Studies on gonococcus infection. I. Pili and zones of adhesion: their relation to gonococcal growth patterns.

The four colony types of several different strains of gonococci were isolated by selective transfers on agar. These colony variants differed in the degree of autoagglutination which occurred when they were grown in fluid medium. It was found that this clumping behavior was related to the colonial type, with type 2 isolates exhibiting the greatest autoagglutination followed by types 3, 1, and 4. Electron microscopic examination of thin sections indicated that the clumping in fluid medium was mediated by peculiar zones of adherence of the outer membranes of gonococci. These resembled the gap junctions seen in animal cell systems but differed in that the gonococcal membranes involved in the zone of adherence did not bear typical surface modifications. Electron microscopic study of negatively stained specimens of gonococci revealed that pili with a diameter of approximately 85 A and a length up to 4 micro were present on the surfaces of all type 1 and type 2 gonococci examined, and were not seen on any type 3 or 4 gonococci. The consistent presence of pili on type 1 and type 2 gonococci which are virulent colony forms and the lack of pili on avirulent colony types 3 and 4 suggests a relationship between the gonococcal pili and pathogenetic potential of the organisms.

Acquired and natural immunity to gonococcal infection in chimpanzees.

Despite the fact that gonorrhea is our most common reportable infectious disease, little is known about natural and acquired resistance to Neisseria gonorrhoeae. With the chimpanzee model, which mimics human gonococcal infection in signs, symptoms, and host response, a natural resistance to gonococcal challenge was found. One aspect of this natural resistance became evident when the cervix and oral pharynx resisted more gonococci than the urethra. Natural resistance was also shown when environmental factors were found to influence resistance to gonococcal pharyngitis. In addition to natural resistance a postinfection-acquired immunity to the gonococcus was demonstrated. Following gonococcal pharyngitis, this anatomical location successfully resisted more gonococci than were initially resisted. Similarly, more gonococci were successfully resisted in rechallenging the urethra. These findings are related to the clinic situation and suggest possible new approaches to gonorrhea control.

Quantitative determination of antibody to gonococcal pili. Changes in antibody levels with gonococcal infection.

Gonococcal pili, pure by the criteria of electron microscopic examination and polyacrylamide gel electrophoresis in sodium dodecyl sulfate, have been prepared by repeated cycles of precipitation with 0.1 M MgCl(2), followed by dissolution in 0.01 M Tris pH 8, 0.01 M NaN(3). Using a fluorescein-conjugated antibody prepared to pili from a single strain, pilar antigen(s) was found to be present in each of 18 strains of gonococci tested, and absent from strains of pilated meningococci, nonpathogenic Neisseria sp., and Escherichia coli. Purified pili, labeled with (125)I were used in an antigen binding assay to quantitatively measure antibody to pili in rabbit sera and in 561 human sera. The range of antibody activity for 133 persons unlikely to have experienced gonorrhea was 0.1-1.6 mug/ml with a geometric mean of 0.5 mug/ml. This geometric mean antibody activity was significantly lower than the geometric mean for asymptomatically infected males (1.0 mug/ml, P < 0.002), males with symptomatic gonococcal anterior urethritis (1.6 mug/ml, P < 0.001), or asymptomatically infected females (4.2 mug/ml, P < 0.001). Antibody appeared in elevated levels (> 1.6 mug/ml) 2-3 wk after infection and returned toward control levels 1 or more months after treatment. Antibody levels higher than 1.6 mug/ml were found in 26 (50%) of 52 males with gonococcal anterior urethritis, in 10 (33%) of 30 males with asymptomatic urethral infection and in 50 (89%) of 56 asymptomatically infected females. In a high-risk group of 103 females for whom culture results and antibody to pili were compared, 58 (57%) had elevated antibody levels to pili and 86% of the infected females were within this seropositive group. The antigen binding assay may provide a means to detect asymptomatic gonococcal infection in women.

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

Carbon dioxide fixation in skin.

Carbon dioxide has been known for some time to be one of the products of carbohydrate metabolism. More recently it has been demonstrated that CO2 is utilized in pathways of carbohydrate synthesis. Five reactions have been described by which CO2 is incorporated into citric acid intermediates. Two important functions of CO2 fixation reactions have been suggested. Citric acid cycle intermediates can be generated by the fixation reactions and schemes utilizing two of the reaction will reverse the pyruvic kinase reaction. The latter is a step essential to glucogenesis. This paper shows that carbon dioxide fixation occurs in rat skin. The labeling pattern of oxaloacetate after fixation is consistent with patterns predicted by either the malic enzyme or propionyl carboxylase fixation reactions. The presence of the phosphopyruvic carboxykinase and pyruvic carboxylase reactions cannot be definitely ruled out by the experimental data. More work on the enzymatic level should show the significance of these various fixaon reactions in skin. Further experiments may also elucidate a relationship between factors known to affect the fixation reactions which also produce gross and microscopic changes in skin.

