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Biomedical subjects

W R Bowie

Publications and source records attributed to W R Bowie.

At least 19 recordsLinked to original sources

Management of Chlamydia trachomatis genital infections: reported practices of primary care physicians.

OBJECTIVE: To determine the knowledge of primary care physicians about Chlamydia trachomatis genital infection and its management. DESIGN: Self-administered questionnaire comprising direct questions and hypothetical cases. PARTICIPANTS: All 108 general and family practitioners on the north shore of Vancouver were sent the questionnaire; 79 (73%) responded. RESULTS: There was a reasonable level of knowledge in many areas, particularly among the physicians who had graduated more recently than the others. Virtually all stated that they have access to chlamydial diagnostic testing, and most indicated that they test for chlamydial infection at least occasionally. However, many of the respondents failed to consider that youths in their practice may be sexually active, and only 28% knew that women 15 to 19 years of age have the highest reported rates of chlamydial infection. Many of the physicians were confused about syndromes that are or are not associated with C. trachomatis infection; this indicated the possibility of inappropriate testing and treatment decisions. If they had to test for C. trachomatis in a prepubescent girl 34% reported that they would obtain a specimen from the endocervix, a technique that is inappropriately invasive. When presented with a positive test result many of the respondents failed to consider the possibility of a false-positive result. Fortunately all of the physicians were well informed about correct treatment regimens for C. trachomatis infection, although many did not realize how effective they really are. In the case of a young man with suspected or proven gonorrhea or a young female outpatient with pelvic inflammatory disease, only 19% and 20% respectively stated that they would prescribe a regimen appropriate for both penicillinase-producing Neisseria gonorrhoeae and C. trachomatis. Many of the respondents had not heard of management guidelines, and fewer still reported that they consult them. CONCLUSIONS: Despite the availability of several sets of guidelines there appear to be important gaps in the knowledge and practice of many primary care physicians with respect to genital infections. Since the preparation of guidelines is time-consuming and expensive, further work should be done to evaluate their impact and to address their limitations.

Adolescent

Human papillomavirus infection of the uterine cervix. Tissue sampling and laboratory methods affect correlations between infection rates and dysplasia.

Two common tissue sampling techniques--colposcopic biopsy and cervical scrape--and two common human papillomavirus (HPV) detection techniques--Southern blot and dot blot (SB and ViraPap [VP])--were compared to determine whether differences in these techniques alter correlations between "oncogenic" HPVs and cervical neoplasia. In 87 women with persistently abnormal Papanicolaou (Pap) smears, concurrent biopsy and scrape specimens contained HPV in 21 (24%) and contained no HPV in 26 (30%); 30 scrape specimens (34.5%) tested positive when the biopsy tested negative and 10 (11.5%) scrape specimens tested negative when the biopsy tested positive (overall concordance, 54%). Concordance for the most prevalent HPVs (16/18) was 59%. In carcinoma in situ, HPV was found in biopsy samples significantly more frequently than in scrape specimens: 17 of 23 (75%) biopsy samples versus 9 of 23 (39%) scrape specimens (P = 0.018). Conversely, in mild or no dysplasia, 0 of 42 biopsy samples tested positive for HPV 16/18 compared with 12 of 42 scrape specimens (29%; P = 0.0001). Of 229 specimens analyzed by SB and VP, 43 (19%) tested positive and 148 (65%) tested negative for HPV by both methods (concordance, 84%). Corroborative results indicated that 29 of 35 (83%) VP-positive SB-negative results were truly positive compared with none of three SB-positive VP-negative results. Both the cervical sampling technique and the method for HPV detection can significantly affect statistical correlations between cervical dysplasia and HPV type.

Biopsy

Comparison of an in vitro method and an in vivo method of Giardia excystation.

