Prophylaxis against gonorrhea: is an ounce of prevention worth the cost?
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Biomedical subjects
Publications and source records attributed to W O Harrison.
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Between 1974-1978, a study group 970 mineworkers exposed from before July 1962 only to Cape crocidolite were traced: 755 were alive and 215 dead. Of those still alive, 66.1% showed no radiological abnormalities of the chest; 8.9% had irregular small opacities only; 17.7% had pleural abnormalities only; and 7.3% had both. Five pleural mesotheliomas were found in living ex-workers; although only one was reported in those who had died, this was considered to be an underestimate. The incidences of pleural mesotheliomas in ex-employees of the mining industry outside of the study group are also described.
Gonococci that resist standard penicillin regimens by production of a penicillinase are now well established in certain areas of the world. Because cefoxitin, a semisynthetic cephamycin, resists gonococcal penicillinase in vitro, we compared procaine penicillin G and cefoxitin in treatment of gonorrhea in an area where 40 per cent of isolates produce penicillinase. One hundred and seven men with culture-proved gonococcal urethritis were given a single dose of either procaine penicillin G, 4.8 million U, or cefoxitin, 2 g, intramuscularly. Both groups took 1 g of probenecid orally; cefoxitin was given with lidocaine to reduce pain at the injection site. In men infected with penicillinase-negative gonococci, both cefoxitin and penicillin were highly effective. Penicillin failed in 77 per cent of men with penicillinase-positive strains, whereas cefoxitin was completely successful. Cefoxitin is an effective alternative to spectinomycin for single-session therapy of urethritis caused by penicillinase-producing Neisseria gonorrhoeae.
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.
Fatal infectious endocarditis involving a left ventricular apicoaortic valve-bearing conduit occurred in a 20-year-old man. Risk factors included early postoperative wound infection, broad spectrum suppressive antibiotic administration, and inadequate dental prophylaxis against infectious indocarditis. Palliative therapy included intravenous antibiotic administration and removal of the conduit. Lessons learned are discussed.
Cefaclor is a cephalosporin antibiotic whose chemical structure is similar to that of cephalexin. The substitution of a chloro group for the methyl group of cephalexin has produced a compound with markedly improved antibacterial activity, while retaining the property of gastrointestinal absorption. Cefaclor has shown good in vitro activity against Neisseria gonorrhoeae. In a controlled clinical trial, 40 men with uncomplicated gonococcal urethritis received cefaclor given as a one gram loading dose, followed by 500 mg 4 times daily for 3 days, for a total dose of 7 g. All patients were re-evaluated at 3 to 7 days following completion of therapy. Two patients did not complete the entire course of therapy and were eventually treated with another regimen. Of 38 men who took the full course of therapy, 35 were clinically and bacteriologically cured. Two men were clinically infected but had negative pretreatment cultures. Of 19 men with beta-lactamase-positive gonococcal urethritis, 18 were cured, whereas among 17 men with penicillin-sensitive strains, all were cured. There were no adverse reactions to the drug, and all patients expressed a preference for the oral regimen. The success of cefaclor in this pilot study suggests that additional clinical trials should be performed.
Many laboratory tests have been recommended for monitoring factory workers exposed to lead. To select the most useful test the best predictor of selected measures of morbidity was sought. 639 lead-exposed workers in several factories were questioned about abdominal ache, constipation, and fatigue and were examined for hand tremot. Packed-cell volume, blood-lead, urinary lead, and delta-aminolaevulinic acid were estimated in 489 workers. About half of the values for the latter three tests fell into the "excessive" or "dangerous" category of lead absorption. Blood-lead was a better predictor of morbidity than any other laboratory test, and further information did not add appreciably to morbidity prediction. The findings suggest that blood-lead measurement is the most meaningful test for monitoring workers exposed to lead. The effect of lead on morbidity does not appear to depend on its action on the porphyrin metabolic pathway.
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.
In October 1974, a large foodborne outbreak of hepatitis occurred among naval personnel undergoing basic training at the Naval Training Center, San Diego, California. Of the 2781 recruits eating at the implicated dining hall on the day disease transmission occurred, 133 developed clinical or laboratory evidence of hepatitis for an attack rate of 47.8/1000. The epidemiologic investigation suggested that hepatitis A virus was the etiologic agent, and this was subsequently confirmed by laboratory examination. The index and source case was a recuit food-handler who experienced prodromal symptoms of hepatitis while preparing salads and fresh fruit 32 days prior to the outbreak. A food preference questionnaire implicated tossed salad and fresh grapefruit as the specific vehicles of transmission.
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The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone.
Immune electron microscopy, which can detect hepatitis A antigen and antibody (anti-HA), was used to study a foodhandler-associated outbreak of hepatitis among 136 naval recruits. In stool specimens collected during the acute phase of illness, 27-nm viruslike hapatitis A antigen particles were shown, but only in patients with icteric hepatitis. Detection was possible in stools collected as early as 10 days before peak serum aminotransferase activity and up to the time of peak enzyme activity, but not thereafter. The immunologic similarity of these viruslike particles to those found in acute phase stools of volunteers inoculated with the MS-1 strain of hepatitis A virus was determined, and an increase in anti-HA was shown between acute and convalescent serums from 25 of the recruits. These data support the view that the MS-1 strain of hepatitis A virus is serologically related to naturally acquired type A hepatitis.
