

Human immunodeficiency virus (HIV) transmission to healthcare workers arises primarily from percutaneous injury by sharp devices recently contaminated with infected blood. The danger is small but real, and substantial effort to reduce this risk is justified. The risk of transmission to patients from HIV-infected healthcare workers is much smaller. Attempts to accommodate measures to control this risk in standard protocols has engendered considerable debate. The discrimination and loss of insurability attendant to HIV infection also complicate the application of control measures. Where possible, procedures appropriate in cases involving known HIV infection should be applied in all situations. Acquiring tuberculosis from HIV-infected patients probably presents a greater hazard to healthcare workers than becoming infected with HIV itself.

Acquired Immunodeficiency Syndrome

Comparative pharmacokinetics of zidovudine in healthy volunteers and in patients with AIDS with and without hepatic disease.

To understand whether disease caused by the human immunodeficiency virus (HIV) affects zidovudine disposition, we compared the drug's pharmacokinetics in six healthy volunteers; six persons with the acquired immunodeficiency syndrome (AIDS) and no evidence of gastrointestinal (nausea, vomiting, diarrhea), renal (elevated blood urea nitrogen, serum creatinine), or hepatic (elevated liver function tests) disease; and three patients with AIDS and hepatic disease. After a single oral dose of zidovudine, serial blood samples were analyzed for drug concentration by radioimmunoassay. A one-compartment oral absorption model was fit to the concentration-time data. The absorption rate constant (4.05 vs 2.11 hr-1) and time to maximum concentration (0.61 vs 1.03 hr) were significantly different in healthy volunteers versus patients with AIDS without hepatic disease. Differences in half-life, oral clearance, and area under the curve were not statistically significant. In the three patients with AIDS plus hepatic disease, clearance was reduced an average of 63%, and area under the curve was increased by a factor of 2.3. These comparative pharmacokinetic data do not support profound differences between zidovudine's disposition in healthy volunteers and individuals with AIDS; however, the differences and trends that were observed may represent an effect of HIV disease. Although the presence of hepatic disease clearly indicates a need to modify individual dosages, these pharmacokinetic data may have more generalized implications for zidovudine dosing as the relationships between drug concentration and therapeutic or toxic effects are clarified.

Absorption

A look-back investigation of patients of an HIV-infected physician. Public health implications.

BACKGROUND: Transmission of the human immunodeficiency virus (HIV) to five patients receiving care from an HIV-infected dentist in Florida has recently been reported. Current data indicate that the risk of HIV transmission from health care workers to patients is low. Despite this low risk, programs to notify patients of past exposure to an HIV-infected health care worker are being conducted with increasing frequency. METHODS: We recently conducted an investigation of all the patients cared for by an HIV-infected family physician during a period when he had severe dermatitis caused by Mycobacterium marinum on his hands and forearms. After reviewing the patients' records, we notified 336 patients who had undergone one or more procedures (digital examination of a body cavity or vaginal delivery) placing them at potentially increased risk of HIV infection. The patients were offered tests for HIV infection and counseling. RESULTS: Of the 336 patients, 325 (97 percent) had negative tests for HIV antibody, 3 (1 percent) refused testing, 1 (less than 1 percent) died of a cause unrelated to HIV infection before notification, and the HIV-antibody status of 7 (2 percent) remained unknown. The direct and indirect public health costs of this investigation were approximately $130,000. CONCLUSIONS: The results of this investigation raise important questions about the risk of HIV transmission from health care workers to patients and the usefulness of HIV look-back programs, particularly in the light of recently published recommendations from the Centers for Disease Control. We propose that before a look-back investigation is undertaken, there should be a clearly identifiable risk of transmission of the infection, substantially higher than the risk requiring limitation of an HIV-infected health care worker's practice prospectively.

AIDS Serodiagnosis

Prevention of nosocomial aspergillosis.

