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Biomedical subjects

R D Inman

Publications and source records attributed to R D Inman.

At least 19 recordsLinked to original sources
PubMed2003

Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis.

OBJECTIVE: Using humoral immune responses, Klebsiella pneumoniae has been implicated as a candidate microbial trigger in ankylosing spondylitis (AS) by several investigators but refuted by others. The objective of this case-control study was to compare the cellular (T-cell proliferation) and humoral (IgG and IgA, by ELISA) immune responses of affected individuals in multiplex AS families with those of unaffected family members and normal healthy controls in order to find out whether affected individuals exhibit a predominant immune response to K. pneumoniae. METHODS: Twenty-five families with two or more individuals affected with AS and 34 normal healthy controls matched with the affected family members for age, sex and ethnicity were enrolled in the study. All affected (n = 57) and unaffected (n = 37) family members had a detailed clinical evaluation. Peripheral blood was drawn to determine T-lymphocyte proliferation and the IgG and IgA (by ELISA analysis) immune responses to K. pneumoniae, Salmonella typhimurium, Yersinia enterocolitica and Chlamydia trachomatis. Immune responses to each of the four candidate organisms were compared in affected and unaffected individuals. Each individual was classified by the predominant antigenic immune response that they showed when comparison was made among the same concentrations of the four candidate microbial antigens. This stratification was then used (i) to compare immune responses in affected and unaffected family members and (ii) to compare clinical characteristics of affected family members. RESULTS: There was no difference in mean stimulation indices or antibody responses between affected and unaffected family members for each of the candidate organisms. In terms of predominant cellular immune responses to these organisms, there was no difference between affected and unaffected family members with respect to K. pneumoniae, C. trachomatis or Y. enterocolitica. However, a higher percentage of affected family members (25.9%) exhibited a predominant response to S. typhimurium compared with unaffected family members (5.9%, P < 0.02). In assessing antibody titres, K. pneumoniae was the predominant amongst these four organisms, but there was no difference between affected family members, unaffected family members and normal healthy controls. There was no relationship between immune responses and clinical characteristics. CONCLUSION: Our analysis of affected and unaffected family members in familial AS demonstrated no significant differences with respect to cellular or humoral immune responses to K. pneumoniae and three control microbes. In addition, K. pneumoniae did not exhibit a predominant immune response in affected individuals. Thus we find no supportive evidence to implicate a causal role for K. pneumoniae in familial AS.

Adult↗
PubMed2002

Validation of the ethanol breath test and on-table weighing to measure irrigating fluid absorption during transurethral prostatectomy.

OBJECTIVE: To determine the agreement between on-table weighing and the ethanol breath test in measuring the fluid absorption of patients during transurethral prostatectomy (TURP), and to assess the practicality of on-table weighing in the clinical setting. PATIENTS AND METHODS: The absorption of irrigating fluid by the patient during TURP can lead to adverse sequelae, including cardiac stress. Despite modern techniques irrigant may still be absorbed and therefore methods to detect absorption are important. Most methods are impractical or inaccurate, but the expired ethanol technique and continuous on-table weighing are more promising. TURP was undertaken in 44 men (mean age 71 years) using continuous flow 1.5% glycine/1% ethanol as the irrigating solution. Intraoperative irrigant absorption was calculated by the ethanol breath test, using published formulae. Absorption measured by the weighing machine was calculated as (weight gain + blood loss - fluid given), and blood loss by the Hemocue method. RESULTS: The mean (sd) resected weight was 23 (14) g at a mean resection rate of 0.74 g/min. The mean (range) absorption using the balance was 456 (- 343 to 2486) mL, and using the ethanol breath test was 435 (44-2750) mL, with the mean of the differences being - 17 mL, with a 95% confidence interval (CI) of - 81 to -40, the 95% limits of agreement being - 389 to 356 mL (95% CI - 458 to - 337 and 297 to 418 mL). CONCLUSIONS: Both methods are comparable and measure irrigating fluid absorption to levels of accuracy that are useful clinically. Either method could (and should) be used in routine practice.

Absorption↗
PubMed2001

The effect of an anti-HLA-B27 immune response on CTL recognition of Chlamydia.

