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Biomedical subjects

J P Bryan

Publications and source records attributed to J P Bryan.

36 records · Page 2Linked to original sources

The prevalence of hepatitis A, B and C infection among different ethnic groups in Belize.

Little is known about the prevalence of infection with hepatitis viruses in Belize, Central America. We conducted a serologic survey among members of the Belize Defence Force (BDF), which is composed of the five major ethnic groups in Belize, to estimate prevalence rates of hepatitis A, B, and C among military-aged men and women in Belize. Of approximately 600 men and women in the BDF, 492 (82%) completed a questionnaire and blood collection. Antibody to hepatitis A was found in 94%, with similar rates by age, sex, rank, and ethnicity. Antibody to hepatitis B core antigen (anti-HBc) was found in 31%. Rates of anti-HBc varied significantly among the ethnic groups with the lowest rates in Mestizo (5%) and Mayan Indians (9%), and significantly higher rates among Creoles (30%) and Garifuna (56%). Rates increased with increasing age from 28% in those 18-24 years old to 35% in those > or = 35 years old (P = 0.07, by chi-square test for trend). Hepatitis B surface antigen was found in 21 (4%) overall. Antibody to hepatitis C was found in two (0.4%). In this young healthy population, exposure to hepatitis A before the age of 18 is almost universal, while exposure to hepatitis B is related to age and ethnic origin.

Adult↗

Association of hepatitis E virus with an outbreak of hepatitis in Pakistan: serologic responses and pattern of virus excretion.

Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV-infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice.

Antibodies, Viral↗

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose.

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Low-dose intradermal and intramuscular vaccination against hepatitis B.

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Hepatitis B↗

Therapy of experimental meningitis due to Salmonella enteritidis.

In many areas of the developing world, Salmonella spp. account for greater than 50% of the gram-negative enteric organisms isolated from cerebrospinal fluid (CSF). The response of Salmonella meningitis to conventional therapy (chloramphenicol and/or ampicillin) is slow, complications arise frequently, and mortality rates of 60 to 80% are common. Two newer agents, ceftriaxone and imipenem, were compared with ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (TMP-SMX) in the therapy of experimental Salmonella meningitis beginning 14 h after intracisternal inoculation and continued by constant intravenous infusion for 8 h. Drug concentrations in serum and CSF closely approximated those achieved in the sera and CSF of humans receiving standard parenteral regimens. Penetration into purulent CSF [(concentration of drug in CSF/concentration of drug in serum) x 100] ranged from 18 to 41%. The rate of bacterial killing in CSF was significantly (P less than 0.001) more rapid during therapy with ceftriaxone and imipenem than it was during therapy with chloramphenicol or TMP-SMX. Ceftriaxone and imipenem sterilized the CSF of six of seven animals at 8 h, whereas it sterilized the CSF of three of eight animals treated with ampicillin (P = 0.18), one of eight animals treated with chloramphenicol, and none of seven animals treated with TMP-SMX (P less than or equal to 0.01; ceftriaxone or imipenem versus chloramphenicol or TMP-SMX). New beta-lactams, including ceftriaxone and imipenem, appear to be effective therapy against Salmonella spp. in this animal model and deserve further evaluation in humans.

Animals↗

In vitro activity of tosufloxacin (A-60969) and clarithromycin (A-56268, TE-031) against resistant Haemophilus influenzae, Streptococcus pneumoniae and Branhamella catarrhalis isolates.

The activity of tosufloxacin (A-60969), a new oral quinolone, and clarithromycin (A-56268, TE-031), a new oral macrolide, was compared in vitro to that of other oral quinolones and beta-lactam antimicrobial agents against clinical isolates of ampicillin and/or chloramphenicol resistant Haemophilus influenzae, penicillin resistant Streptococcus pneumoniae and beta-lactamase producing Branhamella catarrhalis. Results were compared to those for sensitive isolates. Tosufloxacin was the most active compound against Haemophilus influenzae and was more active than ciprofloxacin or ofloxacin against all strains of Streptococcus pneumoniae. Tosufloxacin was also more active than any of the beta-lactam drugs tested against penicillin resistant or relatively penicillin resistant isolates. Clarithromycin was the most active compound tested against both penicillin sensitive and penicillin resistant Streptococcus pneumoniae, and was as active as ciprofloxacin against Branhamella catarrhalis. In view of the favourable in vitro activity against common bacterial respiratory pathogens, tosufloxacin should be considered for clinical trials in adults with respiratory tract infections, while clarithromycin might be useful in treatment of infection with these organisms in all age groups.

4-Quinolones↗

Comparative trial of low-dose, intradermal, recombinant- and plasma-derived hepatitis B vaccines.