Unfiltered outside air averages 1-15 pathogenic Aspergillus sp. colony forming units (cfu) m-3 although short-term fluctuations are substantial. Seasonal variation reflects increased spore prevalence during periods of greater availability of non-viable matter. In hospital, airborne spores reflect incomplete filtration, infiltration of outside air and shedding of adherent spores from introduced objects. In highly protected hospital areas supplied with air filtered at high efficiency, where aspergillus cfus may be as low as 0.01 cfu m-3, infiltration and shedding contribute a high fraction of ambient spores. Nosocomial aspergillosis occurs in linear proportion to the mean ambient hospital airborne spore content. An analysis presuming a steady-state dynamic equilibrium is imperfect because repeated sampling produces occasional high counts which violate a Poisson distribution. 'Mini-bursts' arise from disturbance of settled spores in dust, shedding spores from clothes or other subtle sources. These sources are best mitigated by increasing the air change rate. It is most important to protect bone marrow transplant patients, leukaemia and lymphoma patients undergoing intensive, potentially curative therapy. The optimal protective environments include high filtration efficiency, point-of-use filters, protection against infiltration and filter bypass, elimination of in-hospital sources, and high air change rates.

Air Microbiology

The epidemiology of classic, African, and immunosuppressed Kaposi's sarcoma.

The etiology of Kaposi's sarcoma remains somewhat obscure. While lesions of classic Kaposi's sarcoma, African Kaposi's sarcoma, and immunosuppressed Kaposi's sarcoma have been found to be indistinguishable from one another, the reasons for the variations in type and severity have not been established. The origin of the spindle cell is yet to be agreed on. Geographic variation does not seem as important as ethnic variation. The very young and the very old, perhaps two ages of weakened immunity, tend to have a higher incidence of Kaposi's sarcoma. Children and AIDS patients tend to develop more virulent disease. Males tend to get Kaposi's sarcoma at higher rates than do females. Jewish and Mediterranean males have the highest incidence of classic Kaposi's sarcoma, and African Bantu have the highest incidence of African Kaposi's sarcoma, classifications which do not apply to the Kaposi's sarcoma population in the United States. Male homosexuals have much higher incidence of Kaposi's sarcoma than do male heterosexuals, but since the early 1980s, its incidence as the presenting manifestation of AIDS has decreased dramatically. There is no unequivocal association with HLA haplotype (though DR5 carriers may be at especially high risk) or evidence of family clustering. There is an impressive but not always consistent association between Kaposi's sarcoma development and immunodeficiency. Environmental factors, such as nitrite use, immunosuppression, and repeated cytomegalovirus infection, are associated with Kaposi's sarcoma, but the exact mechanism is unclear and the associations remain inconsistent. Finally, it is still unclear if there is a causative infectious agent for Kaposi's sarcoma. While cytomegalovirus has been linked to Kaposi's sarcoma, there are weaknesses in its hypothetical role as an etiologic agent as is the case for HIV itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome

Quantitative I-123-IMP brain SPECT and neuropsychological testing in AIDS dementia.

We performed I-123-IMP SPECT brain imaging on seven mildly demented AIDS patients and seven normal subjects. In an attempt to detect and quantitate regions of decreased I-123-IMP uptake, pixel intensity histograms of normalized SPECT images at the basal ganglia level were analyzed for the fraction of pixels in the lowest quartile of the intensity range. This fraction (F) averaged 17.5% (S.D. = 4.6) in the AIDS group and 12.6% (S.D. = 5.1) in the normal group (p less than .05). Six of the AIDS patients underwent neuropsychological testing (NPT). NPT showed the patients to have a variety of mild abnormalities. Regression analysis of NPT scores versus F yielded a correlation coefficient of .80 (p less than .05). We conclude that analysis of I-123-IMP SPECT image pixel intensity distribution is potentially sensitive in detecting abnormalities associated with AIDS dementia and may correlate with the severity of dementia as measured by NPT.

AIDS Dementia Complex

Periodontal status of individuals in early stages of human immunodeficiency virus infection.