An in vitro method and an in vivo method of excystation were compared to determine the most useful method for the retrieval of Giardia duodenalis isolates. Cysts from 11 Giardia strains were used. In vitro excystation produced motile trophozoites in 16 sets, while in vivo excystation produced trophozoites in all of the 21 comparative sets of excystations. Few cultures were lost because of contamination by either method (17% of in vitro-derived trophozoites versus 23% of in vivo-derived trophozoites; P greater than 0.05). Both methods demonstrated comparable isolate retrieval rates (15% of in vitro-derived trophozoites adapting to culture compared with 29% of in vivo-derived trophozoites; P greater than 0.05), although analysis of the strains retrieved showed that two isolates were retrieved from in vitro excystation alone, compared with four from in vivo excystation. Analysis that included results of extra in vivo cultures showed that a total of nine isolates were retrieved by using this type of excystation. Despite the disadvantages of cost and labor, in vivo excystation appears to be more useful than in vitro excystation for isolate retrieval at the present time.

Animals

Effective treatment of urethritis. A practical guide.

Most cases of urethritis can be readily treated using recommended regimens. The most important causes of urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae, and initial treatment is directed at them. Optimal management requires obtaining a thorough sexual history, evaluation for objective clinical and laboratory evidence of infection, antimicrobial therapy directed towards the major aetiologies, and evaluation and treatment of sexual partners. Treatment of gonorrhoea requires a single-dose regimen active against N. gonorrhoeae, plus a regimen active against C. trachomatis and nongonococcal urethritis. The usually recommended treatment for N. gonorrhoeae is a single dose of ceftriaxone 250mg intramuscularly, but there are many alternatives, including oral ones. Only in very restricted geographical areas and under restricted situations are penicillins still reliable against N. gonorrhoeae. Recommended optimal treatment of C. trachomatis or nongonococcal urethritis currently requires 7 days' treatment with a tetracycline. Some guidelines now propose ofloxacin 300 mg orally twice daily for 7 days as an equivalent alternative, and there are very promising data with a single dose therapy with azithromycin, a long-acting macrolide antimicrobial. Using recommended regimens, microbiological failure is infrequent in compliant patients. Recurrent urethritis is, however, frequent. For patients who receive recommended treatment and do well, no follow-up cultures are needed. Patients with persistent or recurrent symptoms require careful re-evaluation of the patient, documentation of urethritis, and retreatment with antimicrobial agents a second time if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leucocytes in urethral secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

Microscopy-based techniques.

Microscopic evaluation of specimens for detection of STD is a key element in the diagnosis and timely management, particularly of symptomatic patients. It is rapid and inexpensive, and can be used effectively with minimal resources. When cultures are available, it should be used in conjunction with them, since culture results are not available at the time the patient is seen.

Female

High-risk STD/HIV behavior among college students.

The current sexually transmitted disease (STD) epidemic in adolescents has led to concern about the potential for spread of the human immunodeficiency virus (HIV). In 1988, a total of 5514 students in first-year community college and university classrooms across Canada were surveyed to assess STD/HIV-related knowledge, attitudes, and risk behavior. The students' mean age was 19.7 years; the male-to-female ratio was 1:1.4. Students knew more about HIV/acquired immunodeficiency syndrome than other STDs. Of the 74.3% of the men and 68.9% of the women who were coitally active, 14.3% of the men and 18.6% of the women had participated in anal intercourse and 5.5% reported a previous STD. Only 24.8% of the men and 15.6% of the women always used a condom during sexual intercourse. Among the 21.3% of the men and 8.6% of the women with 10 or more partners, regular condom use was reported in only 21% and 7.5%, respectively. In this subgroup, anal intercourse was practiced by 26.9% of the men and 34.8% of the women, and previous STD was reported by 10.6% and 24.2%, respectively. Factors associated with not using a condom included number of sexual partners, embarrassment about condom purchase, difficulty discussing condom use with a partner, use of oral contraceptives, insufficient knowledge of HIV/STDs, and the belief that condoms interfere with sexual pleasure. These factors are potentially amenable to change. Effective, behaviorally focused educational programs are needed to improve condom use and reduce STD/HIV risk.

Adolescent

Approach to men with urethritis and urologic complications of sexually transmitted diseases.