The interplay between triggering bacteria and HLA-B27 in the pathogenesis of the spondyloarthropathies remains one of the most active areas of investigation in the rheumatic diseases. This has proved difficult to study systematically in the clinical setting, and in this study we utilized a rat model to address the influence that B27-related immunity may have on the process of generating anti-Chlamydia immunity. When splenocytes from HLA-B27 DNA-immunized Lewis (LEW) animals received restimulation in vitro with Chlamydia-treated cells from B27-transgenic LEW rats, we observed that in addition to the expected CTL recognition of HLA-B27, there was also anti-Chlamydia CTL killing of Chlamydia-sensitized syngeneic fibroblast targets. This was not seen when responding cells in vitro were naive LEW splenocytes. To confirm the existence of CTLs recognizing both HLA-B27 and Chlamydia, LEW rats were immunized with B27-transgenic LEW cells, instead of the B27 DNA construct. Splenocytes from the immune rats were restimulated in vitro with Chlamydia-treated B27-transgenic LEW cells. In this instance, the CTLs retained the allele-specific recognition of HLA-B27, as well as recognition of Chlamydia-sensitized syngeneic fibroblasts. Thus, if there is prior expansion of an immune response against HLA-B27, then the resulting splenocytes demonstrate a reduced threshold for generating a primary anti-Chlamydia CTL response. These studies implicate a dynamic interrelationship between recognition of HLA-B27 and Chlamydia trachomatis. The results may have implications for deciphering the cellular basis of Chlamydia-induced reactive arthritis.

Animals↗
PubMed2001

Use of glyceryl trinitrate patches in patients with ureteral stones: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: To report a randomized, double-blind, placebo-controlled trial of glyceryl trinitrate (GTN) patches. The primary outcome measure was stone passage at 6 weeks. GTN is a potent smooth muscle relaxant that may offer benefit by both reducing pain and facilitating ureteral stone passage. METHODS: Fifty consecutive patients, with a single radiopaque calculus less than 10 mm, were randomized to receive a 6-week course of patches containing either 5 mg GTN or placebo. Patients used a diary to record pain episodes during the 6-week study period and were reviewed weekly with x-ray imaging. Analysis was by intention to treat. RESULTS: Twenty-six patients were randomized to the GTN group and 24 to the placebo group. Seven patients in the GTN group discontinued therapy because of headaches. One patient in the placebo group discontinued because of a skin reaction to the patches. No serious adverse events were recorded. No difference was observed in the stone-free rate at 6 weeks (18 patients in each group), interval to stone passage (median GTN 11.5 days versus placebo 13 days), or interventions performed (5 patients each). Although the GTN group reported fewer pain episodes (median 3.5 versus 6.0), this did not achieve statistical significance. CONCLUSIONS: Our preliminary results did not demonstrate a significant advantage in using GTN compared with placebo, with regard to the stone-free rate at 6 weeks, interval to stone passage, or number of episodes of pain experienced.

Administration, Cutaneous↗
PubMed2001

Infectious agents in chronic rheumatic diseases.

The possible role of infectious microorganisms in the disease process of both arthritis and autoimmunity continue to attract both basic and clinical researchers. However, proving a causal role for these suspects is a very difficult and complicated task. This article provides an update on various mechanisms in which microbes may play roles as inciting or perpetuating factors in the pathogenesis of connective tissue disease. It also focuses on current theories that specific microorganisms may play a role in rheumatoid arthritis and ankylosing spondylitis.

Antigens, Bacterial↗
PubMed2001

A comparison of 1.5% glycine and 2.7% sorbitol-0.5% mannitol irrigants during transurethral prostate resection.

PURPOSE: We performed a prospective randomized trial comparing glycine 1.5% with 2.7% sorbitol-0.5% mannitol irrigating solution. We evaluated blood loss, fluid absorption, temperature change, cardiac effects and postoperative symptoms. MATERIALS AND METHODS: Between April 1998 and July 1999, 205 treated patients were included in the statistical analysis. Intraoperative irrigating fluid absorption was measured with the patient on the operating table. Serum cardiac troponin I was used as a marker of perioperative myocardial damage. Operative details were recorded, including the type of anesthesia, resection time and the weight of resected tissue. Postoperative symptoms were documented prospectively. RESULTS: Mean patient age was not significantly different in the glycine and sorbitol-mannitol groups. (72.1 versus 73.7 years). American Society of Anesthesiologists grade was also comparable. Median resection time was 27 minutes and resected tissue weighed a mean of 21 gm. The median resection rate was 0.8 gm. per minute. Blood loss and temperature changes during resection were similar in the 2 groups. Overall median blood loss was 216 ml. and irrigant absorption was 140 ml. In the sorbitol-mannitol group significantly less fluid was apparently absorbed during resection (median 88.2 versus 184.4 ml.). Analysis of the incidence of symptoms of the transurethral prostate resection syndrome did not show any differences in the irrigant groups. Cardiac damage measured using troponin I also showed no significant difference in the 2 groups, although there was a high overall incidence of 7.5%. CONCLUSIONS: We noted no significant differences in 1.5% glycine and 2.7% sorbitol-0.5% mannitol as an irrigating solution for transurethral prostate resection.

Aged↗
PubMed2000

Chlamydia and associated arthritis.

