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Biomedical subjects

D H Osmond

Publications and source records attributed to D H Osmond.

At least 19 recordsLinked to original sources

A 13-year molecular epidemiological analysis of tuberculosis in San Francisco.

BACKGROUND: We examined the molecular epidemiology of tuberculosis (TB) in San Francisco during a 13-year period encompassing the peak of TB resurgence and subsequent decline to historic low levels. OBJECTIVE: To compare rates of TB caused either by rapid progression of recent Mycobacterium tuberculosis infection or by reactivation of latent infection. METHODS: All TB cases reported from 1991 to 2003 were included. Genotyping was performed to identify clustered cases. RESULTS: The annual TB case rate decreased significantly from 50.8 to 28.8 cases/100000 persons from 1992 to 1999 (P < 0.0001). After 1999, no significant decrease was observed for the population as a whole or in any subgroup examined. Similarly, the rate of clustered cases decreased significantly from 1992 to 1999 (11.4 to 3.1 cases/100000, P < 0.0001). Although the rate of non-clustered cases also declined significantly (25.6 to 17.6 cases/100,000, P < 0.0001), there was a disproportionate reduction in clustered cases (94.7% vs. 50.8%, P < 0.0001). Neither clustered nor non-clustered cases decreased significantly after 1999. CONCLUSIONS: TB case rates reached a plateau despite ongoing application of control measures implemented in 1993. These data suggest that intensification of measures designed to identify and treat persons with latent TB infection will be necessary to further reduce TB incidence.

Cluster Analysis↗

Correlates of heavy substance use among young gay and bisexual men: The San Francisco Young Men's Health Study.

Correlates of heavy substance use among a household-based sample of young gay and bisexual men (n=428) were identified and the odds ratio (OR) was calculated. A total of 13.6% reported frequent, heavy alcohol use and 43% reported polydrug use. Compared with men employed in professional occupations, men in service positions (OR=3.77) and sales positions (OR=2.51) were more likely to be heavy alcohol consumers. Frequent gay bar attendance and multiple sex partners were related to heavy alcohol use, as well as to polydrug use. Polydrug users were more likely to be HIV seropositive (OR=2.05) or of unknown HIV serostatus (OR=2.78). HIV serostatus was similarly related to frequent drug use. These correlates of heavier substance use among young gay and bisexual men could be used to identify and intervene early with members of this population who are at risk of substance misuse, as well as HIV/AIDS risk.

Adolescent↗

Primary care physicians' experience with disease management programs.

OBJECTIVE: To examine primary care physicians' perceptions of how disease management programs affect their practices, their relationships with their patients, and overall patient care. DESIGN: Cross-sectional mailed survey. SETTING: The 13 largest urban counties in California. PARTICIPANTS: General internists, general pediatricians, and family physicians. MEASUREMENTS AND MAIN RESULTS: Physicians' self-report of the effects of disease management programs on quality of patient care and their own practices. Respondents included 538 (76%) of 708 physicians: 183 (34%) internists, 199 (38%) family practitioners, and 156 (29%) pediatricians. Disease management programs were available 285 to (53%) physicians; 178 had direct experience with the programs. Three quarters of the 178 physicians believed that disease management programs increased the overall quality of patient care and the quality of care for the targeted disease. Eighty-seven percent continued to provide primary care for their patients in these programs, and 70% reported participating in major patient care decisions. Ninety-one percent reported that the programs had no effect on their income, decreased (38%) or had no effect (48%) on their workload, and increased (48%)) their practice satisfaction. CONCLUSIONS: Practicing primary care physicians have generally favorable perceptions of the effect of voluntary, primary care-inclusive, disease management programs on their patients and on their own practice satisfaction.

Chi-Square Distribution↗

Friend or foe? How primary care physicians perceive hospitalists.

