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T C Quinn

Publications and source records attributed to T C Quinn.

At least 19 recordsLinked to original sources

The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia.

Following infection of the host with a virus, the delicate balance between virus replication/spread and the immune response to the virus determines the outcome of infection, i.e., persistence versus elimination of the virus. It is unclear, however, what relative roles immunologic and virologic factors play during primary viral infection in determining the subsequent clinical outcome. By studying a cohort of subjects with primary HIV infection, it has been demonstrated that qualitative differences in the primary immune response to HIV, but not quantitative differences in the initial levels of viremia are associated with different clinical outcomes.

CD4 Lymphocyte Count

Myelopathy among Brazilians coinfected with human T-cell lymphotropic virus type I and HIV.

OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and HIV singly infected adults (controls) participating in a prospective HIV cohort study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist unaware of their HTLV serologic status. Patients with at least two pyramidal signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus, diminished or absent superficial reflexes, or the presence of pathologic reflexes (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy severity was quantified using the Kurtzke Functional Disability Scale (FDS); patients with FDS scores > or = 4 were considered to have significant myelopathy. Selected patients with myelopathy underwent lumbar puncture for the evaluation of intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects, 11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the association between coinfection and the presence of myelopathy remained (OR = 7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04). In addition, a higher proportion of coinfected subjects had peripheral neuropathy (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV-I was strongly associated with myelopathy among subjects infected with HIV. The relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection-associated myelopathy is not known. Coinfection may also be associated with peripheral neuropathy. Further studies are needed to elucidate the mechanisms of coinfection-associated neurologic conditions.

Adult

Epidemiologic and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships.

OBJECTIVES: To determine the frequency of Chlamydia trachomatis genital infection within sexual partnerships using highly sensitive polymerase chain reaction (PCR) amplification and to identify the variables that might modify transmission. DESIGN: Cross-sectional study of sexual partnerships comparing in vitro culture and PCR amplification for C trachomatis. SETTING: Two outpatient sexually transmitted disease clinics. PARTICIPANTS: Four hundred ninety-four people in sexual partnerships attending sexually transmitted disease clinics. MAIN OUTCOME MEASURE: Genital infection with C trachomatis. METHODS: DNA sequencing was performed to examine specific genotypes within and between partnerships. Cross-sectional analysis was performed to determine characteristics associated with concordance or discordance of infection with partnerships. RESULTS: Cultures were positive for C trachomatis in 8.5% of males and 12.9% of females (P=.03). Using PCR, more infections were identified both in males (14.2%) and in females (15.8%), and the difference in infection rates analyzed by sex was no longer significant. In 20.4% of 494 couples, at least 1 partner had PCR results positive for C trachomatis, with a concordant infection rate of 10.7%, significantly higher than the 5.5% concordant infection rate demonstrable by culture (P<.01). Male-female and female-male transmission frequencies were equal (68%). The nucleotide sequences of the major outer membrane protein gene products were identical and unique for each of 15 culture-negative, PCR-positive concordant partnerships. In concordant infections, factors associated with infection in female partners were age less than 20 years, more than 1 partner in the past 6 months, and cervical ectopy greater than 25%. CONCLUSIONS: Using PCR, the frequency of chlamydia transmission by infected males and females was nearly identical. The high rate of concordant infection, high frequency of infection among asymptomatic individuals, and high frequency of transmission regardless of sex underscore the importance of routine screening for chlamydia in both males and females, along with provision of treatment to all sexual partners of chlamydia-infected individuals.

Adolescent

Global burden of the HIV pandemic.

Within the global pandemic of HIV infection there are many different epidemics, each with its own dynamics and each influenced by many factors including time of introduction of the virus, population density, and cultural and social issues. Effective management strategies depend on knowledge of all these factors. By the year 2000, WHO projections are that 26 million persons will be infected with HIV, more than 90% of whom will be in developing countries. To control AIDS, countries must not only promote changes in individual behaviour but also address social issues such as unemployment, rapid urbanisation, migration, and the status of women.

Acquired Immunodeficiency Syndrome

Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection.