Pseudogranuloma inguinale caused by haemophilus ducreyi.

We used a new selective culture medium to isolate Haemophilus ducreyi from a penile ulcer that had the clinical appearance of granuloma inguinale. The isolation of the organism in pure culture permitted us to make a definitive diagnosis and obtain antimicrobial susceptibility data in a relatively short period. As a result, we were able to change therapy from sulfamethoxazole to erythromycin, and the infection rapidly healed.

Chancroidal ulcers that are not chancroid. Cause and epidemiology.

Hemophilus ducreyi was isolated from the ulcer of one of 33 patients in whom chancroid had been diagnosed clinically. Herpes simplex virus was isolated from 16 of these patients. A presumptive diagnosis of chancroid was made in one of three sexual partners of the only index patient with culture-proved chancroid. No chancroidal lesions were found in any of 39 sexual partners of the other 32 index patients. Genital cultures for herpes simplex virus were positive from four of 14 sexual partners of index patients with genital herpes simplex infection. The differential diagnosis of chancroidal genital ulcers is facilitated by herpes simplex virus cultures and a new selective H ducreyi culture medium.

Evaluation and management of acute genital ulcers in sexually active patients.

The causes of genital ulcers vary with the age of the patient. Although sexually related genital ulcers can be seen at any age, they are most common between the ages of 15 and 30. The differential diagnosis includes syphilis, chancroid, genital herpes, lymphogranuloma venereum, granuloma inguinale, fixed drug reactions, and traumatic ulcers.

Genitourinary imaging in children.

Genitourinary imaging in children has gone through a metamorphosis in the past 30 years, paralleling technical advances in sonography, CT scanning, and MR imaging. The imaging sequences for hydronephrosis and UTI are still controversial and require outcomes analysis to determine which studies are most beneficial and efficacious.

A combination benzoyl peroxide and clindamycin topical gel compared with benzoyl peroxide, clindamycin phosphate, and vehicle in the treatment of acne vulgaris.

A topical gel combining 5% benzoyl peroxide and 1% clindamycin as phosphate was evaluated in a 10-week randomized double-blind trial involving 287 patients with moderate to moderately severe acne. The combination agent demonstrated significantly greater reductions in inflammatory lesions than either of its active constituents (5% benzoyl peroxide and 1% clindamycin) or vehicle when used alone. Significantly greater reductions in comedos and improvements, as measured by both physicians' and patients' global evaluations, were obtained with the combination agent than with clindamycin or vehicle. The reduction in comedos and the global improvements were similar between the combination agent and benzoyl peroxide. The combination agent was well tolerated; the incidence of dry skin was similar to that found with benzoyl peroxide, and other adverse events were similar to that with vehicle. The improved efficacy obtained with combination therapy was accompanied by a safety profile similar to that of either constituent used alone.

Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected wounds.

BACKGROUND: Topical antimicrobials have been considered for treatment of secondarily infected wounds because of the potential for reduced risk of adverse effects and greater patient convenience. We compared mupirocin cream with oral cephalexin in the treatment of wounds such as small lacerations, abrasions, or sutured wounds. METHODS: In 2 identical randomized double-blind studies, 706 patients with secondarily infected wounds (small lacerations, abrasions, or sutured wounds) received either mupirocin cream topically 3 times daily or cephalexin orally 4 times daily for 10 days. RESULTS: Clinical success at follow-up was equivalent in the two groups: 95.1% and 95.3% in the mupirocin cream and the cephalexin groups, respectively (95% confidence interval [CI], -4.0% to 3.6%; P = .89). The intention-to-treat success rate was 83% in both groups. Bacteriologic success at follow-up was also comparable: 96.9% in the mupirocin cream and 98.9% in the cephalexin groups (95% CI, -6.0% to 2.0%; P = .22). The occurrence of adverse experiences related to study treatment was similar for the 2 groups, with fewer patients in the mupirocin cream group reporting diarrhea (1.1% vs 2.3% for cephalexin). CONCLUSIONS: Mupirocin cream applied topically 3 times daily is as effective as oral cephalexin given 4 times daily for the treatment of secondarily infected wounds and was well tolerated.

Diagnosis and management of acute genital ulcers in sexually active patients.

Sexually transmitted genital ulcer diseases include herpes simplex, chancroid, granuloma inguinale, lymphogranuloma venereum, and syphilis. Each of these infections has a characteristic clinical picture, but an accurate diagnosis usually requires the support of laboratory tests. The diagnosis will determine the appropriate therapy as well as sexual partner management.