BACKGROUND: Increased use of hospitalists is redefining the role of primary care physicians. Whether primary care physicians welcome this transition is unknown. We examined primary care physicians' perceptions of how hospitalists affect their practices, their patient relationships, and overall patient care. METHODS: A mailed survey of randomly selected general internists, general pediatricians, and family practitioners with experience with hospitalists practicing in California. MAIN OUTCOME MEASURES: Physicians' self-reports of hospitalists' effects on quality of patient care and on their own practices. RESULTS: Seven hundred eight physicians were eligible for this study, and there was a 74% response rate. Of the 524 physicians who responded, 34% were internists, 38% were family practitioners, and 29% were pediatricians. Of the 524 respondents, 335 (64%) had hospitalists available to them and 120 (23%) were required to use hospitalists for all admissions. Physicians perceived hospitalists as increasing (41%) or not changing (44%) the overall quality of care and perceived their practice style differences as neutral or beneficial. Twenty-eight percent of primary care physicians believed that the quality of the physician-patient relationship decreased; 69% reported that hospitalists did not affect their income; 53% believed that hospitalists decreased their workload; and 50% believed that hospitalists increased practice satisfaction. In a multivariate model predicting physician perceptions, internists, physicians who attributed loss of income to hospitalists, and physicians in mandatory hospitalist systems viewed hospitalists less favorably. CONCLUSIONS: Practicing primary care physicians have generally favorable perceptions of hospitalists' effect on patients and on their own practice satisfaction, especially in voluntary hospitalist systems that decrease the workload of primary care physicians and do not threaten their income. Primary care physicians, particularly internists, are less accepting of mandatory hospitalist systems. Arch Intern Med. 2000;160:2902-2908

Attitude of Health Personnel↗

Obtaining HIV test results with a home collection test kit in a community telephone sample.

OBJECTIVES: To test the feasibility of obtaining HIV test results by home collection kit from a probability telephone sample of men who have sex with men (MSM). METHODS: A quota sample of 615 MSM previously interviewed by the Urban Men's Health Study phone survey in Chicago, Los Angeles, New York City, and San Francisco were re-contacted and offered an HIV test using an oral specimen (Orasure) home collection kit. RESULTS: Eighty percent consented to be mailed a kit, and 84% returned a specimen, for a 67% participation rate. All self-reported HIV-positive persons tested positive (77 of 77); 4 of 266 (1.5%) with a prior negative test and 2 of 69 (2.9%) with no prior positive HIV test result. Participation was associated with self-reported prior HIV test status-HIV-positive (83%), HIV-negative (68%), or no prior HIV test result (54%)-and marginally associated with New York City residence after adjustment for HIV status (odds ratio = 0.7; 95% confidence interval, 0.4-1.1; p =.08). CONCLUSIONS: These results suggest that urban MSM identified and interviewed by telephone will participate in home collection HIV testing. This methodology could be used to produce population-based estimates of HIV seroprevalence and seroincidence in MSM and could probably be extended to other populations and other viral infections.

AIDS Serodiagnosis↗

Invited commentary: determining specific sexual practices associated with human herpesvirus 8 transmission.

Laboratory and epidemiologic studies have established human herpesvirus 8 (HHV8) as an etiologic agent of Kaposi's sarcoma. With strong evidence linking HHV8 infection with the number of sexual partners among homosexual men, the challenge now is to determine the specific sexual acts associated with HHV8 transmission. Initial studies of specific practices, however, have differed in their conclusions; the paper by Dukers et al. in this issue of the Journal is the first to associate penile-oral intercourse with HHV8 transmission. Many sources of bias may contribute to the conflicting findings of studies reported to date: HHV8 research still lacks an adequately specific and sensitive serologic assay; identification of relevant exposure periods and measurement of sexual practices are imperfect; and sufficient adjustment for confounding is problematic. These numerous potential biases may be particularly important when trying to detect underlying associations that may be of low-order magnitude. The study by Dukers et al. (Am J Epidemiol 2000;151:213-24) is an important contribution to research on HHV8 transmission, but we do not yet know enough about the possible sexual routes of transmission to recommend avoiding any single behavior. For now, the best prevention advice is to reinforce the more general safe sex practices that have been promoted to prevent human immunodeficiency virus and other sexually transmitted diseases.

Herpesviridae Infections↗

Characterization of apelin, the ligand for the APJ receptor.