The purpose of this study was to evaluate the association of periodontal health and human immunodeficiency virus infection among individuals in the early stages of disease who were participating in randomized placebo-controlled clinical trials of zidovudine. Previous reports have described a rapidly progressive periodontitis and atypical gigivitis associated with late stages of infection by the human immunodeficiency virus. A health history was completed by each subject. Baseline oral examinations were completed on 97 asymptomatic patients and nine with AIDS-related complex (ARC) during their regular clinic visit. Follow-up examinations were conducted at 3-month intervals throughout the 48 weeks of the oral study. Evaluations of plaque, calculus, gingival abnormalities, caries, and periodontal disease were conducted. Periodontal measurements included plaque index (PI), gingival index (GI), bleeding index (BI), probing depth (PD), and observation for cratering, necrosis, and tooth mobility on six teeth in each patient. More than half of the subjects had visited their dentist during the previous year and had had an oral prophylaxis; less than 25% of them had had either restorative work or extractions. The mean scores for periodontal indices averaged over the course of the study in asymptomatic and ARC respectively were: PI: 0.9 (SE 0.04) and 0.9 (SE 0.08), 0.818; GI: 1.0 (SE 0.04) and 0.9 (SE 0.07), P = 0.412; BI: 0.6 (SE 0.04) and 0.4 (SE 0.07), P = 0.278; PD: 2.9 (SE 0.05) and 2.6 (SE 0.10), P = 0.140. There was no evidence of cratering, necrosis, or tooth mobility in either group. Few had calculus or dental caries. There were no clinically significant differences detected between ARC versus asymptomatic patients. Dental histories and oral examinations showed that two groups of patients in early stages of HIV-disease were in good periodontal health.

AIDS-Related Complex

Nosocomial transmission of respiratory syncytial virus in immunocompromised adults.

Respiratory syncytial virus (RSV) isolates obtained from nine infected immunocompromised adult patients hospitalized during two consecutive winters (January through April 1987 and 1988) were collected and analyzed against a panel of monoclonal antibodies by an enzyme immunoassay. The history of the patients' illness, onset of symptoms, and date of initial isolation of virus was correlated with the hospital ward and time of hospitalization. Three patients died of respiratory failure related to RSV infection acquired nosocomially. A cluster of RSV disease in four patients hospitalized simultaneously during the 1987 season was demonstrated to be caused by four antigenically distinct viruses; despite an epidemiologic link among the patients, each had been infected from a different source. The RSV disease in the five immunocompromised adults in 1988 was caused by two distinct strains; three patients were infected with RSV subgroup A/4, and two were infected with RSV subgroup B/2. Combining the epidemiologic and strain characterization studies, none of four patients in 1987 were infected from each other, and two of five patients in 1988 may have been infected, directly or indirectly, from one of the other five. The strain characterization studies demonstrated the potential complexity of RSV nosocomial transmission and the need to consider a number of sources for transmission in developing effective prevention strategies. The three deaths underscore the importance of nosocomial RSV disease and the importance of effective prevention strategies.

Adult

Increasing CD8+ T lymphocytes predict subsequent development of intraoral lesions among individuals in the early stages of infection by the human immunodeficiency virus.

Determining the progression of human immunodeficiency virus (HIV) type 1 infection based on cellular and clinical markers has become increasingly important. Although a number of studies have shown a relationship between the presence of certain oral lesions and progression to AIDS, few data exist regarding the association with T lymphocyte counts. In this study, the question of whether intraoral lesions preceded or were the consequences of changes in T lymphocyte counts was examined. A total of 116 HIV-infected patients participating in two randomized double-blind placebo-controlled trials of zidovudine at the University of Minnesota AIDS Clinical Trials Unit (ACTU) were enrolled in a prospective dental study. Patients were examined for the presence of hairy leukoplakia, candidiasis, herpes simplex, herpes zoster, aphthae, atypical gingivitis, HIV-associated periodontitis, and necrotizing ulcerative gingivitis, as well as other oral lesions, every 3 months for a maximum of four examinations over a 1-year period. T lymphocyte counts before and after each patient's oral examination were obtained. No significant differences were found at examination 1 for differences in gender, race, age, education, tobacco smoking status, ethanol consumption habits, duration in ACTU drug protocol, duration in dental study protocol, or mean T lymphocyte counts between individuals with or without oral lesions at any time in the dental study.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking

An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related complex.

AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent.

AIDS-Related Complex

Human immunodeficiency virus type 1 detected in all seropositive symptomatic and asymptomatic individuals.

