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Biomedical subjects

C A Gaydos

Publications and source records attributed to C A Gaydos.

At least 37 records · Page 2Linked to original sources
PubMed2000

Atherosclerosis in apoE knockout mice infected with multiple pathogens.

Cytomegalovirus (CMV) and Chlamydia pneumoniae (CP) possibly contribute to atherosclerosis. Murine CMV (MCMV) and CP increase lesion size in apoE knockout mice. In this study, apoE knockout mice were infected with MCMV and CP to determine whether infection with multiple pathogens increases lesion size to a greater extent than either pathogen alone and whether infection with MCMV changes serum cytokine levels in a manner that could increase lesion development. One group of mice received MCMV at 2 weeks of age, followed by 2 doses of CP at 6 and 8 weeks of age. Additional groups received only MCMV or CP. Animals were killed at 16 weeks of age to determine lesion area. Infection with MCMV alone, CP alone, and both MCMV and CP increased lesion size 84% (P<.001), 70% (P<.0001), and 45% (P<.01), respectively. The MCMV-induced increase in circulating levels of interferon-gamma may have contributed to this increase.

Animals↗
PubMed2000

Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae.

Chlamydia pneumoniae infection can exacerbate atherosclerosis in animals. To test the hypothesis that antibiotic therapy inhibits the atherogenic effects of C. pneumoniae infection, 10-week-old apolipoprotein E (ApoE) null mice were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 20 weeks of age. Infection did not affect the size of the aortic lesion, and antibiotic treatment had no effect. Another group of mice, 12-week-old ApoE mice, were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 26 weeks of age. C. pneumoniae infection increased the size of the lesion in infected mice, but azithromycin did not reduce the size of the aortic lesion in infected mice. Therefore, immediate therapy of acute infection may be necessary to prevent the proatherogenic effects of C. pneumoniae infection.

Animals↗
PubMed2000

Point-of-entry screening for C. trachomatis In female army recruits. Who derives the cost savings?

BACKGROUND: Screening women for genital Chlamydia trachomatis at entry to military service provides an opportunity to reduce costs associated with sequelae of this infection. However, financial responsibility for screening may be debated. More than 50% of recruits return to civilian life within 2 years. The military and the civilian health care systems would both benefit from a screening program. OBJECTIVE: To assess the cost-effectiveness and relative cost savings to the military and civilian health sectors of three screening strategies for U.S. Army female recruits for C. trachomatis using urine ligase chain reaction: screening all recruits, screening recruits aged < or = 25 years, and no screening. METHODS: We applied a decision analytic model. Cost factors included screening, lost military training, morbid pelvic inflammatory disease, and other sequelae. Using a 5-year analytic horizon, we conducted analyses from military and civilian perspectives. RESULTS: Screening 10,000 female army recruits would cost 193,500 dollars and prevent 282 cases of sequelae, with a projected savings of 53,325 dollars to the military and 505,053 dollars to the civilian sector. From a military perspective, screening women aged < or = 25 years provided the highest cost savings. Screening all female recruits incurred an incremental cost of $1199 per sequela prevented. From a civilian perspective, screening all recruits offered the greatest cost savings. CONCLUSIONS: Screening female Army recruits for C. trachomatis offers substantial savings in health care costs for both the military and civilian health care systems. Relative financial benefit derived from recruit screening is disproportionate; greatest cost savings are enjoyed by the civilian sector.

Adult↗
PubMed2000

Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results.

The lack of standardization in chlamydia serology has made interpretation of published data difficult. This study was initiated to determine the extent of interlaboratory variation of microimmunofluorescence (MIF) test results for the serodiagnosis of Chlamydia pneumoniae infections. Identical panels of 22 sera were sent to 14 laboratories in eight countries for the determination of IgG and IgM antibodies by MIF. Although there was extensive variation in the numeric titer values, the overall percentage agreement with the reference standard titers from the University of Washington was 80%. For results by serodiagnostic category, the best agreement was for four-fold rise in IgG titers, while the lowest agreement was for negative or low IgG titers. Agreement for IgM titers was 50%-95%. Four laboratories failed to discern false-positive IgM titers possibly because of the presence of rheumatoid factor. Further studies are underway to determine the source of interlaboratory variation for the MIF test.

Antibodies, Bacterial↗
PubMed2000

Polymerase chain reaction detection of Chlamydia pneumoniae in circulating white blood cells.