The most important causes of urethritis, and epididymitis in younger men, are C. trachomatis and N. gonorrhoeae. Management of these syndromes requires a thorough sexual history, genital examination, evaluation for objective and laboratory evidence of infection, antimicrobial therapy directed toward the major etiologies, and evaluation and treatment of sexual partners. Treatment of N. gonorrhoeae requires use of a single-dose regimen active against this organism, plus a 7- to 10-day tetracycline regime active against C. trachomatis and nongonococcal urethritis. With recommended regimens, microbiologic failure is infrequent in compliant patients. Recurrent urethritis is frequent, however. The management of patients with persistent or recurrent symptoms requires careful reevaluation of the patient, documentation of urethritis, and re-treatment with antimicrobials if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leukocytes in urethral secretions. Additional treatment beyond this point usually is not indicated, even though a proportion of men will remain symptomatic and some of these will have increased numbers of polymorphonuclear leukocytes in urethral secretions. The most important causes of prostatitis, and epididymitis in older men or men with urethral structural abnormalities, are classical urinary tract pathogens rather than sexually transmitted pathogens. Management of these infections includes documentation of the infection and treatment directed toward the specific pathogen. Men with symptoms of "prostatitis" must be evaluated using both urine and prostatic secretions to document infection and inflammation. The majority of men with such symptoms do not have an infection that can be documented. These men respond poorly to medications. Men with documented chronic bacterial prostatitis require long courses of antimicrobials to effect cure. In some cases, however, the disease is intractable, and chronic suppression with antimicrobials may be necessary.

Chlamydia Infections

Single-dose oral cefixime versus amoxicillin plus probenecid for the treatment of uncomplicated gonorrhea in men.

In this randomized study, a single 800-mg oral dose of cefixime cured 96 of 97 men with uncomplicated gonococcal urethritis, compared with 44 cures of 46 men who received standard therapy with amoxicillin (3 g) plus probenecid (1 g). Both regimens were ineffective against coexistent infection with Chlamydia trachomatis and Ureaplasma urealyticum. Cefixime was well tolerated, and all side effects were mild and self-limited.

Adolescent

The effect of Trichomonas vaginalis and the role of pH on cell culture monolayer viability.

In vitro, Trichomonas vaginalis produces contact-dependent cytotoxicity in which the monolayers are disrupted and monolayer cells die. In contrast, when cell-free filtrates of T. vaginalis culture supernatants are applied to a monolayer, detachment occurs but cell viability is maintained. Growth of T. vaginalis in culture results in a dramatic fall in pH. Both in systems where T. vaginalis grew in physical contact with McCoy cells and where they were physically separate, monolayers still disrupted; but the rate of death of McCoy cells significantly decreased when pH was rigidly controlled. This would indicate that cell death attributed to contact-dependent cytotoxicity is in part due to the drop in pH when T. vaginalis is grown in vitro.

Animals

Dose-ranging study of fleroxacin for treatment of uncomplicated Chlamydia trachomatis genital infections.

Men and women with suspected or proven genital infections caused by Chlamydia trachomatis were enrolled in a double-blind study to evaluate the efficacy and tolerability of fleroxacin. Patients received either 400, 600, or 800 mg once daily for 7 days and were monitored approximately 2, 4, and 7 weeks after initiation of therapy. In men monitored for at least 6 weeks or until failure of the therapy, fleroxacin failed to eradicate C. trachomatis in three of eight on the 400-mg regimen, in one of four on the 600-mg regimen, and in four of seven on the 800-mg regimen. All five women monitored for at least 6 weeks became culture negative. There was no association between in vitro susceptibility of C. trachomatis to fleroxacin and outcome, with MICs being 4 to 8 migrograms/ml for almost all isolates tested. Among those with positive cultures for Ureaplasma urealyticum initially, the first follow-up cultures remained positive in 8 (29%) of 28 men and 8 (50%) of 16 women. Independent of culture results, men with nongonococcal urethritis receiving 800 mg of fleroxacin were significantly more likely to show a clinical response than men receiving 400 or 600 mg (93 versus 54%). Adverse events were frequent, often severe, and dose related. Insomnia and photosensitivity reactions were the most important. The adverse reactions and unacceptably high rates of microbiologic failure resulted in premature termination of the study.

Adolescent

Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin.