In the present study, we have determined the kinetics of constitutive expression of a panel of cytokines [interleukin (IL) 2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] in sequential peripheral blood mononuclear cell samples from nine individuals with primary human immunodeficiency virus infection. Expression of IL-2 and IL-4 was barely detected in peripheral blood mononuclear cells. However, substantial levels of IL-2 expression were found in mononuclear cells isolated from lymph node. Expression of IL-6 was detected in only three of nine patients, and IL-6 expression was observed when transition from the acute to the chronic phase had already occurred. Expression of IL-10 and TNF-alpha was consistently observed in all patients tested, and levels of both cytokines were either stable or progressively increased over time. Similar to IL-10 and TNF-alpha, IFN-gamma expression was detected in all patients; however, in five of nine patients, IFN-gamma expression peaked very early during primary infection. The early peak in IFN-gamma expression coincided with oligoclonal expansions of CD8+ T cells in five of six patients, and CD8+ T cells mostly accounted for the expression of this cytokine. These results indicate that high levels of expression of proinflammatory cytokines are associated with primary infection and that the cytokine response during this phase of infection is strongly influenced by oligoclonal expansions of CD8+ T cells.

Cells, Cultured

The laboratory evaluation of opportunistic pulmonary infections.

The patient population at risk for opportunistic pulmonary infections has increased during the last decade. The spectrum of organisms causing opportunistic infections has also grown. With an ever broader list of potential diagnosis, a specific diagnosis of the cause of pulmonary disease becomes more important. Recent microbiologic advances have helped to facilitate the laboratory diagnosis of some of these agents. Immunoassays are available for the detection of antigen in nasopharyngeal secretions (respiratory syncytial virus, influenza) in serum (Cryptococcus species), and in urine (Legionella or Histoplasma species). Rapid-culture techniques are available for the culture and detection of various viruses, including cytomegalovirus. Molecular probes can now assist in the rapid identification of Mycobacterium tuberculosis and some fungi. In the near future, polymerase chain reaction-based techniques may assist in the detection of Pneumocystis carinii and Legionella, Chlamydia, Mycoplasma, and Mycobacteria species. An expeditious evaluation of pulmonary disease requires an understanding of the differential diagnosis of likely causes of pulmonary disease in specific immunosuppressed patient populations, an understanding of the most appropriate specimens to process for these diagnoses, and an understanding of the limitations (sensitivity and specificity) of these diagnostic tests. An understanding of the most appropriate specimens and tests in a given institution should allow for early, relatively specific treatment of many potentially life-threatening infections.

Clinical Laboratory Techniques

Occupational risk of hepatitis C infections among general dentists and oral surgeons in North America.

PURPOSE: To assess the occupational risk of hepatitis C virus (HCV) infection among dental personnel. METHODS: Three hundred forty-three oral surgeons and 305 general dentists were recruited at national meetings of the American Dental Association and matched by gender, age, years of practice, and location of practice. Each participant completed a detailed questionnaire designated to measure occupational risk of blood-borne infections and supplied a sample of blood. Antibodies to HCV (anti-HCV) were assessed by second-generation enzyme immunoassay and recombinant immunoblot assay. As a marker of occupational exposure to blood-borne viruses, hepatitis B virus (HBV) surface antigen and antibodies to HBV surface and core antigens were measured by enzyme immunoassay. RESULTS: Anti-HCV was found in 2.0% of oral surgeons and 0.7% of general dentists (odds ratio [OR] = 3.2, P = 0.133). Anti-HCV was more prevalent (P < 0.01) in dental personnel who were older, had more years of practice, and had serologic markers of HBV infection. Serologic markers of HBV infection were found in 7.8% of general dentists and 21.2% of oral surgeons (OR 3.1, P < 0.001). CONCLUSIONS: These data confirm high rates of HBV infection among dental personnel, but suggest that the risk of HCV infection is considerably lower.

Adult

Feasibility of an emergency department-based, risk-targeted voluntary HIV screening program.