The apelin peptide was recently discovered and demonstrated to be the endogenous ligand for the G protein-coupled receptor, APJ. A search of the GenBank databases retrieved a rat expressed sequence tag partially encoding the preproapelin sequence. The GenBank search also revealed a human sequence on chromosome Xq25-26.1, containing the gene encoding preproapelin. We have used the rat sequence to screen a rat brain cDNA library to obtain a cDNA encoding the full-length open reading frame of rat preproapelin. This cDNA encoded a protein of 77 amino acids, sharing an identity of 82% with human preproapelin. Northern and in situ hybridization analyses revealed both human and rat apelin and APJ to be expressed in the brain and periphery. Both sequence and mRNA expression distribution analyses revealed similarities between apelin and angiotensin II, suggesting they that share related physiological roles. A synthetic apelin peptide was injected intravenously into male Wistar rats, resulting in immediate lowering of both systolic and diastolic blood pressure, which persisted for several minutes. Intraperitoneal apelin injections induced an increase in drinking behavior within the first 30 min after injection, with a return to baseline within 1 h.

Amino Acid Sequence↗

Use of epidemiologically well-defined subjects and existing immunofluorescence assays to calibrate a new enzyme immunoassay for human herpesvirus 8 antibodies.

Agreement between assays for the detection of human herpesvirus 8 (HHV-8) antibodies has been limited. In part, this disagreement has been because assay calibration (i.e., differentiating positive from negative results) has not been done in a standardized fashion with reference to a wide spectrum of HHV-8-infected (true-positive) and HHV-8-uninfected (true-negative) persons. To describe the performance of an assay for HHV-8 antibodies more accurately, we used epidemiologically well-characterized subjects in conjunction with testing on two existing immunofluorescence assays for HHV-8 antibodies to define two groups: a group of 135 HHV-8-infected individuals (true positives), including Kaposi's sarcoma patients and those asymptomatically infected, and a group of 234 individuals with a high likelihood of being HHV-8 uninfected (true negatives). A new enzyme immunoassay (EIA), using lysed HHV-8 virion as the antigen target, was then developed. With the above true positives and true negatives as references, the sensitivity and specificity of the EIA associated with different cutoff values were determined. At the cutoff that maximized both sensitivity and specificity, sensitivity was 94% and specificity was 93%. When the EIA was used to test a separate validation group, a distribution of seropositivity that matched that predicted for the agent of Kaposi's sarcoma was observed: 55% of homosexual men were seropositive, versus 6% seropositivity in a group of children, women, and heterosexual men. It is proposed that the EIA has utility for large-scale use in a number of settings and that the calibration method described can be used for other assays, both to more accurately describe the performance of these assays and to permit more-valid interassay comparison.

Antibodies, Viral↗

Name-based surveillance and public health interventions for persons with HIV infection. Multistate Evaluation of Surveillance for HIV Study Group.

Name-based surveillance of HIV infection is the law in 31 U.S. states but remains controversial. This policy can be advocated solely to support surveillance of the epidemic, but a frequent argument is that it also provides a public health benefit by allowing follow-up of HIV-infected persons. These persons can then receive timely medical care and can be assisted with notifying sex and needle-sharing partners. Few comparative data are available to evaluate the outcomes of these interventions. In five states with name-based surveillance of HIV infection, the Multistate Evaluation of Surveillance for HIV Study Group surveyed a cross-sectional probability sample of persons with AIDS who tested positive for HIV before the date of their AIDS diagnosis. Health department follow-up of a reported HIV infection was not associated with more timely receipt of medical care after a positive HIV test result. Only 8.6% of persons who delayed medical care after their first positive HIV test result gave concern about being reported by name as a reason; no person gave it as the main reason. Persons who were tested anonymously and those who were tested confidentially did not differ in the mean number of sex and needle-sharing partners notified: Those tested anonymously reported personally notifying 3.85 sex and needle-sharing partners, and those tested confidentially reported notifying-personally and through the health department-3.80 partners. Many researchers and policymakers believe that name-based surveillance of HIV infection will have positive or negative effects on partner notification and access to health care. These results suggest that the potential for such effects has been exaggerated.

Anonymous Testing↗

Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status.

