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Biomedical subjects

A Ronald

Publications and source records attributed to A Ronald.

At least 37 records · Page 2Linked to original sources

A morphological study of penile chancroid lesions in human immunodeficiency virus (HIV)-positive and -negative African men with a hypothesis concerning the role of chancroid in HIV transmission.

Chancroid, the most common cause of genital ulceration in Africa, is known to be associated epidemiologically with heterosexual transmission of human immunodeficiency virus (HIV). The pathophysiological mechanisms by which chancroid might facilitate the spread of HIV are obscure. To investigate the role of chancroid in HIV transmission, the authors studied the histological features of biopsies from 11 men with penile chancroid lesions including five who were serologically positive for HIV. The histomorphologic and immunophenotypic nature of the inflammatory infiltrates suggests that there is a significant role for cell-mediated immunity in the host response to Hemophilus ducreyi infection. This response may be critical to the role of chancroid in HIV transmission.

Black or African American↗

Aberdeen polygons: computer displays of physiological profiles for intensive care.

The clinician in an intensive therapy unit is presented regularly with a range of information about the current physiological state of the patients under care. This information typically comes from a variety of sources and in a variety of formats. A more integrated form of display incorporating several physiological parameters may be helpful therefore. Three experiments are reported that explored the potential use of analogue, polygon diagrams to display physiological data from patients undergoing intensive therapy. Experiment 1 demonstrated that information can be extracted readily from such diagrams comprising 8- or 10-sided polygons, but with an advantage for simpler polygons and for information displayed at the top of the diagram. Experiment 2 showed that colour coding removed these biases for simpler polygons and the top of the diagram, together with speeding the processing time. Experiment 3 used polygons displaying patterns of physiological data that were consistent with typical conditions observed in the intensive care unit. It was found that physicians can readily learn to recognize these patterns and to diagnose both the nature and severity of the patient's physiological state. These polygon diagrams appear to have some considerable potential for use in providing on-line summary information of a patient's physiological state.

Adult↗

An immunohistochemical analysis of naturally occurring chancroid.

Haemophilus ducreyi is a major cause of genital ulcer disease in many developing countries and is associated with augmented transmission of human immunodeficiency virus (HIV). However, the mechanisms through which H. ducreyi produces ulceration are poorly understood. The characteristics of the host response to H. ducreyi and the pathobiology of its potential contribution to increased HIV susceptibility are not known. Chancroid ulcer biopsies from 8 patients were analyzed histologically and immunohistochemically. All biopsies had perivascular and interstitial mononuclear cell infiltrates that extended deep into the dermis. The infiltrate, which contained macrophages and CD4 and CD8 lymphocytes, was consistent with a delayed hypersensitivity type cell-mediated immune response. The recruitment of CD4 T lymphocytes and macrophages may in part explain the facilitation of HIV transmission in patients with chancroid.

Biopsy↗

Single dose treatment failure in women with acute cystitis.

Single dose treatment regimens (SDT) are effective, inexpensive alternatives to longer courses of therapy for adult females with acute cystitis or asymptomatic bacteriuria. A number of SDT regimens consistently cure 85 to 100% of women with acute cystitis and 50 to 80% of women with asymptomatic bacteriuria. However, SDT is inherently less effective than longer regimens because many upper tract infections are not cured. Initial SDT studies suggested that most patients with significant renal invasive disease or underlying urological abnormalities fail therapy. As a result, SDT has been proposed as an efficient strategy to diagnose significant upper tract infections with accompanying pathology that merit additional investigation or treatment. Few studies have refuted or supported this hypothesis. Single-dose treatment studies show an association between the site of infection as determined by the antibody-coated bacteria (ACB) test and treatment outcome. Patients with ACB-negative tests have a cure rate of over 90% in almost all studies in which the organism is susceptible to the agent chosen. Patients with positive ACB tests tend to have treatment failure rates of 30 to 50%. However, imaging studies have not been carried out in parallel with these studies and the validity of using single-dose treatment failure to screen women for significant upper tract pathology has still not been established.

Acute Disease↗

Treatment of acute pelvic inflammatory disease in the ambulatory setting: trial of cefoxitin and doxycycline versus ampicillin-sulbactam.