STUDY OBJECTIVE: To assess the feasibility and effectiveness of an emergency department-based, risk-targeted voluntary HIV screening program. METHODS: We prospectively enrolled consenting adult i.v. drug users (IDUs) not known to have HIV infection in the ED of a large inner-city hospital with a high rate of HIV infection among patients during a 10-week trial. Study patients were given confidential HIV pretest and risk-reduction counseling, with 10- to 14-day on-site ED follow-up. Follow-up included posttest counseling, reinforcement of risk-reduction practices, and a +10 incentive to cover transportation costs. HIV seropositive patients were referred to the hospital HIV clinic for further evaluation and treatment. RESULTS: Of 200 eligible IDUs, 168 (84%) consented to HIV testing. Of the 104 (62%) who returned for follow-up, 17 (16%) tested positive for HIV. Of these patients, 6 (35%) kept their initial hospital HIV clinic referral appointment, a rate consistent with the experience of the hospital HIV clinic. Of nine patients in whom CD4+ counts were performed at time of the visit, three (33%) had counts less than 200. At 3-month follow-up, 4 of 20 active IDUs (20%) had reportedly ceased drug use because of the program. The complete program costs was an estimated $16,659, $99 per enrolled patient and $521 per HIV-positive patient. CONCLUSION: An ED-based, risk-targeted HIV screening program is feasible and over time could detect a significant number of asymptomatic HIV-infected individuals, including those who should receive antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia therapy (CD4+ count less than 200). An additional benefit of ED-based HIV screening in high-prevalence EDs is the opportunity to conduct successful risk-reduction counseling in some high-risk individuals.

AIDS Serodiagnosis

Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy.

To further investigate a proposed relationship between Chlamydia pneumoniae and coronary heart disease, coronary atheromas were collected from patients undergoing percutaneous atherectomy. Fifty-eight atheroma specimens were examined by culture and polymerase chain reaction (PCR) and 22 by electron microscopy. All were negative for C. pneumoniae, except a single specimen that was PCR-positive. These results differ from studies in other populations, in which this organism was identified by nonculture methods within coronary atheromas obtained at autopsy. Anti-C. pneumoniae antibody titers from 65 of the patients were compared with those of 28 asymptomatic controls. IgG titers were higher in controls than in patients. There is no evidence that C. pneumoniae exists within atheromas in this study population, nor does seroprevalence correlate with the presence of coronary disease in these patients.

Adult

In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae.

Thirteen strains of Chlamydia pneumoniae were evaluated for their in vitro susceptibilities to azithromycin, clarithromycin, erythromycin, and tetracycline. The MIC ranges were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. The ranges for the minimal lethal concentrations were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. Clarithromycin and azithromycin were the most active antibiotics against C. pneumoniae in vitro.

Anti-Bacterial Agents

Comparison of absolute CD4+ lymphocyte counts determined by enzyme immunoassay (TRAx CD4 test kit) and flow cytometry.

Currently, CD4+ lymphocyte counts are one of the most widely used surrogate markers for monitoring disease progression in and initiating therapy for human immunodeficiency virus-infected individuals. However, the process of obtaining lymphocyte subset counts can be complex and expensive, often rendering the test inaccessible to many patients. In contrast to standard laser-based flow cytometry, the TRAx CD4 Test Kit utilizes an enzyme-linked immunoassay format to provide CD4+ lymphocyte counts by a simple and more cost-effective means. In order to evaluate the utility of the TRAx CD4+ assay in comparison with flow cytometry, heparinized blood samples were drawn from 188 infected and uninfected adult patients and 24 infected pediatric patients and evaluated by both assays. The correlation coefficient for all adult individuals tested was 0.94, and the mean absolute counts (in cells per milliliter, +/- standard deviation) were 510 +/- 358 for TRAx and 480 +/- 361 for flow cytometry. The correlation for the pediatric group was 0.93, with mean absolute counts of 956 +/- 767 for TRAx and 1,521 +/-a 1,438 for flow cytometry. Overall the TRAx CD4 Test Kit performed well in comparison to flow cytometry, and its lower cost and ease of use make it an encouraging alternative for the routine determination of CD4+ lymphocyte counts.