OBJECTIVE: To examine patterns and factors that correlate with unprotected anal intercourse (UAI) practices among San Francisco gay men, including UAI with partners of unknown or different HIV antibody status. DESIGN: A longitudinal cohort recruited for the San Francisco Young Men's Health Study in 1992; re-assessed annually. PARTICIPANTS AND METHODS: A sample of 510 unmarried gay men who were 18 to 29 years at baseline were originally recruited as part of a larger population and referral-based sample. Subjects participated in four consecutive waves of data collection. RESULTS: The prevalence of reported unprotected anal intercourse (UAI) increased from 37% to 50% between 1993-1994 and 1996-1997. Almost half of all men who reported UAI in 1996-1997 indicated that it occurred with a partner of unknown or discordant HIV antibody status. This high-risk practice correlated with greater numbers of male sex partners, use of nitrite inhalants, sex in commercial sex environments, perceived difficulty controlling sexual risk-taking, and negative emotional reactions following UAI. CONCLUSIONS: These data on increasing rates of sexual risk-taking further confirm trends in sexual behavior previously suggested by rising rates of rectal gonorrhea in this population. Additional and sustained prevention efforts are urgently needed in light of the very high background rates of HIV infection found among gay men in San Francisco.

Adult↗

Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.

AIDS-Related Opportunistic Infections↗

Kaposi's sarcoma-associated herpesvirus and sexual transmission of cancer risk.

The epidemiology of AIDS-related Kaposi's sarcoma (KS) predicted that a nonubiquitous sexually transmitted agent was central to its etiology. An assessment of Hill's criteria for causality reveals there is now sufficient evidence to declare Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, a necessary, albeit not sufficient, cause of KS. The most compelling evidence comes from longitudinal studies presented in the past year that demonstrate that KSHV infection temporally precedes and is independently associated with AIDS-related KS even after adjustment for other potential etiologic factors. In the United States and Northern Europe, many studies have now shown that KSHV can be sexually transmitted among homosexual men, but determining specific routes of sexual transmission is methodologically challenging, and initial results are conflicting. Data are also emerging that demonstrate nonsexual modes of transmission. Spread via renal allograft appears to occur, and in endemic areas of Europe and Africa, nonsexual horizontal and perhaps vertical spread are the dominant modes of transmission.

Herpesviridae Infections↗

Sexual transmission and the natural history of human herpesvirus 8 infection.

BACKGROUND: Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history. METHODS: The San Francisco Men's Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposi's sarcoma. RESULTS: Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposi's sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners. CONCLUSIONS: The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposi's sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually transmitted among men.

AIDS-Related Opportunistic Infections↗

Potent 'new pressor protein' related to coagulation factor XII is potentiated by inhibition of angiotensin converting enzyme.

BACKGROUND: 'New pressor protein' was observed after tryptic activation of human and rat plasma in vitro, which is done conventionally for prorenin measurements. RESULTS: It is potently pressor, heat labile, possesses enzyme activity, and has a relative molecular mass > 30 kDa with isoelectric point(s) 4.7-4.9. New pressor protein equivalent to only 0.01 ml human, or rat, plasma injected intravenously quickly raises systolic blood pressure in 300 g anesthetized, ganglion-blocked, bioassay rats by about 15 mmHg. For unknown reasons, this is potentiated to about 45 mmHg after treatment with angiotensin I converting enzyme inhibitors (such as captopril and enalapril). New pressor protein activity in rats remains normal 24 h after bilateral nephrectomy, suggesting that it has an extrarenal origin and, furthermore, excluding the possibility of an association with renin-angiotensin system. Systolic blood pressure elevation is greater than the diastolic one, implicating cardiotonic effects. Human plasma new pressor protein was purified using standard biochemical techniques and its N-terminal sequence (19 residues) found to be homologous with the beta factor XIIa fragment of coagulation factor XII. This was supported by demonstrating inhibition of new pressor protein activity in vitro using the factor XII-specific corn trypsin inhibitor. Also, human new pressor protein activity in humans congenitally deficient in coagulation factor XII is very low. The high potency and multiphasic, cardiotonic effects of injected new pressor protein suggest that it interacts synergistically with other systems in the body. This was confirmed by showing that, within 10 min of total bilateral adrenalectomy, responses to new pressor protein decreased markedly. CONCLUSIONS: New pressor protein's action requires adrenal (medullary?) involvement, but its mechanism of action and that of its potentiation by angiotensin converting enzyme inhibitors remain unknown. The physiologic and clinical relevance of these observations depends on whether activation of new pressor protein can occur in vivo.