Ampicillin-sulbactam (750 mg) given orally twice daily for 10 days was evaluated for the treatment of acute pelvic inflammatory disease (PID) in an ambulatory setting in Nairobi, Kenya. The first 26 women received ampicillin-sulbactam in an open-label fashion, and the remaining 75 women were randomly selected to receive either ampicillin-sulbactam (n = 38) or cefoxitin (2 g) intramuscularly and probenecid (1 g) orally, followed by doxycycline (100 mg) orally twice daily for 10 days (n = 37). Women were enrolled in a sexually transmitted disease clinic and were followed for clinical and microbiologic responses at 1 to 2 weeks and 4 to 6 weeks posttreatment. Women had a later follow-up visit to note interim pregnancy or underwent hysterosalpingography for fertility outcome assessment. The short-term clinical response rates were 70% for ampicillin-sulbactam and 72% for cefoxitin-doxycycline (P = 0.47). Among Chlamydia trachomatis-infected women treated with ampicillin-sulbactam, three had microbiologic relapse. The post-PID tubal obstruction rates were similar in the two groups: 18% for ampicillin-sulbactam and 33% for cefoxitin-doxycycline (P = 0.31). Neither regimen was highly effective as a therapy for acute PID. These data strongly argue that primary prevention must be the goal for a reduction of PID morbidity and show that improved therapy for the treatment of PID in the ambulatory setting is needed.

Acute Disease↗

The Nairobi STD program. An international partnership.

Since 1980, Canadian, Belgian, and American scientists have been working together with colleagues in Kenya to understand the epidemiology and biology of sexually transmitted diseases (STDs) in Africa. The rapid spread of human immunodeficiency virus has dramatically increased the importance of this information. Interventions to slow the spread of all STDs and to reduce their consequences are now our major priority. However, this will require continuing research, ongoing training of scientists, epidemiologists, and technologists, and increasing financial support from industrialized societies.

Developing Countries↗

In-vitro activity of azithromycin, erythromycin, ciprofloxacin and norfloxacin against Neisseria gonorrhoeae, Haemophilus ducreyi, and Chlamydia trachomatis.

The minimum inhibitory concentrations (MICs) of azithromycin, erythromycin, ciprofloxacin and norfloxacin for 300 strains of Neisseria gonorrhoeae, 100 strains of Haemophilus ducreyi and six strains of Chlamydia trachomatis were determined. The two quinolones were more active against gonococcal strains than were the two macrolides. Azithromycin was approximately eight-fold more active against N. gonorrhoeae than was erythromycin (MIC90: 0.25 mg/l azithromycin, 2.0 mg/l erythromycin). The Mtr phenotype of gonococci increased azithromycin MICs approximately four fold. Azithromycin was less active than erythromycin against C. trachomatis. Azithromycin had considerable activity against H. ducreyi and was ten-fold more active than was erythromycin (MIC90: 0.004 mg/l azithromycin, 0.03 mg/l erythromycin). Clinical trials of azithromycin in the treatment of chlamydial infection and genital ulcer disease are indicated.

Azithromycin↗

In-vitro activity of meropenem against Neisseria gonorrhoeae, Haemophilus influenzae and H. ducreyi from Canada and Kenya.

Meropenem, a new parenteral carbapenem demonstrated increased activity as compared to imipenem against 336 strains of Neisseria gonorrhoeae, 119 strains of Haemophilus influenzae, and 110 strains of H. ducreyi. Neither carbapenem was affected by the beta-lactamase activity of the organisms tested. Ceftriaxone and ciprofloxacin demonstrated activity superior to that of both carbapenems while the activity of ceftazidime was similar to that of meropenem.

Anti-Bacterial Agents↗

An overview of some mechanisms of bacterial pathogenesis.