Between February 1987 and October 1988, peripheral mononuclear blood cells (PBMC) from 409 adult individuals antibody positive by Western (immuno-)blot for human immunodeficiency virus type 1 (HIV-1) (56 acquired immunodeficiency syndrome [AIDS] patients, 88 patients with AIDS-related complex, and 265 asymptomatic individuals) were consecutively cultured for HIV-1 or tested for the presence of HIV-1 DNA sequences by a polymerase chain reaction assay (PCR). We isolated HIV-1 or detected HIV-1 DNA sequences from the PBMC of all 409 HIV-1 antibody-positive individuals. None of 131 healthy HIV-1 antibody-negative individuals were HIV-1 culture positive, nor were HIV-1 DNA sequences detected by PCR in the blood specimens of 43 seronegative individuals. In addition, HIV-1 PCR and HIV-1 culture were compared in testing the PBMC of 59 HIV-1 antibody-positive and 20 HIV-1 antibody-negative hemophiliacs. Both methods were found to have sensitivities and specificities of at least 97 and 100%, respectively. In contrast, the sensitivities of serum HIV-1 antigen testing in AIDS patients and asymptomatic seropositive patients were 42 and 17%, respectively. Our ability to directly demonstrate HIV-1 infection in all HIV-1 antibody-positive individuals provides definitive support that HIV-1 antibody positivity is associated with present HIV-1 infection. Moreover, the sensitivities and specificities of PCR and culture for the detection of HIV-1 appear to be equivalent, and both methods are superior to testing for HIV-1 antigen in serum for the direct detection of HIV-1.

AIDS-Related Complex

Effect of oral dextran sulfate on the mouse intestinal tract.

Oral dextran sulfate is associated with adverse intestinal effects, including severe diarrhea, in some AIDS patients. We therefore investigated the intestinal flora and the intestinal histology of mice given drinking water supplemented with 8 mg/ml of dextran sulfate. There were no noticeable alterations in the major groups of intestinal bacteria in mice given oral dextran sulfate for 7 days. Likewise, there was no abnormal pathology in the ilea or colons of mice treated for 7 days with oral dextran sulfate. However, after 21 and 38 days, there was a noticeable overgrowth of facultative gram-negative bacilli in the colonic and cecal flora of dextran sulfate-treated mice. This overgrowth appeared to be due to bacterial species in the family Enterobacteriaceae, primarily Escherichia coli. Bacterial overgrowth was accompanied by mild histological alterations in the intestinal mucosa, i.e., blunting of ileal villi and colonic crypts, with mild epithelial cell dysplasia. Thus, oral dextran sulfate was associated with quantitative changes in the mouse intestinal flora, as well as histological changes in the intestinal mucosa.

Animals

Performance characteristics of serologic tests for human immunodeficiency virus type 1 (HIV-1) antibody among Minnesota blood donors. Public health and clinical implications.

STUDY OBJECTIVE: To evaluate performance characteristics of sequential enzyme immunoassay (EIA) and Western blot human immunodeficiency virus type 1 (HIV-1) antibody testing in a low-risk population. DESIGN: Three-year prospective study of a selected sample from a community-based population. SETTING: Two blood collection facilities in Minnesota. POPULATION: Minnesota blood donors. RESULTS: During the study period, 630,190 units of blood (donations) from an estimated 290,110 Minnesota-resident donors were screened for HIV-1 antibody. Seventeen Minnesota-resident donors were identified as positive for HIV-1 antibody. Sixteen donors were available for follow-up HIV-1 culture: all were culture positive. The other donor, who was not available for follow-up culture, was likely infected with HIV-1 based on a history of high-risk behavior and positive serologic findings for hepatitis B surface antigen. Using 95% binomial confidence intervals, performance characteristics for sequential EIA and Western blot HIV-1 antibody serology were as follows: false-positive rate by number of donations, 0% to 0.0006%; specificity by number of donations, 99.9994% to 100%; predictive value of a positive test, 81% to 100%. CONCLUSIONS: In this low-risk population, the false-positive rate of serologic tests for HIV-1 antibody, using HIV-1 culture as the definitive standard for infection status, was extremely low and test specificity was extremely high.

AIDS Serodiagnosis