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Biomedical subjects

S J Hopkins

Publications and source records attributed to S J Hopkins.

15 recordsLinked to original sources

A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.

BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.

Adolescent

Cytokine inter-relationships and their association with disease activity in arthritis.

In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.

Arthritis

Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients.

Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors.

Acute-Phase Reaction

Interleukin-6 is a centrally acting endogenous pyrogen in the rat.

Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20-100 ng) caused significant increases in colonic temperature and resting oxygen consumption (VO2) in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (alpha-helical CRF9-41, 25 micrograms, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in VO2 and temperature, and very high doses given intravenously (i.v.) (4 micrograms/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1 beta (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and VO2 in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.

Animals

Bioassay of interleukin-1 in serum and plasma following removal of inhibitory activity with polyethylene glycol.

Serum and plasma normally inhibit the responsiveness of the indicator cells used in bioassays for interleukin-1 (IL-1). A precipitation step with 12% polyethylene glycol (PEG) was found to remove material responsible for such inhibition. The IL-1 bioassay could be performed in the presence of a 3% concentration of PEG and recovery of added natural IL-1 from plasma or serum was essentially complete.

Animals

Challenges for continuing education of public health nurses in Florida.

Perceived continuing education needs among public health nurses at the staff and supervisory levels were investigated. A questionnaire was adapted for each and administered at participating county public health units. Results indicated a high level of agreement between staff nurses and supervisors. Further analysis of the data suggested a relationship between the nurses' perception of continuing education needs and the realities of their nursing practice. Public health nurses, educators, and administrators face the challenge of refocusing continuing education needs and activities on the broad scope of this area of specialty.

Adult

Contact hypersensitivity induces plasma interleukin 6.

Previous studies in this laboratory have revealed that elicitation reactions in contact-sensitized mice correlate closely with elevations in the serum concentration of acute-phase proteins. Regulation of the hepatic synthesis of acute-phase proteins is one of the many biological functions ascribed to interleukin 6 (IL-6). We now provide evidence that contact reactions are also associated with a rapid and substantial increase in the plasma concentration of IL-6. Quantitative assessment of plasma IL-6 may provide a useful serological method for the evaluation of experimental allergic contact dermatitis in mice, and possibly in other species.

Animals

Production of interleukin-1 by draining lymph node cells during the induction phase of contact sensitization in mice.

Biologically active interleukin-1 (IL-1) has been detected in supernatants of draining lymph node cells isolated from contact-sensitized mice. Induction of IL-1 was dependent upon the concentration of sensitizer applied and occurred within 2 hr of exposure. The IL-1 activity could not be attributed to other interleukins and was neutralized by a specific antiserum. Reduced concentrations of IL-1 were produced by cells isolated from the draining nodes of mice that had been pre-exposed to the sensitizer. Since IL-1 has the potential to influence several aspects of lymphocyte activation, the production of significant concentrations of biologically active IL-1 by draining lymph node cells indicates that it is likely to play an important role in the afferent phase of contact sensitization.

Animals

Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon.

Cytokine-specific monoclonal antibodies were used in enzyme-linked immunoadsorbant assays (ELISA) to examine a variety of synovial fluids for the presence of cytokines which might be expected to play some part in the pathology of arthritis. Low, but significant, levels of tumour necrosis factor alpha (TNF-alpha) were present in the majority of synovial fluids obtained from rheumatoid arthritis patients with a sero-positive history. Low levels of interferon (IFN)-alpha and IFN-gamma were also detected, but only IFN-alpha was significantly increased in the sero-positive group. Tumour necrosis factor beta (TNF-beta) was present only in trace amounts. These results suggest that the presence of cytokines, such as TNF-alpha and IFN-alpha in synovial fluid may be associated with tissue changes observed in rheumatoid joint disease and thus contribute to the pathology of the arthritis, but support evidence for the minimal role likely to be played by IFN-gamma in the joint pathology of rheumatoid arthritis.

Arthritis

Characterization of the IgG antibody response to timothy grass pollen antigens.

The IgG and IgE antibody responses against timothy grass pollen antigen B (AgB) in several mouse strains were determined. Considerable variability in both responses was demonstrated, and (CBA/J X C57BL/6)F1 mice were selected for use in subsequent experiments. Anti-idiotypic-antibody-induced T suppressor cells almost completely suppressed AgB-specific IgE, but the IgG response was not altered. Further studies with photooxidized AgB (Ox-AgB) indicated that the IgG response was directed against an antigenic determinant expressed on both native antigen and Ox-AgB. Our data indicates that AgB possesses two distinct antigenic determinants, one that induces an IgE response, and one that induces an IgG response.

Animals