Determination of biogenic amines using heterocyclic cation and aromatic anion elution.
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Biomedical subjects
Publications and source records attributed to K K Holmes.
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In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.
A prospective study of 37 men and 32 women with culture-proved genital herpes simplex virus (HSV) infection was undertaken to characterize the clinical manifestations of the disease and effects of topical therapy with Nonoxynol 9, a nonionic surfactant active in vitro against HSV. The duration of pain, lesions, and virus shedding was significantly longer in initial than in recurrent genital HSV infection. Cervical HSV shedding occurred in 11 of 13 initial infections versus two of 19 recurrences (p less than 0.001). Type 1 HSV caused seven of 29 initial and none of 40 recurrent infections (p less than 0.01). Clinical recurrences within six weeks were detected more often in men than in women and were unrelated to the menstrual cycle. The influence of coitus on recurrence is unclear. Papanicolaou smears were transiently abnormal (Class II) in four (12.5 per cent) of 32 female patients. Evidence of herpesvirus was detected cytologic smears from only 28 (41 per cent) of 69 culture-proved external lesions and three (23 per cent) of 13 culture-positive cervices. Serology was also of limited diagnostic value except in testing paired sera from initial infections. The topical therapy had no beneficial effect.
There were 50 patients with acute epididymitis who were evaluated prospectively by history, examination and microbiologic studies, including cultures for aerobes, anaerobes, Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum. Escherichia coli was the predominant pathogen isolated from the urine of men more than 35 years old, while Chlamydia trachomatis and Neisseria gonorrhoeae were the predominant pathogens isolated from the urethra of men less than 35 years old. The etiologic role of Escherichia coli and Chlamydia trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine or urethral cultures for these agents. Chlamydia trachomatis epididymitis accounted for two-thirds of idiopathic epididymitis in young men and often was associated with oligospermia. Of 9 female sexual partners of men with Chlamydia trachomatis infection 6 had antibody to Chlamydia trachomatis, of whom 2 had positive cervical cultures for this organism and 2 others had non-gonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with Chlamydia trachomatis epididymitis and should be offered to the female sex partners.
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Vaginal washings from women attending a veneral disease clinic were examined for the presence of protease that cleaved IgA subclass 1 (IgA1). In a crude assay, vaginal washings cleaved [125I]IgA1 in 19 of 25 specimens from individuals from whom Neisseria gonorrhoeae were cultivated. Forty-six specimens from 104 women whose cultures were negative for N. gonorrhoeae also cleaved [125I]IgA1. Vaginal washings from six of six women with culture-proven gonorrhea cleaved [125I]IgA1 into low-molecular-weight components identical to those produced by partially purified IgA1-specific protease from gonococci. The hydrolysis of [125I]IgA1 by vaginal washings from women whose cultures were negative for N. gonorrhoeae yielded cleavage products that resembled those of trypsin or alpha-chymotrypsin. These findings indicate that gonococci residing in the female genital tract produce IgA1-specific protease that can be detected in the vaginal washings of infected women.
To assess the efficacy of oral erythromycin in the treatment of nonspecific vaginitis (NSV), conducted a nonrandom, unblinded pilot study among 17 women with symptoms and signs of NSV. At the completion of treatment, 10 of 13 patients had persistent symptoms, 9 of 13 had persistent abnormal discharge, and 11 of 13 had persistently positive cultures for Haemophilus vaginalis. Ten patients with persistent or relapsing NSV and four who did not complete erythromycin treatment were retreated with oral metronidazole, and 14 of 14 showed clinical improvement and eradication of H. vaginalis. The susceptibility of 27 clinical isolates of H. vaginalis to erythromycin was determined at pH 5.5, 6.0, 6.5, and 7.0. The minimal inhibitory concentration of erythromycin for H. vaginalis was approximately 10-fold higher at pH 5.5 than at pH 7.0. Erythromycin is not effective for the treatment of H. vaginalis-associated NSV; this may be partly attributable to the reduced activity of this drug in acidic vaginal secretions.
