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Biomedical subjects

E C Tramont

Publications and source records attributed to E C Tramont.

At least 37 records · Page 2Linked to original sources

Studies in volunteers to evaluate candidate Shigella vaccines: further experience with a bivalent Salmonella typhi-Shigella sonnei vaccine and protection conferred by previous Shigella sonnei disease.

A bivalent vaccine consisting of Salmonella typhi strain Ty21a containing the 120 MDa plasmid of Shigella sonnei and expressing both S. typhi and S. sonnei lipopolysaccharides (LPS) on its surface was previously shown to protect significantly against S. sonnei disease in experimental challenge studies. However, protective efficacy could not be reconfirmed in volunteers with five subsequent lots of vaccine. One vaccine lot which resembled the initial protective lots of vaccine in biochemical and serological tests, and by electron microscopy, was administered to 16 volunteers who ingested three doses of 10(9) organisms each. Antibody secreting cells (ASC) specific for S. sonnei LPS were detected in the blood of 100% of vaccines, but no protection of these vaccines was demonstrated during a S. sonnei challenge study. To assess the ability of the volunteer model to detect infection-derived immunity, six volunteers who had had clinical shigellosis due to S. sonnei two months earlier were rechallenged with wild-type S. sonnei, together with 12 controls. Prior infection provided 100% protection against febrile illness (p = 0.05) and diarrhea (p = 0.04), thereby validating the volunteer model for assessing Shigella vaccines.

Administration, Oral↗

Prescription drug use patterns of human immunodeficiency virus-infected patients taking zidovudine. Walter Reed Retrovirus Research Group.

Prescription drug profiles of 116 human immunodeficiency virus (HIV)-infected patients taking zidovudine in 1988 were surveyed. Patients received the drug an average of 236 days. About one-third (32 percent) required reduced dosage presumably because of hematologic toxicity and this was associated with length of time on the drug. Zidovudine dosage reduction was not associated with concurrent therapy with either acetaminophen or acyclovir. Concomitant drug therapy was common, especially with systemic antifungals (47 percent), antivirals (33 percent), nonsteroidal antiinflammatory drugs (23 percent), and antidepressants (20 percent), as well as topical fungicides (35 percent) and antiinflammatory agents (28 percent). Over three-fourths of patients on zidovudine were on chemoprophylaxis for Pneumocystis carinii pneumonia, most often with pentamidine inhalation therapy. This study showed that the HIV-infected patient population is being treated concomitantly with many pharmacologic agents prescribed by various medical specialties.

Acquired Immunodeficiency Syndrome↗

Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae.

Because of the high prevalence of penicillinase-producing Neisseria gonorrhoeae in the Republic of Korea, spectinomycin has been used there in the primary treatment of gonococcal infections in U.S. military personnel since 1981, but there have been increasingly frequent reports of treatment failures with spectinomycin. We conducted a clinical study to determine the efficacy of spectinomycin treatment in 124 U.S. servicemen in the Republic of Korea who had urethral gonococcal infections. Ninety-seven patients were treated with spectinomycin alone and evaluated in a follow-up visit. In eight patients (8.2 percent), this treatment was unsuccessful. Antibiotic-sensitivity testing on isolates from seven of the patients with treatment failure demonstrated that six isolates were highly resistant to spectinomycin (minimal inhibitory concentration, greater than or equal to 100 micrograms per milliliter). None of the spectinomycin-resistant strains had become resistant to penicillin, either through the production of penicillinase or through a chromosomal mutation. Although the mechanism of spectinomycin resistance appears to be a chromosomal mutation, these isolates were generally sensitive to other antibiotics. The prevalence of resistance to spectinomycin resulted in the substitution of ceftriaxone for the primary treatment of gonorrhea acquired by U.S. military personnel in the Republic of Korea. We believe that the rapid emergence of spectinomycin resistance in this population mandates a cautious approach to widescale use of the drug and indicates a need to broaden current surveillance programs.

Adolescent↗

Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma. A diagnostic dilemma.

Reagin and treponemal antibody tests are highly reliable in diagnosing secondary syphilis. However, patients infected with the human immunodeficiency virus (HIV) respond abnormally to antigenic stimulation and may fail to develop typical serologic responses to infections. We report the case of an HIV-infected man with Kaposi sarcoma and secondary syphilis whose VDRL test and fluorescent treponemal antibody-absorbed test were repeatedly nonreactive. Correct diagnosis required biopsy of a skin lesion with silver staining to show spirochetes. Clinicians treating HIV-infected patients should be aware of the problems of serologic diagnosis of syphilis in these patients. Biopsy samples of appropriate tissues and staining for spirochetes may be needed to arrive at the correct diagnosis.

Acquired Immunodeficiency Syndrome↗

Pilus vaccines.