The immunogenicity and reactogenicity of low-dose, recombinant DNA and plasma-derived hepatitis B vaccines were investigated in a prospective, double-blind, randomized, controlled trial. Volunteers (153) received either recombinant vaccine, 10 micrograms in 1 ml intramuscularly; plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally or recombinant vaccine, 1 microgram in 0.1 ml intradermally at 0, 30, and 150 days. Peak geometric mean concentrations of antibody to hepatitis B surface antigen at day 200 were 1094, 387, and 43 mIU/ml, respectively. By day 360, these concentrations had fallen to 346, 124, and 19 mIU/ml, respectively (P less than .05 between groups both dates). Number of subjects with antibody greater than or equal to 10 mIU/ml at day 200 was similar between the 10-micrograms recombinant and 2-micrograms plasma-derived groups (94% vs. 90%), while only 78% of the 1-microgram recombinant group had protective concentrations of antibodies (P less than .05). Erythema and induration occurred in most subjects in both intradermal groups, while pain was prominent at the intramuscular site especially after the second dose. Thus, plasma-derived vaccine, 2 micrograms in 0.1 ml intradermally, appears to be an acceptable cost-saving method for hepatitis B immunization, while recombinant-derived vaccine, 1 microgram in 0.1 ml intradermally, produced less satisfactory results.

Adult↗

In vitro activities of tosufloxacin, temafloxacin, and A-56620 against pathogens of diarrhea.

Tosufloxacin (A-60969 HCl), a new quinolone with broad activity against gram-positive and anaerobic organisms, was compared in vitro with other quinolones against bacterial pathogens of diarrhea. Tosufloxacin was the most active agent against Salmonella spp., Shigella spp., Campylobacter spp., Aeromonas hydrophila, and Vibrio spp. Temafloxacin (A-62254) also demonstrated good activity against these organisms.

Anti-Bacterial Agents↗

Oral ciprofloxacin versus ceftriaxone for the treatment of urethritis from resistant Neisseria gonorrhoeae in Zambia.

Neisseria gonorrhoeae strains resistant to treatment with penicillin, tetracycline, and/or spectinomycin are increasing in prevalence in many parts of the world. In Zambia, 52% of N. gonorrhoeae isolates produced beta-lactamase in 1986. Few oral regimens have proven effective for treatment of resistant N. gonorrhoeae. We conducted a prospective, double-blind, randomized clinical trial of 250 mg of ciprofloxacin given orally versus 250 mg of ceftriaxone given intramuscularly for treatment of uncomplicated gonococcal urethritis in adult males. Two hundred men were enrolled and treated. The two groups were comparable in age (27.5 years), prevalence of latent syphilis (14 and 10%), and human immunodeficiency virus infection (32 and 38%). Of 165 patients with cultures positive for N. gonorrhoeae who returned for follow-up, ciprofloxacin cured 83 of 83 (100%), including 26 with penicillinase-producing N. gonorrhoeae (PPNG) and 21 with N. gonorrhoeae with chromosomally mediated resistance to multiple antibiotics (CMRNG), and ceftriaxone cured 81 of 82 (98.7%), including 30 with PPNG and 19 with CMRNG. Both treatment regimens were well tolerated. Chlamydia trachomatis in urethral exudate was found by direct fluorescent-antibody microscopic examination or by culture in 10 (5%) participants. All N. gonorrhoeae isolates were inhibited by ceftriaxone at 0.06 micrograms/ml, except one which was inhibited at 0.125 micrograms/ml, while ciprofloxacin inhibited all isolates at 0.03 micrograms/ml. Ciprofloxacin is a safe and effective therapy for uncomplicated gonococcal urethritis, including that caused by PPNG and CMRNG in human immunodeficiency virus-infected men.

Adult↗

Prevalence of concurrent Chlamydia trachomatis infections among men with gonococcal urethritis in Lusaka.

The prevalence of Chlamydia trachomatis infections among male patients with gonococcal urethritis in the sexually transmitted diseases (STDs) clinic at UTH, Lusaka, was determined by two methods to be around 4.7%. Methods used were specific for C. trachomatis (Syva Microtrak), and second isolation of C. trachomatis. The results indicate that with a prevalence rate of 4-7% for concurrent gonococcal and chlamydial infection, it is not financially or medically practical to treat all cases of gonorrhoea in Zambia for possible chlamydial infection, as is advocated in some countries. The findings further suggest that the commercially available Syva Microtrak test should probably be considered positive when one or two monoclonal-stained elementary bodies are seen, rather than ten, to avoid false-negative results.

Chlamydia Infections↗

An outbreak of enterically transmitted non-A, non-B hepatitis in Pakistan.