We examined the vaginal washings from patients with nonspecific vaginitis (NSV) to seek biochemical markers and possible explanations for the signs and symptoms of this syndrome. Seven amines were identified including methylamine, isobutylamine, putrescine, cadaverine, histamine, tyramine, and phenethylamine. These amines may contribute to the symptoms of NSV and may contribute to the elevated pH of the vaginal discharge. They may also be partly responsible for the "fishy" odor that is characteristic of vaginal discharges from these patients. Among the seven amines, putrescine and cadaverine were the most abundant and were present in all vaginal discharges from each of ten patients before treatment. These amines are produced in vitro during growth of mixed vaginal bacteria in chemically defined medium, presumably by decarboxylation of the corresponding amino acids. We hypothesize the anaerobic vaginal organisms, previously shown to be quantitatively increased in NSV, are responsible for the amine production, because metronidazole inhibited the production of amines by vaginal bacteria in vitro, and Haemophilus vaginalis did not produce amines. H. vaginalis did release high concentrations of pyruvic acid and of amino acids during growth in peptone-starch-dextrose medium, whereas, other vaginal flora consumed both pyruvic acid and amino acids in the same medium during growth. These findings suggest that a symbiotic relationship may exist between H. vaginalis and other vaginal flora in patients with NSV.
Fifty patients with acute epididymitis were evaluated prospectively by history, examination, and microbiologic studies, including cultures for aerobes, anaerobes, N. gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum. E. Coli was the predominant pathogen isolated from the urine of men over 35 years old and C. trachomatis and N. gonnorrheae were the predominant pathogens isolated from the urethra of men under 35. The etiologic role of E. Coli and C. trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine of urethral cultures for these agents. C. trachomatis epididymitis accounted for two thirds of "idiopathic epididymitis" in men, and was often associated with oligozoospermia. Of nine female sexual partners of men with C. trachomatis infection, six had antibody to C. trachomatis, of whom two had positive cervical cultures for this organism, and the others had nongonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with C. trachomatis epididymitis, and should be offered to their female sex partner.
Group A beta-hemolytic streptococci were isolated from 49 (10.4%) of 472 patients with pharyngitis. Throat culture results, interpreted by five observers of varying experience, showed the mean sensitivity, specificity, and predictive value of a positive Gram-stained smear of pharyngeal secretions as 73%, 96%, and 71%. Assignment to a high-risk group by clinical algorithm gave sensitivity, specificity, and predictive value of only 45%, 83%, and 23%. The Gram-stained smear is the most accurate method of early diagnosis of streptococcal pharyngitis.
We studied the relations between the cellular immune response, pre-existing complement-fixing antibody and virus type with duration of virus excretion in genital herpes simplex virus (HSV) infection. Thirty-six patients (seven with HSV-1 and 29 with HSV-2) with genital herpes underwent serologic testing, sequential viral cultures and weekly determination of lymphocyte-transformation stimulation index with inactivated HSV antic n. The duration of virus excretion was shortest in those with pre-existing complement-fixing antibody, was unrelated to virus type, and was inversely correlated with the magnitude of the mean peak stimulation index (r = -0.69, P less than 0.001). Prolonged virus excretion occurred in patients with a delayed and diminished peak index. Recurrent episodes had a higher peak index (29.4 compared to 14.5) (P less than 0.02), an earlier development of the peak during recurrences (9.1 vs. 25.8 days) (P less than 0.01) and a briefer duration of viral shedding than initial episodes. Thus, the temporal course and magnitude of the stimulation index correlate with and may determine the duration of genital HSV infection.