Several recently published studies suggest that Chlamydia pneumoniae may represent a risk factor for atherosclerosis or its complications. In order to establish whether C. pneumoniae is causally linked to atherosclerotic diseases, clinical intervention trials may be needed. However, to identify eligible subjects with a persistent C. pneumoniae infection and to monitor the effect of antibiotic therapy, there is a need for a reliable diagnostic marker. Blood-based polymerase chain reaction assays may be of value for identifying patients persistently infected with C. pneumoniae and for assessing the microbiologic efficacy of antichlamydial therapy in clinical intervention trials.

Animals↗
PubMed2000

Growth in vascular cells and cytokine production by Chlamydia pneumoniae.

The proposed pathogenesis of Chlamydia pneumoniae in atherosclerosis is supported by the finding that C. pneumoniae can initiate and sustain growth in human vascular cells. In vitro growth of C. pneumoniae is found in macrophages, peripheral blood monocyte (PBMC)-derived macrophages, endothelial cells, and aortic artery smooth muscle cells. U-937 macrophages infected with C. pneumoniae are capable of transmitting the infection to human coronary artery endothelial cells (CAEC) with direct cellular contact. Production of cytokines by cells infected with C. pneumoniae indicates that the organism can stimulate the immune system. CAEC infected with C. pneumoniae produce more interleukin-8 than cells sham inoculated with negative control cells. When interferon-gamma is used to stimulate HEp-2 cells, U-937 cells, and PBMC (before infection with C. pneumoniae), inhibition of a productive growth cycle occurs in a dose-related response. Studies are needed to learn the relationship between productive infection and persistence, the ability of C. pneumoniae to affect the immune response, and the potential for C. pneumoniae to influence atheromatous lesions.

Blood Vessels↗
PubMed2000

Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae.

The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for their ability to detect Neisseria gonorrhoeae infections. Test performance compared to that of culturing was evaluated for 2,192 matched endocervical swab and urine specimens obtained from women and for 1, 981 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a confirmatory PCR test for an alternative target sequence within the N. gonorrhoeae 16S rRNA gene were considered to be true positives. The overall prevalences of gonorrhea were 6.6% in women and 20.1% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.8% of the specimens and exhibited virtually identical sensitivities and specificities. The results that follow are for the COBAS AMPLICOR format. With the infected patient as the reference standard, the resolved sensitivities of PCR were 92.4% for endocervical swab specimens and 64.8% for female urine specimens. There were no significant differences in these rates between women with and without symptoms. Among symptomatic men, COBAS AMPLICOR sensitivities were 94.1% for urine and 98.1% for urethral swabs; for asymptomatic men, the results were 42.3 and 73.1%, respectively. In comparison, the sensitivities of culturing were 84.8% for endocervical specimens, 92.7% for symptomatic male urethral specimens, and only 46.2% for urethral specimens obtained from asymptomatic men. When PCR results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.5% for endocervical swab specimens, 99.8% for female urine specimens, 98.9% for male urethral swab specimens, and 99.9% for male urine specimens. The internal control revealed that 2.1% of specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 99.2% of specimens because 60.0% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR CT/NG test for N. gonorrhoeae exhibited high sensitivity and specificity with urethral swab and urine specimens from men and endocervical swab specimens from women and thus is well suited for diagnosing and screening for N. gonorrhoeae infection.

Animals↗
PubMed2000

Touchdown enzyme time release-PCR for detection and identification of Chlamydia trachomatis, C. pneumoniae, and C. psittaci using the 16S and 16S-23S spacer rRNA genes.

Three touchdown enzyme time release (TETR)-PCR assays were used to amplify different DNA sequences in the variable regions of the 16S and 16S-23S spacer rRNA genes specific for Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci as improved tests for sensitive diagnosis and rapid species differentiation. The TETR-PCR protocol used 60 cycles of amplification, which provided improved analytical sensitivity (0.004 to 0.063 inclusion-forming unit of Chlamydia species per PCR). The sensitivity of TETR-PCR with primer set CTR 70-CTR 71 was 96.7%, and the specificity was 99.6%, compared to those of the AMPLICOR PCR for the detection of C. trachomatis in vaginal swab samples. TETR-PCR for C. pneumoniae with primer set CPN 90-CPN 91 was 90% sensitive and 93.3% specific compared with a nested PCR with primer set CP1/2-CPC/D for clinical respiratory samples. TETR-PCR for C. psittaci with primer set CPS 100-CPS 101 showed substantial agreement with cell culturing (kappa, 0.78) for animal tissue samples. Primer sets were then combined into a single multiplex TETR-PCR test. The respective 315-, 195-, and 111-bp DNA target products were precisely amplified when DNA from each of the respective Chlamydia species or combinations of them was used. Multiplex chlamydia TETR-PCR correctly identified one strain of each of the 15 serovars of C. trachomatis, 22 isolates of C. pneumoniae, and 20 isolates of C. psittaci. The primer sets were specific for each species. No target products were amplified when DNA from C. pecorum or a variety of other microorganisms was tested for specificity. TETR-PCR with primers selected for specific sequences in the 16S and 16S-23S spacer rRNA genes is a valuable test that could be used either with individual primers or in a multiplex assay for the identification and differentiation of Chlamydia species from culture isolates or for the detection of chlamydiae in clinical samples.