An inflammatory arthritis is known to follow urogenital infection with the intracellular bacterium Chlamydia trachomatis in some individuals, and recent research results have elucidated important aspects of the characteristics of this Chlamydia-associated joint disease. Although the several extra-articular features of Chlamydia-induced arthritis have been defined clinically, their detailed causes remain largely unexplained. Current data indicate that the clinical characteristics of joint disease associated with C. trachomatis infection and those associated with postenteric arthritis are not easily distinguishable, although the response of each to antibiotic therapy does differ. The biologic characteristics of Chlamydia and enteric organisms in the joint show profound differences, and these are probably responsible for the variable responses to drug treatment. Molecular analyses of synovial C. trachomatis have demonstrated that long-term infection of the joint occurs primarily in synovial tissue and that the organism exhibits highly unusual biologic properties in its synovial context. These unusual molecular, biochemical, and other characteristics provide explanations for the frequent culture negativity of joint materials for C. trachomatis and for several other aspects of the arthritogenic process. Much remains to be learned concerning the behavior of this organism in the joint and concerning its interaction with its synovial host cells.

Anti-Bacterial Agents↗
PubMed2000

Tumor necrosis factor receptor p55-deficient mice respond to acute Yersinia enterocolitica infection with less apoptosis and more effective host resistance.

Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55(-/-)). Unexpectedly, TNFRp55(-/-) mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4(+)-T-cell population of splenocytes, whereas TNFRp55(-/-) mice were spared these changes. The splenocytes from TNFRp55(-/-) mice also maintained a robust gamma interferon IFN-gamma response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55(-/-) mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.

Acute Disease↗
PubMed1999

Tumor necrosis factor receptor p55 controls the severity of arthritis in experimental Yersinia enterocolitica infection.

OBJECTIVE: To dissect the host defense mechanisms in relation to the development of Yersinia-associated arthritis by evaluating the impact of tumor necrosis factor receptor p55 (TNFRp55) deficiency on Yersinia enterocolitica infection. METHODS: TNFRp55-/- and C57BL/6 mice were inoculated intravenously with arthritogenic strain 8081 of Yenterocolitica serotype 0:8. Mice were observed daily for generating survival curves and monitoring arthritis. In subsequent sets of experiments, mice were sacrificed at day 14 after infection for examination of histopathology of joints, bacterial clearance, macrophage microbicidal activity, nitric oxide (NO) production, oxidative burst generation, and cytokine production. RESULTS: There was an 80% mortality rate in TNFRp55-/- mice compared with 25% in the controls at 8 weeks after inoculation with 70 colony-forming units of Y. enterocolitica 0:8. Histologic examination of joint tissues revealed that TNFRp55-/- mice developed more severe arthritis, including cartilage degradation and bony destruction, than controls at day 14 after infection. The more extensive joint pathology in TNFRp55-/- mice was correlated with the higher bacterial load in liver, spleen, and lungs, and with the increased levels of interleukin-10. TNFRp55-/- mice displayed impaired intracellular killing of bacteria by macrophages. This was associated with decreased NO production and impaired oxidative burst activity. CONCLUSION: This study demonstrates that TNF signaling through TNFRp55 controls the severity of Yersinia-induced arthritis and implicates TNF-mediated macrophage microbicidal activity as a central event in this process.

Animals↗
PubMed1998

Synoviocyte-packaged Chlamydia trachomatis induces a chronic aseptic arthritis.

The basic mechanisms underlying reactive arthritis and specifically the joint injury that follows intra-articular Chlamydia trachomatis infection have not been defined. The present study addresses this question through the development of an experimental model. Stable cell lines were generated from synoviocytes harvested from the knee joints of Lewis rats. The synoviocytes were cocultivated with C. trachomatis to allow invasion by the microbe and were then transferred by intra-articular injection into the knee joints of Lewis rats. The ensuing arthritis could be subdivided into an early phase (</= 14 d) and a late phase. The early phase was characterized by intense, primarily neutrophilic, synovitis; accelerated cartilage injury; dissemination of Chlamydia to liver and spleen; and viable Chlamydia in the joints. The late phase was marked by mixed mononuclear lymphocyte infiltration in the joint; dysplastic cartilage injury and repair; absence of viable organisms; and development of a distinctive humoral response. Western blot analysis comparing reactive arthritis patients to the experimental model indicates that candidate arthritogenic chlamydial antigens are comparable between the two. This model demonstrates that an intense synovitis can be induced by this intracellular pathogen, and that chronic inflammation can persist well beyond the culture-positive phase. Furthermore, these data show that the synoviocyte is a suitable host cell for C. trachomatis and can function as a reservoir of microbial antigens sufficient to perpetuate joint injury.

Animals↗