The adherence of microorganisms to host surfaces is highly specific, and in many cases, essential for subsequent pathogenetic events to occur. A dynamic process leading to increased mucosal adherence of gram-negative bacilli to epithelial cell receptors in the oral cavity appears to be the initial step in the development of pneumonia. In infectious processes secondary to Streptococcus pneumoniae, adherence may also play a role in specific syndromes. In many cases, however, colonization of oropharyngeal mucus itself, the presence of capsular polysaccharide, and the release of various cell wall components appear to interact to cause clinical disease. In Neisseria gonorrhoeae infections, adherence is all important and is mediated by a number of cell surface structures. These have been studied extensively. Many of these structures, such as pili and protein II, exhibit great variability both between strains and in the same organism at different stages of infection. Others, such as protein I, are more constant. This information has been used in the production of specific vaccines to more preserved structures to inhibit adherence. These will be tested in the near future. It is our view that a better understanding of the many forms of bacterial adherence will be the key to our designing more effective strategies to detect early infection and to intervene more decisively to limit its spread.

Bacteria↗

Laboratory diagnosis of Haemophilus ducreyi: sensitivity of culture media.

Laboratory confirmation of the clinical diagnosis of chancroid requires the isolation of Haemophilus ducreyi. Enriched gonococcal (GcHbS) and Mueller-Hinton agar (MHHb) both support the growth of most strains of H. ducreyi. In this study we compared the isolation rate of H. ducreyi on GcHbs and MHHb media in 111 men with genital ulcer disease. A second culture was obtained in 84 men at 48 hr in order to determine the reproducibility of H. ducreyi culture. The sensitivity of a single and a sequential pair of cultures on GcHbS was 67% and 74%, respectively, on men with presumed chancroid. The sensitivity of the MHHb as a single culture was 53%. Using both media for the initial culture of genital ulcers, and repeating the culture on GcHbs at 48 hr, increased the sensitivity of the isolation of H. ducreyi to 92% in men who had no prior antimicrobial use and who had no laboratory evidence of primary syphilis.

Chancroid↗

Trimethoprim sulphamoxole in the treatment of chancroid. Comparison of two single dose treatment regimens with a five day regimen.

In a prospective blinded study, 135 men with genital ulcers culture positive for Haemophilus ducreyi, were randomized to one of three regimens. Two single dose regimens, either the combination of sulphamoxole 3200 mg/trimethoprim 640 mg or trimethoprim 700 mg alone were compared to a five day regimen of sulphamoxole 800 mg/trimethoprim 160 mg twice daily. All 31 treated with a five day regimen of trimethoprim sulphamoxole healed without further treatment. Of 27 patients treated with the single dose sulphamoxole/trimethoprim regimen, only 21 were cured and of 34 treated with trimethoprim alone, 25 responded. Antibacterial susceptibilities were performed on 31 H. ducreyi isolates. The laboratory susceptibility of these strains to trimethoprim correlated with the clinical response to the single agent. Trimethoprim alone in a dose of 700 mg or the combination of sulphamoxole (3200 mg) and trimethoprim (640 mg) is not satisfactory for the single dose treatment of genital ulcer disease. However, when prescribed for five days, sulphamoxole/trimethoprim is effective and compares favourably with other treatment regimens.

Adult↗

Beta-lactams in sexually transmitted diseases: rationale for selection and dosing regimens.

A review is given of the selection and rational of optimal treatment regimens for patients with sexually transmitted pathogens, e.g. in cases of gonorrhea, chlamydial infections, chancroid, syphilis, pelvic inflammatory diseases and ophthalmia neonatorum. The scientific basis for the selection of a beta-lactam agent is discussed, including dose, MIC, the critical serum level and maintenance interval, and the duration of therapy. Except in the case of penicillinase-producing Neiserria gonorrhoeae, penicillin remained until recently the most effective agent available against many sexually transmitted diseases. However, ceftriaxone, a new third-generation cephalosporin, has been shown to have a long half-life (8 h) and excellent in vitro efficacy against Neiserria gonorrhoeae (including penicillinase-producing strains) and Haemophilis ducreyi. In view of its exceptional clinical efficacy against both gonorrhea and chancroid, clinical studies of its efficacy against other sexually transmitted diseases appear warranted.

Anti-Bacterial Agents↗

Comparative in vitro activity of norfloxacin against urinary tract pathogens.