Base Sequence↗
PubMed2000

Multicenter evaluation of the AMPLICOR and automated COBAS AMPLICOR CT/NG tests for detection of Chlamydia trachomatis.

The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for the ability to detect Chlamydia trachomatis infections. Test performance compared to that of culture was evaluated for 2,236 matched endocervical swab and urine specimens obtained from women and for 1,940 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a direct fluorescent-antibody test or in a confirmatory PCR test for an alternative target sequence were resolved as true positives. The overall prevalences of chlamydia were 2.4% in women and 7.2% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.1% of the specimens. With the infected patient as the reference standard, the resolved sensitivities of COBAS AMPLICOR were 89.7% for endocervical swab specimens, 89.2% for female urine specimens, 88.6% for male urethral swab specimens, and 90.3% for male urine specimens. When results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.4% for endocervical swab specimens, 99.0% for female urine specimens, 98.7% for male urethral swab specimens, and 98.4% for male urine specimens. The internal control revealed that 2.4% of the specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 98.6% of the specimens because 59.1% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR and AMPLICOR CT/NG tests for C. trachomatis exhibited equally high sensitivity and specificity with both urogenital swab and urine specimens and thus are well suited for screening for C. trachomatis infection.

Automation↗
PubMed2000

The cost-effectiveness of varicella screening and vaccination in U.S. Army recruits.

Varicella outbreaks in the U.S. Army disrupt training, reduce readiness, and represent substantial costs. Vaccination of susceptible individuals may be cost-effective. We conducted a cost-effectiveness analysis comparing screening of all incoming recruits and vaccination of susceptible individuals at either initial entry training (IET) or medical entrance processing station (MEPS), universal vaccination at IET, and no intervention. Primary health outcomes included the number of varicella cases prevented during the 8-week initial training period. The varicella hospitalization rate was 21.6 per 10,000 per year. In 100,000 recruits, 36 cases of varicella are expected at a cost of $181,000 in the absence of an intervention. Screening at IET would prevent 4 cases but would cost an additional $3,255,000 more than no intervention. Screening at MEPS would prevent 3 cases and save $521,000 per case prevented during the IET but would cost $2,734,000 more than no intervention. Universal vaccination would prevent 2 cases but would cost $15,858,000 more than MEPS screening and $18,592,000 more than no intervention. These results are robust. Cost per case of varicella prevented ranged from $390,000 to $7.9 million. Scarce prevention resources could be more cost-effectively allocated to other prevention programs.

Absenteeism↗
PubMed1999

Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.

BACKGROUND: The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities. METHODS: This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios. FINDINGS: The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses. INTERPRETATION: We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.

Acquired Immunodeficiency Syndrome↗
PubMed1999

In vitro infection and pathogenesis of Chlamydia pneumoniae in endovascular cells.

The strength of the epidemiologic and clinical associations of Chlamydia pneumoniae with atherosclerosis can be increased by the demonstration that C pneumoniae can initiate and sustain growth in human vascular cells as well as in animal models. To investigate the biological basis for the dissemination and proliferation of this organism in vascular cells, the in vitro growth of C pneumoniae was studied in 2 macrophage cell lines, peripheral blood monocyte (PBMC)-derived macrophages, human bronchoalveolar lavage (BAL) macrophages, several endothelial cell lines, and aortic artery smooth muscle cells. Five of 5 strains of C pneumoniae were capable of 3 passages in human U-937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage as compared with growth in HEp-2 cells. Both human BAL macrophages and PBMC-derived macrophages were able to inhibit C pneumonia eafter 96 hours' 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. C pneumoniae was also capable of growing in endothelial cells derived from human cadaver coronary artery endothelial cells (CAEC). U-937 human macrophages that were infected with C pneumoniae were capable of transmitting the infection to CAEC when they were brought into contact with the endothelial cells by centrifugation, rocking overnight, and direct layering overnight, with and without using artificial laboratory tissue culture enhancements, such as centrifugation of the inoculum and cycloheximide in the growth media. 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, which when followed by an immune response may contribute to atheroma formation in vivo. Stimulation of cytokine responses by infection with C pneumoniae has indicated that this organism is capable of interacting with the immune system. In vitro infection by C pneumoniae of U-937 macrophages stimulated the production of IL-1beta, IFN-gamma, and TNF-alpha in tissue culture. Human CAEC that are infected with C pneumoniae produce more IL-8 compared with those inoculated with killed C pneumoniae or negative control cells, indicating a chemokine response to infection that may play a role in recruitment of inflammatory cells to sites of infection in vascular cells. When IFN-gamma was used to up regulate HEp-2 and U-937 cells before infection by C pneumoniae, inhibition of a lytic growth cycle occurred in a dose related response. However, removal of the IFN-gamma after 24 to 48 hours' exposure allowed subsequent productive growth in the cells, perhaps indicating the prior induction of a persistent infection. More studies are needed to study the complex relationship between lytic infection and persistence, the ability of C pneumoniae to affect the immune response of vascular cells, and the potential for C pneumoniae to influence the initiation of or progression of atheromatous lesions.