Adult

Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells.

Chlamydia pneumoniae has recently been associated with atherosclerotic lesions in coronary arteries. To investigate the biological basis for the dissemination and proliferation of this organism in such lesions, the in vitro growth of C. pneumoniae was studied in two macrophage cell lines, peripheral blood monocyte-derived macrophages, human bronchoalveolar lavage macrophages, several endothelial cell lines, and aortic smooth muscle cells. Five strains of C. pneumoniae were capable of three passages in human U937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage, as compared with growth titers in HEp-2 cells. Both human bronchoalveolar lavage macrophages and peripheral blood monocyte-derived macrophages were able to inhibit C. pneumoniae after 96 h of growth. Eleven C. pneumoniae strains were capable of replicating in normal human aortic artery-derived endothelial cells, umbilical vein-derived endothelial cells, and pulmonary artery endothelial cells. Infection in human aortic artery smooth muscle cells was also established for 13 strains of C. pneumoniae. The in vitro ability of C. pneumoniae to maintain infections in macrophages, endothelial cells, and aortic smooth muscle cells may provide support for the hypothesis that C. pneumoniae can infect such cells and, when infection is followed by an immune response, may contribute to atheroma formation in vivo. More studies are needed to investigate the complex relationship between lytic infection and persistence and the potential for C. pneumoniae to influence the generation of atheromatous lesions.

Cell Line

Evidence for a predominant proinflammatory conjunctival cytokine response in individuals with trachoma.

Immune responses to Chlamydia trachomatis infection in trachoma do not protect against reinfection or the development of scarring and blindness. In addition, the immunoregulatory contribution of cytokines to the development of conjunctival histopathology or protection is undefined. In this study, conjunctival cytokine mRNA transcripts were compared among subgroups of chlamydia infection status and ocular disease presentations of 50 individuals from an area where trachoma is endemic. There was a significant association of elevated interleukin (IL)-1beta, transforming growth factor beta1, and tumor necrosis factor alpha transcripts with infection, follicular inflammation, and scarring. Both gamma interferon (IFN-gamma) and IL-2 transcripts were significantly associated with infection; slightly elevated IL-2 levels were found in inflammatory disease. High IFN-gamma transcript levels were present with follicles and inflammatory disease and to a lesser extent with inflammatory scarring. The role of IFN-gamma in protection from infection or disease was not apparent from this study, since transcripts were frequently present in both chlamydial infection and disease. IL-12 (p40) transcripts were elevated in adults and children in association with follicular inflammation but not with scarring. IL-4, IL-5, and IL-10 transcripts were not detected in any samples. In conclusion, C. trachomatis infection stimulates local cytokines which favor a strong cell-mediated and proinflammatory response in both the early and later manifestations of trachoma. In addition, cytokine transcript levels that were associated with disease but no infection were characteristically lower overall than when chlamydia was present.

Adult

Evaluation of Chiron HIV-1/HIV-2 recombinant immunoblot assay.

In a study to determine the reliability, sensitivity, and specificity of the Chiron RIBA HIV-1/HIV-2 Strip Immunoblot Assay (RIBA HIV-1/2 SIA) for confirmation of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies, 1,263 serum samples from various populations in the United States, Caribbean, Africa, India, and Thailand were evaluated by RIBA HIV-1/2 SIA, and the results were compared with those obtained by an HIV-1 Western blot (immunoblot) assay. All sera were tested by HIV enzyme immunoassay, RIBA HIV-1/2 SIA, and Western blotting. Samples with discrepant results were further tested by an HIV-1 and/or HIV-2 immunofluorescent-antibody assay and HIV-1 p24 antigen assay. The RIBA HIV-1/2 SIA detected all 17 HIV-1 and HIV-2 dually reactive serum samples, all 215 HIV-2-positive serum samples, and 480 of 481 HIV-1-positive serum samples for a sensitivity of 99.8%. Of 548 negative samples, 523 were RIBA HIV-1/2 SIA negative, for a specificity of 95.4%, with 22 (4%) samples interpreted as indeterminate and 3 (0.6%) interpreted as falsely positive. Western blotting detected 391 of 548 negative samples (specificity, 71.4%), with 152 (27.7%) samples interpreted as indeterminate and 5 (0.9%) interpreted as falsely positive. In conclusion, the RIBA HIV-1/2 SIA had a sensitivity comparable to that of Western blotting and could discriminate HIV-1 from HIV-2 in one blot, providing a cost advantage. Because of its high degree of specificity, the RIBA HIV-1/2 SIA further reduced the number of indeterminate results found by Western blotting, providing a more accurate means of assessing seronegative individuals.