The in vitro activity of norfloxacin (MK366) against 477 aerobic gram-negative and gram-positive clinical isolates was compared to that of nalidixic acid, nitrofurantoin, ampicillin, cephalexin, trimethoprim, sulfamethoxazole, and the combination trimethoprim-sulfamethoxazole. Norfloxacin was more active than the other agents against all gram-negative organisms tested. Minimal inhibitory concentrations (MICs) of Pseudomonas aeruginosa were less than or equal to 0.125-32 mg/l with 90% inhibited (MIC90) by 4 mg/l; MICs of the Enterobacteriaceae including Serratia marcescens were less than or equal to 0.125-8 mg/l with an MIC90 of less than or equal to 4 mg/l. There was also excellent activity against the gram-positive cocci including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus and the enterococci, with MICs less than or equal to 0.125-4 mg/l and an MIC90 less than or equal to 4 mg/l. Only 8 of 477 organisms were norfloxacin-resistant (MIC greater than or equal to 16 mg/l): 3 of 100 Pseudomonas aeruginosa, 3 of 10 Pseudomonas maltophilia and 2 of 15 Streptococcus bovis strains. In contrast, 97% of the gram-positive cocci and 49% of the gram-negative bacilli were nalidixic acid-resistant (MIC greater than or equal to 32 mg/l). Norfloxacin shows excellent activity against a wide range of bacteria and merits further study as a urinary antibacterial agent.

Anti-Bacterial Agents↗

Three to eight weeks of therapy with netilmicin: toxicity in normal and diabetic patients.

Twenty-eight patients, 24 men and 4 women, aged between 17 and 72 years old, and suffering from chronic osteomyelitis (19), mastoiditis (5), or serious wound infections (4) were treated for an average of 35 days with netilmicin at doses of 2.4 to 6.9 mg/kg/day. The total dose of netilmicin given to each patient ranged from 3700 to 23 220 mg. Although the renal function was initially normal in all patients and stayed normal throughout therapy in all patients with no underlying disease, netilmicin nephrotoxicity was detected in two diabetic patients (7.6%). Vestibular toxicity developed in two (7.6%) but no change in audiograms was noted. Long-term therapy was associated with a significant increase (P less than 0.001) in half-life, from 1.5 to 1.9 h, and AUC 7.9 to 13.1 mg/l/h.

Adult↗

Chemoprophylaxis for Neisseria meningitidis in an isolated Arctic community.

Community chemoprophylaxis with a regimen of sequential minocycline/rifampin (adults) or rifampin alone (children [less than 12 years of age]) was undertaken in a remote Arctic community one year after an outbreak of meningitis due to Neisseria meningitidis serogroup B. Nasopharyngeal carriage rates of N. meningitidis before prophylaxis were 32.4% in Inuit (Eskimos) and 6% in Caucasians, with maximal carriage (44.8%) in adolescents. Serogroup B accounted for 63.9% of all isolates before prophylaxis. One week after prophylaxis, the nasopharyngeal carriage rates were 0.8% in Inuit who had received prophylaxis and 33.3% in those who had not received prophylaxis (P less than 0.005). This reduction persisted at nine weeks after prophylaxis, when carriage rates were 1.2% in those who had received prophylaxis and 22.6% in individuals who had not received prophylaxis. Of the strains obtained before prophylaxis, 7.8% were sulfadiazine-resistant, whereas 35% of all isolates obtained from prophylaxis were sulfadiazine-resistant. Rifampin- or minocycline-resistant strains were not identified either before or after prophylaxis.

Adolescent↗

Genital ulcers in Kenya. Clinical and laboratory study.

Of 97 patients with genital ulcers attending a special treatment clinic in Nairobi, Kenya, 60 harboured Haemophilus ducreyi, four herpes simplex virus, and five Neisseria gonorrhoeae. Eleven patients had serological evidence of syphilis; of these one case was confirmed by darkfield microscopy. In the remaining cases no aetiological agent was identified. An enriched chocolate agar with vancomycin and serum was a useful medium for primary isolation of H ducreyi. Tetracycline was generally ineffective in the treatment of ulcers, but sulfadimidine was successful in almost 80% of cases.

Adult↗