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To assess the cause of nonspecific vaginitis, we performed a prospective case-control study of vaginal flora and a randomized unblinded trial of different therapies. Haemophilus vaginalis was isolated from 17 to 18 women with signs of vaginitis but only one of 18 normal matched controls (P less than 0.002). The concentration of anaerobic bacteria in vaginal washings also was increased in patients. Clinical improvement and eradication of H. vaginalis occurred in one of seven patients given sulfonamide vaginal cream, two of 15 given oral doxycycline, nine of 27 given oral ampicillin, and 80 of 81 given oral metronidazole. On the seventh day of therapy signs of nonspecific vaginitis persisted in 31 of 31 with, and in two of 92 without, persistent H. vaginalis infection (P less than 0.001). These data suggest the causal role of H. vaginalis in nonspecific vaginitis, possibly in concert with vaginal anaerobes. The widespread use of sulfonamide creams is inappropriate. Metronidazole is effective, but its efficacy must be weighed against its possible toxicity.
To assess the etiologic role of C. trachomatis and other micro-organisms in "idiopathic" epididymitis, 23 men underwent microbiologic studies, including cultures of epididymal aspirates in 16. Eleven of 13 men under the age of 35 years had C. trachomatis infection whereas eight of 10 over 35 had coliform urinary-tract infection. Cultures of epididymal aspirates yielded C. trachomatis alone in five of six men under 35, and coliform bacteria alone in five of 10 over 35. These results suggest that C. trachomatis is the major cause of "idiopathic" epididymitis, and coliform bacteria the major cause of epididymitis in older men. Expressible urethral discharge and inguinal pain were more common in the chlamydial cases, whereas concurrent genitourinary abnormality and scrotal edema and erythema occurred more commonly in the coliform cases. The morbidity attributable to C. trachomatis is as serious as that attributable to Neisseria gonorrhoeae.
We have briefly presented practical approaches to the management of the most common disorders caused by sexually transmitted pathogens, including pelvic inflammatory disease, urethritis in men, genital lesions, vaginal discharge, and syphilis. Guidelines for the management of gonorrhea may change if penicillin-resistant strains become more prevalent. Areas which require further research include the treatment of genital herpes and the prevention of recurrences, the treatment of nonspecific vaginitis, and definition of the importance of metronidazole toxicity.
The antibody response to the capsular polysaccharide of Bacteroides fragilis subspecies fragilis in women with acute pelvic inflammatory disease was quantitated using a sensitive radioactive antigen-binding assay. Antibody detected by this technique correlated highly with antibody measured by quantitative precipitin analysis (r = 0.99). Paired acute- and convalescent-phase sera obtained from women from whom B. fragilis subspecies fragilis was isolated by culdocentesis showed significantly greater changes in antibody concentration than corresponding sera obtained from women with gonococcal or nongonococcal pelvic inflammatory disease when B. fragilis subspecies fragilis was not isolated from the cul-de-sac. These data indicate that the steady state of immunity to this capsular antigen is perturbed in patients with acute nongonococcal pelvic inflammatory disease from whom this organism can be cultured. This finding may indicate that B. fragilis can play a significant role in acute pelvic inflammatory disease and can be involved early in the infectious process.
Reliable data on the risk of transmission of N. gonorrhoeae would enhance our understanding of the importance of host defenses against gonorrhea and would aid in the evaluation of prophylactic measures. This paper examines the risk of transmission of gonorrhea from infected female to male and the role that variables such as race, prophylaxis and amount of exposure play in the development of gonococcal urethritis. Volunteer crew members of a large naval vessel were followed prospectively as a cohort to study their risk of acquiring gonococcal infection during a four-day liberty period in the Far East. At the same time the prevalence of N. gonorrhoeae was determined in a population of females to whom the sailors were exposed. The calculated risk of transmission per exposure with an infected partner was .19 for whites and .53 for blacks. A statistically significant relationship was noted between the risk of transmission of gonorrhea and both the number of partners and the frequency of sexual intercourse. Further, the increasing infection rate with increasing numbers of exposures in men who had a single sex partner suggests that the majority of men are in fact susceptible to gonorrhea if the quantity of exposure is sufficient.
Strains of Neisseria gonorrhoeae isolated from disseminated gonococcal infections have enhanced ability to acquire iron in an experimental host when compared with urogenital gonococcal isolates from patients with uncomplicated infections.