New fluoroquinolones have generally been well tolerated. In a double-blind evaluation of oral fleroxacin, using 400, 600, or 800 mg once daily for 7 days in an ambulatory setting for treatment of uncomplicated genital infections, we encountered unexpectedly high rates of adverse reactions. The objective of this analysis was to determine whether any factors in addition to dose could be found to account for our observations. Adverse reactions developed in 66 (84%) of 79 individuals, and severe reactions arose in 38 (48%). Most frequent were central nervous system reactions (70%), with insomnia being especially frequent (49%); gastrointestinal reactions (39%) and photosensitivity reactions (10%) were also common. Development of any reaction (central nervous system reactions, insomnia, and severe intestinal reactions) was dose related. Development of photosensitivity reactions correlated with an outdoor occupation. No other factors, including usual daily caffeine use, correlated with the development of adverse reactions. In our study, fleroxacin taken as a single daily 600- or 800-mg dose was associated with an unacceptably high rate of adverse reactions. Other studies are required to determine whether this problem is unique to fleroxacin or will occur with higher doses of other fluoroquinolones possessing similar chemical modifications and/or good tissue penetration and very long half-lives.

Adolescent

Isolation of a cell-detaching factor of Trichomonas vaginalis.

The pathogenetic role of soluble products of Trichomonas vaginalis growth in culture is controversial. To evaluate this role, T. vaginalis was grown in broth and cell culture and the cell-free filtrate was applied to fresh cell culture monolayers. When adjusted to pH 6.5, filtrates obtained from 22-h culture growth totally disrupted McCoy, HEp-2, human foreskin fibroblast, and Chinese hamster ovary cell monolayers within 6 h. These detached cells remained greater than 90% viable. This cell-detaching factor (CDF) was heat and acid labile, with a pH optimum of 6.5. CDF has trypsinlike activity which disrupts monolayer cells, but cells do not die if the pH is controlled. CDF was purified by ethanol precipitation, ammonium sulfate fractionation, and ion-exchange and gel filtration column chromatography. A 200,000-molecular-weight glycoprotein which was also immunogenic by immunoblot with human sera reactive to T. vaginalis was isolated in this manner. This confirms the presence of a specific soluble CDF derived from T. vaginalis whose application may be important as a diagnostic tool and in further studies of pathogenesis.

Ammonium Sulfate

Isoenzyme analysis of human and animal isolates of Giardia duodenalis from British Columbia, Canada.

Isoenzyme patterns of 32 isolates of Giardia duodenalis, obtained from 6 beavers and 11 humans from British Columbia, plus 15 other isolates were evaluated using thin-layer starch-gel electrophoresis. We attempted to use 12 enzymes; 9 gave reproducible and interpretable results. The isoenzyme patterns of the isolates were classified into 12 groups with 17 (53%) of the 32 isolates confined to 1 group. The other 11 groups each comprised only 1 or 2 isolates. There was no obvious correlation between clinical symptoms and isoenzyme patterns. Our findings suggest that beavers, like humans and gerbils are receptive to organisms with many different isoenzyme patterns.

Animals

Giardia duodenalis: enhanced growth in cell culture.

Growth of Giardia duodenalis in broth and in animals has been studied in considerable detail. In contrast, the kinetics of growth in cell culture have been little evaluated. In this study, in vitro growth of G. duodenalis was evaluated in cell culture, primarily using mouse McCoy cells in vials. The media used were Giardia broth (TYI-G), Trichomonas vaginalis broth (TYI-T), and standard cell culture media (CMGA) alone and in combination (2 parts by volume CMGA to one part of TYI broth). Addition of cell culture enhanced the sensitivity of the systems in detecting low numbers of G. duodenalis. Growth was identified consistently with inocula less than or equal to 10/ml, and often with a calculated 10-1/ml inoculum with CMGA/TYI-T and CMGA/TYI-G with cells, and with TYI-G with and without cells. The 2 preferred systems for sensitivity and growth were CMGA/TYI-G with cells and TYI-G with cells. The pH fell minimally in the growth systems and, if CMGA was in the media, cell monolayers remained intact and viable throughout the experiment. In preliminary experiments, cell cultures did not allow growth of one strain of G. muris. These cell culture systems may be useful for detection of low numbers of non-laboratory adapted trophozoites, and should be useful in evaluating the interaction of G. dudodenalis with cells in culture.

Animals