An epidemic of enterically transmitted non-A, non-B hepatitis occurred at a college in Sargodha, Pakistan in early 1987. There were 133 clinical cases, an attack rate of approximately 20%. Though the disease was relatively mild, all clinical cases required hospitalization and prolonged convalescence. Nearly all cases were associated with a single water source. The epidemic ended when the water supply was improved. This is the 4th described epidemic of non-A, non-B hepatitis in Pakistan.

Acute Disease↗

Intracranial blastomycoma.

Although meningitis is the most common form of central nervous system (CNS) blastomycosis, solitary mass lesions are not an infrequent presentation. Four of our patients presented with focal neurological deficits as a result of single intracranial mass lesions. Only 1 had clearcut evidence of extraneural blastomycosis. One was a coal miner, another worked with soil samples, and one was an engineer for a wood pulp company. All were previously healthy and 2 had diabetes. Complement fixation and immunodiffusion tests were negative in all 4 patients, and white blood cell counts and erythrocyte sedimentation rates were normal. Wet mount of tissue obtained intraoperatively by aspiration demonstrated the organism in 2 cases, culture from a lung lesion made the diagnosis in 1 case, and stain and culture of ventricular fluid revealed the organisms in the fourth case. Multiple cultures of cerebrospinal fluid from lumbar puncture were negative. All 4 patients survived. Amphotericin B alone was curative in 2 cases; surgical removal alone was curative in 1. All 4 computerized tomographic scans revealed isodense or slightly hyperdense single mass lesions with homogeneous contrast enhancement and surrounding edema, and tumor was the preoperative diagnosis in 2 cases. Such scans should suggest CNS blastomycoma in patients from the endemic area, despite the lack of other systemic manifestations. Diagnosis nevertheless rests on the characteristic histopathologic appearance in tissues and/or culture. Solitary intracranial blastomycomas may be less rare than previously thought; at our institution, we observed 4 cases in 4 years.

Adult↗

Haemophilus paraphrophilus endocarditis.

We have described a previously healthy medical student who had endocarditis due to Haemophilus paraphrophilus necessitating replacement of the mitral valve. We compared this case to the 11 previously reported cases of endocarditis caused by this organism, stressing the fastidious nature of the organism, its destructive nature, and its propensity for thromboembolism.

Adult↗

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis.

Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.

Ampicillin↗

Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis.

Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis. The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H. influenzae, and E. coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging. Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.

Animals↗

Etiology and mortality of bacterial meningitis in northeastern Brazil.

Little is known of the current incidence and mortality of meningitis in developing nations, especially in Latin America. We reviewed all cases of meningitis in an isolation-fever hospital in Salvador, Brazil, for the decade 1973-1982. Of all admissions, 6,751 (27%) were for meningitis; 4,100 (61%) of these cases were of definite or probable bacterial etiology. Children younger than 15 years accounted for 79% of cases, and 45% of cases were in children under 2 years. The overall case fatality rate was 33%, with 50% of these deaths occurring within 48 hours of hospitalization. Neisseria meningitidis was the etiologic agent in 32% of the cases, with a case fatality rate of 14%. Epidemics caused by N. meningitidis group C, then group A, in 1974-1978 accounted for 60% of the cases. Streptococcus pneumoniae caused 17% of cases, with a case fatality rate of 59%. Haemophilus influenzae type b, the most common cause of nonepidemic meningitis, caused 23% of all cases, with a case fatality rate of 38%. Enterobacteriaceae were the etiology in only 3.6% of patients, but the case fatality rate was 86%. Cultures were negative in 18% of cases with purulent cerebrospinal fluid. A total of 84% of H. influenzae, 40% of S. pneumoniae, 78% of Enterobacteriaceae, and 15% of N. meningitidis cases occurred in children less than 2 years of age. Case fatality rates were highest in this group. Vaccines protective for this age group are urgently needed.

Adolescent↗

Problems in salmonellosis: rationale for clinical trials with newer beta-lactam agents and quinolones.

Disease syndromes caused by Salmonella species continue to be important, as evidenced by a major outbreak of infection due to multiresistant Salmonella typhimurium in 1985; this outbreak involved more than 12,000 people in five north-central states of the United States. Salmonella species have become progressively more resistant in recent years to the clinically useful antibiotics (trimethoprim-sulfamethoxazole, ampicillin, and chloramphenicol). The clinical experience accumulated thus far indicates that two new classes of antimicrobial agents, the third-generation cephalosporins and the quinolones, offer significant potential for the treatment of specific problems in salmonellosis: bacteremia and enteric fever, meningitis, osteomyelitis, and the chronic carrier state.

Ampicillin↗