Adrenal Medulla↗

Treatment of X-linked hereditary nephritis in Samoyed dogs with angiotensin converting enzyme (ACE) inhibitor.

X-linked hereditary nephritis (HN) in Samoyed dogs is a model for human HN (Alport's syndrome). Angiotensin converting enzyme (ACE) inhibitors have been shown to slow the progression of renal disease in animal models and human patients. To determine the effect of ACE inhibitor treatment on X-linked HN in Samoyed dogs, a group of affected and a group of normal males were each randomly divided into two subgroups, which were either treated with an ACE inhibitor or left untreated. ACE inhibitor treatment caused significant increases (P < 0.05) in plasma renin activity in normal and affected dogs, confirming its effectiveness, but did not lower systemic blood pressure. Three of four affected treated dogs had improved weight gains and, overall, treated dogs survived 1.36 times longer than affected untreated dogs (P < 0.05). ACE inhibitor treatment of affected dogs significantly delayed (P < 0.05) the onset of an increase in serum creatinine concentration, tended to delay the decline of glomerular filtration rate and effective renal plasma flow (ERPF), significantly improved (P < 0.05) the ERPF at 110-154 days of age, and significantly slowed (P < 0.01) the rate of increase of proteinuria. Affected treated dogs showed a significant (P < 0.05) transient reduction in glomerular basement membrane splitting. Thus, ACE inhibitor treatment of Samoyed dogs with X-linked HN produced beneficial effects with respect to renal function, renal structure, and survival.

Angiotensin-Converting Enzyme Inhibitors↗

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

AIDS-Related Opportunistic Infections↗

Primary care and patient perceptions of access to care.

BACKGROUND: Although much is known about how insurance affects access to care, it is unclear whether good primary care contributes to access. The purpose of this study was to determine how optimal primary care given by providers at a regular place of care, defined in terms of continuity, comprehensiveness, communication, and availability, contributed to perceptions of access to care in a large population-based probability sample of adults. METHODS: Data were from a cross-sectional survey of 6674 English- and Spanish-speaking adults 18 to 64 years of age, randomly sampled from 41 urban California communities with a range of levels of access to care. RESULTS: Following adjustment for sociodemographics and need for care, we found that having "optimal" primary care contributed independently to improved self-rated access, as did having health insurance, a regular place, and a regular provider. The largest difference n access was between having any health insurance and not having insurance. Once insurance was available, each additional element contributed in a cumulative manner to self-rated access. For those with insurance and a regular place, adding optimal primary care improved self-rated access to an extent similar to adding a regular provider. CONCLUSIONS: We conclude that although providing insurance to the uninsured is the most effective means of improving self-rated access, the other elements each improve access as well. Once insurance and a regular place are provided, good primary care at that place may be equivalent to having a regular provider in terms of perceived access. Results support promotion of primary care as a model of health care that encourages good access.

Adolescent↗

Potent blood pressure raising effects of activated coagulation factor XII.

A new pressor protein (NPP) in trypsin-activated human plasma was recently reported, whose blood pressure raising effects in bioassay rats are potentiated 300% after treatment with angiotensin I converting enzyme inhibitors (captopril). Pure NPP showed good N-terminal sequence homology with coagulation factor beta FXIIa, and little of it was present in FXII-deficiency plasmas (> or = 99%, n = 4). The present experiments confirm this in four additional FXII-deficiency plasmas. Further, (i) adding highly purified coagulation FXII, alpha FXIIa, or beta FXIIa fragment restores pressor activity to such plasmas, but only after activation with trypsin. (ii) Such requirement for trypsin suggests that no factor is structurally identical with NPP to begin with but that all can be activated to NPP. (iii) When injected directly by vein, only beta FXIIa is pressor, suggesting closest structural resemblance to NPP and (or) readiest endogenous conversion to NPP. (iv) NPP and beta FXIIa are cardiotonic: they both raise systolic pressure more than the diastolic, with a concomitant increase in heart rate. These observations support NPP's structural relationship with beta FXIIa and connect coagulation and blood pressure mechanisms in a new way, whose significance to the physiology and pathophysiology of blood pressure regulation remains to be established.

Adolescent↗