Bacterial pili (fimbriae) are protein appendages which extend from the cell surface and serve to adhere the microorganism to body surfaces. These appendages have been isolated, purified and characterized as vaccine candidates. These vaccines stimulate an immune response which serves at least with regards to Neisseria gonorrhoeae to block the adherence of the microorganism to epithelial cells. Thus far, these vaccines have proven effective in some animal studies and in a limited number of human challenge studies. The problems that remain are: lack of broad cross reactivity of the vaccines thus far developed poor immunogenicity of the important binding ligands both in terms of quality and quantity of antibody produced and inadequate stimulation of antibody response at the local site of infection.

Animals↗

Oral amoxycillin, an alternative treatment for neurosyphilis.

A serum amoxycillin concentration of 0.11 g/l was established as being treponemicidal in a rabbit model with orchitis. Seventeen patients treated with amoxycillin 2 g by mouth three times a day plus 500 mg probenecid twice a day attained treponemicidal CSF amoxycillin concentrations. Thus amoxycillin by mouth offers an effective alternative method for treating patients with neurosyphilis.

Administration, Oral↗

American cutaneous leishmaniasis: a comparison of three sodium stibogluconate treatment schedules.

Thirty-six patients with American cutaneous leishmaniasis were randomized to receive intravenous sodium stibogluconate for 10 days at a dose of 600 mg antimony (Sb) per day by one of three schedules: once daily by rapid infusion (A), by continuous 24 hr infusion (B), or in divided doses every eight hours by rapid infusion (C). Patients not cured after initial treatment were rerandomized to one of the other treatment schedules. An additional 19 patients who were not part of the randomized study received standard (STD) sodium stibogluconate treatment (600 mg Sb once daily by rapid infusion for 10 days, identical with schedule A). In the randomized study, the overall cure rate after the first course of treatment was 64%, but was higher for schedule A (100%) than for B (50%) or C (42%) (P less than 0.01). Considering all courses of treatment, schedule A was more effective (94%) than B (53%) or C (43%) (P less than 0.01). Paradoxically, patients in group A had a higher cure rate than patients in group STD (42% after the first course of treatment and 51% when all courses of treatment were considered). Side effects were mild and well tolerated. Total side effects were more frequent in groups B + C (52%) than A + STD (23%) due to an increased incidence of subjective complaints (26% vs. 10%, P less than 0.05) in patients receiving other than once daily rapid infusion. We conclude that giving the same total amount of sodium stibogluconate in three divided doses or by continuous infusion offers no advantage over standard, once daily treatment of American cutaneous leishmaniasis.

Antimony Sodium Gluconate↗

Safety and antigenicity of typhoid-Shigella sonnei vaccine (strain 5076-1C).

The form-1 antigen of Shigella sonnei was transferred to the avirulent Salmonella typhi strain 21a and the resulting 5076-1C transconjugate strain was tested for safety and immunogenicity as a candidate oral vaccine. The transconjugant strain was shown to be well tolerated and safe in 19 human volunteers who were fed from 1 X 10(7) to 1 X 10(10) organisms. Only two of 10 volunteers tested had developed a rise in antibody titer to the lipopolysaccharide of the hybrid 5076-1C strain.

Administration, Oral↗

Genital antibody response to a parenteral gonococcal pilus vaccine.

A parenteral gonococcal pilus vaccine which has previously been shown to be safe and antigenic also results in the production of specific local genital antibody. All three major antibody classes were present in the local secretions, but immunoglobulin A predominated, a portion of which is dimeric 11S immunoglobulin A. This mucosal antibody is also capable of blocking the attachment of gonococci to epithelial cells. The antibody cross-reacted with five heterologous pili in a solid-phase radioimmunoassay. These results are encouraging and suggest that a gonococcal pilus vaccine may be efficacious in preventing gonorrhea.

Adult↗

Adhesion of Neisseria gonorrhoeae and disease.

Adhesion of gonococci to mucosal epithelial cells appear to be a critical step in the pathogenesis of gonococcal infection. Parameters affecting adhesion, the antigens involved in adhesion and the human antibody response that blocks adhesion have been studied. Gonococci adhere to a variety of human cells grown either in tissue culture or organ culture or scraped from mucosal surfaces. They adhere in greatest number to mucosal cells derived from sites of natural infection but buccal mucosal cells were used for most of these studies because of the ease of obtaining them, the homogeneous population obtained, and the similarity of the results of antibody studies with all cell types. The ability of a given strain of gonococci to attach to buccal cells (receptors) varied with the individual from whom the cells were obtained, and the capacity to support adhesion of a given strain fluctuated from day to day. The principal antigens mediating attachment are pili (filamentous protein appendages extending from the bacterial cell wall) which are antigenically heterogeneous. Lipopolysaccharide also blocks attachment but it is less efficient than pili and is not species-specific. Other antigens, probably proteins, also block attachment. Human antibody (both local and humoral) blocked the adhesion of gonococci. The antibody was directed against pili and the antigens in naturally occurring disease and could be induced by immunizing subjects with purified pili. The results of these studies suggest two new approaches to the prevention of gonorrhoea: (1) (competitive) inhibition of the adhesion with specific antigens, i.e. pili; and (2) immunization with purified attachment antigens to produce shielding antibodies.

Adhesiveness↗