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Therapy of disease caused by penicillinase-producing Neisseria gonorrhoeae with lower-than-standard doses of cefoxitin was evaluated. A pilot study showed that doses of greater than or equal to 1 g were adequate, whereas 500-mg doses consistently failed. After the pilot study, 89 men with gonorrhea were treated with 1 g of cefoxitin given intramuscularly plus 1 g of probenecid given orally. Of the 89 men, 86 were cured. Sixty per cent were infected with penicillin-resistant strains of N. gonorrhoeae. The three men who were culture-positive on follow-up had been sexually reexposed, whereas none of those with negative cultures had had reexposure. These clinical results indicate that a treatment regimen of 1 g of parenteral cefoxitin plus 1 g of oral probenecid appears to be as effective as the standard 2-g dose. Regimens using doses lower than 1 g are ineffective.
Fifty-five men with culture-proved gonococcal urethritis caused by either penicillin-sensitive or penicillinase-producing Neisseria gonorrhoeae were treated with 1 g of ceftizoxime given intramuscularly. All patients were cured, including 26 (47%) with penicillinase-producing strains. Patients experienced no local or systemic side effects and tolerated the injection of ceftizoxime well. These results show that ceftizoxime is an effective alternative to either spectinomycin or cefoxitin in treatment of uncomplicated gonococcal urethritis caused by penicillin-resistant bacteria.
When combined with penicillin, sulbactam, a beta-lactamase inhibitor with weak intrinsic antibacterial activity, produces a marked synergistic effect in vitro against penicillinase-producing Neisseria gonorrhoeae. We compared a regimen of aqueous procaine penicillin G, sulbactam, and probenecid with spectinomycin for the treatment of uncomplicated gonococcal urethritis. Of 101 patients receiving the penicillin-sulbactam regimen, 97 (97%) were cured of their infection, as were 87 (95%) of 92 patients who received spectinomycin. Fifty per cent of patients were infected with penicillinase-producing N. gonorrhoeae; 43 (94%) of 46 treated with the penicillin-sulbactam regimen were cured as compared with 47 (92%) of 51 treated with spectinomycin. Neither regimen was associated with serious adverse effects. The results show that aqueous procaine penicillin G given with sulbactam and probenecid is an effective alternative for single-session therapy of urethritis caused by penicillinase-producing N. gonorrhoeae.
Aqueous procaine penicillin, ampicillin, and amoxicillin have been used successfully in treatment of gonococcal infections for many years. Many of the new beta-lactam antimicrobial agents subsequently have proved effective for treating these infections as well. First-generation cephalosporins are less active (by weight) than second-generation cephalosporins, which, in turn, are less active than third-generation drugs. Single-dose therapy of uncomplicated mucosal gonococcal infections with first-generation cephalosporins has resulted in generally unacceptably low cure rates of less than 90% in most studies, whereas parenterally and orally administered second-generation cephalosporins show good clinical efficacy. Both second- and third-generation cephalosporins are active against beta-lactamase-producing Neisseria gonorrhoeae. The extended-spectrum and ureido-penicillins are active in vitro against non-beta-lactamase-producing N. gonorrhoeae and have parallel activity in vivo. Single doses of aztreonam, the first monobactam studied in humans, have also shown excellent clinical efficacy.
During a 1974 foodborne outbreak of viral hepatitis type A among Navy recruits, we evaluated clinical and laboratory features prospectively in 130 affected persons. The ratio of anicteric to icteric persons identified during the outbreak was 1:3.5 but illness was relatively mild in this population of young adults. Infrequently reported in association with type A hepatitis, rash and arthralgias (but not arthritis) were reported by 14 and 10% of affected persons, respectively. Fourteen weeks after onset of acute illness, 8.5% of patients had persistently elevated aminotransferase activities and underwent percutaneous liver biopsy. Morphologic features included piecemeal necrosis, but clinical, biochemical, and histological evidence of disease resolved within five months to one year after the outbreak. Fecal shedding of hepatitis A virus began during the preicteric stage, did not persist beyond the second day of jaundice (even in patients with protracted illness), and was not detected in anicteric patients. Feces and serum obtained during the late incubation period, but not urine, were infectious in chimpanzees. Antibody to hepatitis A virus developed during convalescence, and serum anticomplementary activity was noted during acute illness. Failure of T-lymphocytes to bind sheep erythrocytes and form rosettes was observed, was found to be modulated in several cases by an intrinsic lymphocyte defect and in others by the presence in serum of an extrinsic immunoregulatory serum lipoprotein, "rosette inhibitory factor," which persisted in patients with slow resolution.