Cell Division↗
PubMed1999

Control of Chlamydia trachomatis infections in female army recruits: cost-effective screening and treatment in training cohorts to prevent pelvic inflammatory disease.

CONTEXT: Chlamydia trachomatis genitourinary infections in females can lead to serious and costly sequelae. Programs such as basic (initial entry) military training with controlled points of entry offer an opportunity to screen large cohorts of women at risk for infection. OBJECTIVE: To assess the cost-effectiveness of three interventions for C. trachomatis infections in women beginning Army training: 1) screening using urine ligase chain reaction (LCR) by age, 2) unrestricted testing using urine LCR, and 3) universal antibiotic treatment with azithromycin. DESIGN: Cost-effectiveness analysis from a military perspective. SETTING AND PATIENTS: A hypothetical cohort of 10,000 women who intended to complete at least 2 years of military service was studied. Analysis was based on data from 13,204 female trainees screened for chlamydial infection at Fort Jackson, SC. OUTCOMES: Program and training costs, cost of illness averted, and pelvic inflammatory disease (PID) prevented were determined for a 1-year follow-up period. Using sensitivity analysis, outcomes over 2 years were studied. RESULTS: At a 9.2% prevalence, no screening resulted in $220,900 in training and sequelae costs and 276 cases of PID. Screening by age produced the lowest cost $217,600, over a 1-year period and prevented 222 cases of PID for a cost-savings of $15 per case of PID prevented. Universal testing prevented an additional 11 cases of PID at a cost of $226,400, or costing $800 per additional case of PID prevented over age-targeted screening. Universal treatment prevented an additional 32 cases of PID and cost $221,100, saving $167 per additional cases of PID prevented over universal screening. Over a 2-year period, universal treatment provided the highest cost-savings and prevented the most disease. CONCLUSION: Screening by age provided a cost-savings to the Army over a 1-year period. Other organizations accessing large cohorts of young women could also benefit, even in the short term, from implementation of an age-based chlamydial screening program. Universal testing or universal treatment may be warranted in which long-term societal goals, such as maximum reduction of PID, are relevant.

Adult↗
PubMed1998

Chlamydia trachomatis infections in female military recruits.

BACKGROUND: Asymptomatic genital Chlamydia trachomatis infections in women can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To design a chlamydia-control program, we conducted a large survey of women in the U.S. military. METHODS: From January 1996 through December 1997, urine samples from 13,204 new female U.S. Army recruits from 50 states were screened by ligase chain reaction for C. trachomatis infection. Information on potential risk factors was obtained by questionnaire. With multivariate analysis, we identified criteria for a screening program. RESULTS: The overall prevalence of chlamydial infection was 9.2 percent, with a peak of 12.2 percent among the 17-year-old recruits. The prevalence was 15 percent or more among the recruits from five southern states. The following risk factors were independently associated with chlamydial infection: having ever had vaginal sex (odds ratio for infection, 5.9), being 25 years of age or less (odds ratio, 3.0), being black (odds ratio, 3.4), having had more than one sex partner in the previous 90 days (odds ratio, 1.4), having had a new partner in the previous 90 days (odds ratio, 1.3), having had a partner in the previous 90 days who did not always use condoms (odds ratio, 1.4), and having ever had a sexually transmitted disease (odds ratio, 1.2). A screening program for subjects 25 years of age or less (87.9 percent of our sample) would have identified 95.3 percent of the infected women. CONCLUSIONS: Among female military recruits, the prevalence of chlamydial infection is high. A control program that screens female recruits who are 25 years old or younger with urine DNA-amplification assays has the potential to reduce infection, transmission, and the sequelae of chlamydial infection.

Adolescent↗