AIDS Serodiagnosis

Diagnosis by AMPLICOR PCR of Chlamydia trachomatis infection in urine samples from women and men attending sexually transmitted disease clinics.

Screening of urine specimens from men for Chlamydia trachomatis infection by a commercial PCR assay (AMPLICOR C. trachomatis Test; Roche Diagnostic Systems, Inc., Branchburg, N.J.) is a sensitive and specific noninvasive diagnostic assay. Since screening of women for C. trachomatis infection with the AMPLICOR C. trachomatis Test has been limited to use with endocervical swab specimens, we conducted an evaluation of the AMPLICOR C. trachomatis Test for the detection of C. trachomatis using female urine samples and compared the results of those obtained by in vitro culture and PCR of endocervical swab specimens. For 713 men we compared the performance of AMPLICOR C. trachomatis Test with urine specimens with that of culture of urethral specimens. For specimens that were PCR positive and culture negative, two additional tests were used to resolve the discrepancies: direct fluorescent-antibody assay (DFA) of sediment from a spun endocervical specimen culture vial and major outer membrane protein-based PCR of the sediment from the endocervical specimen culture vial. Of 525 urine specimens from females, 67 (12.8%) were PCR positive, and 41 (7.8%) endocervical specimens from the 525 women were culture positive. After resolution of the discrepancies, the resolved sensitivity of the urine PCR was 93.3%, whereas the sensitivity of endocervical swab specimen culture was 67.3%. Of 468 female endocervical swab specimens, 47 (10.0%) had a positive PCR result and 33 (7.0%) were culture positive. The resolved sensitivity of the endocervical swab specimen PCR was 86%. Of 415 matched female urine and endocervical swab specimens, there were 49 confirmed infections; 30 (61.2%) specimens were positive by culture of the endocervical swab specimen, 40 (81.6%) were positive by confirmed endocervical swab specimen PCR, 43 (87.8%) were positive by confirmed urine PCR, and all 49 (100%) were positive by either endocervical swab specimen PCR or urine PCR. For men, the resolved sensitivity of the urine PCR was 88%, and the sensitivity of culture was only 50.7%. These results indicate that urine PCR is highly sensitive for the detection of C. trachomatis in both women and men and provides a noninvasive technique for routine screening for chlamydial infection.

Ambulatory Care Facilities

Clinical characterization of a competitive PCR assay for quantitative testing of hepatitis C virus.

Rational clinical application of quantitative assessments of hepatitis C virus (HCV) RNA depends on an understanding of factors affecting the assay and its intrinsic variability. The effects of three types of blood collection tubes, two storage temperatures, five processing times, and two laboratories on a commercially available quantitative reverse transcriptase PCR assay (AMPLICOR HCV MONITOR) were evaluated. HCV RNA concentrations were assessed in 356 specimens representing 178 aliquots from nine patients. In a multivariate generalized linear model, HCV RNA concentrations decreased when centrifugation was delayed more than 6 h (P = 0.005) and were marginally different between laboratories (P = 0.06), but precentrifugation storage temperature (P = 1.00) and anticoagulation (P = 0.22) had no effect. After adjusting for other factors, the HCV concentration of 95% of a subject's samples were within 0.44 log. Specimens procured for reverse transcriptase PCR-based quantitative HCV testing should be centrifuged within 6 h of collection. Serial assessments should ideally be performed in the same laboratory, and changes in HCV RNA concentration of less than 0.44 log may not be biologically important.

Adult