Shin Kawai

Tuberculin skin testing in uveitis patients and treatment of presumed intraocular tuberculosis in japan

PURPOSE To evaluate the results of tuberculin skin testing in Japanese patients with intraocular inflammation and to assess the outcome of treatment for presumed intraocular tuberculosis in selected patients. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS One hundred twenty-six patients, newly referred to the Ocular Inflammation Service at the Kyorin Eye Center from April 1998 to August 2000, underwent systemic evaluation for the diagnosis and/or treatment of uveitis. METHODS Tuberculin skin testing with purified protein derivative was performed as part of the systemic evaluation. The diagnosis of presumed intraocular tuberculosis was made when findings were consistent with possible intraocular tuberculosis, the tuberculin skin test was positive (induration more than 10 mm), and no other cause of uveitis was suggested by symptoms, signs, or ancillary testing. Using these criteria, 10 patients were given a diagnosis of presumed intraocular tuberculosis and treated with antituberculosis therapy consisting of isoniazid, with or without rifampicin. Some of these patients also received a tapered course of oral corticosteroids after the initiation of antituberculosis treatment. None of the patients had any signs or symptoms of acquired immunodeficiency syndrome. MAIN OUTCOME MEASURES Visual acuity and ophthalmologic examination to assess degree of intraocular inflammation. RESULTS Twenty-six of the 126 patients (20.6%) had a positive tuberculin skin test result. Ten of these 26 patients (38.5%) were treated for a diagnosis of presumed intraocular tuberculosis. Nine patients had no evidence of pulmonary tuberculosis, and one patient had presumed tuberculous hilar lymphadenitis. The predominant clinical finding was choroidal or optic disc nodule in three patients, retinal vasculitis in three patients, and choroiditis in four patients. Nine patients exhibited decreased intraocular inflammation with treatment. CONCLUSIONS Roughly one fifth of the uveitis patients who underwent systemic evaluation had a positive tuberculin skin test result, and 9 of 10 selected skin test-positive patients with clinical findings consistent with intraocular tuberculosis had a favorable response to antituberculosis therapy. These results suggest that intraocular tuberculosis continues to be a major diagnostic consideration for uveitis patients in Japan.

Animal Model of Mycoplasma pneumoniae Infection Using Germfree Mice

ABSTRACT We have attempted to establish a gnotobiotic mouse model monoassociated with Mycoplasma pneumoniae following single or repeated infection to examine the mechanism of pathogenesis following M. pneumoniae infection. M. pneumoniae inoculated into germfree mice colonized equally well at 105 CFU/lung in both single infection and repeated infection. In histopathological observation, repeatedly infected mice showed pneumonia with mild infiltration of mononuclear cells and macrophages. Antibody titers against M. pneumoniae rose in the repeatedly infected mice but not in the singly infected mice. The percentage of CD4-positive, CD8-positive, and CD25-positive lymphocytes infiltrated in the lung was increased in the repeatedly infected mice. In contrast, the lymphocyte subset in the spleen was not significantly different among mock-, singly, and repeatedly infected mice. In the study of cytokine productivity of spleen cells, production of interleukin (IL)-4 and IL-10 was significantly increased and that of gamma interferon was remarkably increased in the mice following repeated infection. These results indicate that a gnotobiotic mouse model monoassociated with M. pneumoniae was established and that immune mechanisms might be involved in the pathogenesis in pneumonia following M. pneumoniae infection.

Immunological analysis and pathological examination of gnotobiotic mice monoassociated with Mycoplasma pneumoniae

Although mycoplasmal pneumonia has been generally considered to be a disease with good prognosis, a pathogenic host immune response has been associated with its occurrence. In the present study, the pathogenic significance of the immune response was examined using germ-free mice either infected intranasally with Mycoplasma pneumoniae or inoculated with M. pneumoniae antigens (soluble antigen and partially purified antigen). In gnotobiotic mice monoassociated with M. pneumoniae, 10(4) c.f.u. M. pneumoniae per lung were isolated 2-28 days after infection. Inflammatory changes with infiltration of lymphocytes were histopathologically detected in the perivascular area at 2 and 7 days after infection. In the mice intranasally inoculated with soluble antigen or partially purified antigens (F6 and F10 antigens), infiltration of neutrophils and lymphocytes was histopathologically detected at 2 days after inoculation. Severe pneumonia with tissue destruction was observed in the mice inoculated with F6 antigen. A gamma interferon (IFN-gamma) dominant response in endogenous cytokine expression was observed in all the treated mice. These results indicate that inflammatory changes in the lung tissue were prolonged in gnotobiotic mice monoassociated with M. pneumoniae compared with mice inoculated with M. pneumoniae antigen. In addition, it was shown that IFN-gamma plays an important role in the pathogenesis of pneumonia in mice either infected with M. pneumoniae or inoculated with its antigen. In particular, the F6 antigen has been considered to be an important virulence factor in terms of induction of tissue injury causing infiltration of lymphocytes and neutrophils in the lung, suggesting a close interaction between the immune response and the occurrence of M. pneumoniae pneumonia.

The role of interleukin-10 in systemic inflammatory response syndrome with sepsis

This study was performed to demonstrate the role of interleukin (IL)-10, especially in systemic inflammatory response syndrome (SIRS) patients. In clinical observations, levels of serum tumor necrosis factor-α (TNF) and IL-10 increased in SIRS patients (TNF, n=43; IL-10, n=33), and they increased more in the patients with organ failure (n=22) than in patients without organ failure (n=24), (P<0.01). In mice, serum TNF and IL-10 began to increase at 1 hour after injection with 4mg/kg of lipopolysaccharide (LPS) and reached a maximum at 2 hours. However, the serum level of TNF decreased to an undetectable level at 6 hours, while a significant amount of IL-10 remained in serum. The TNF elevation induced by LPS injection was inhibited by pretreatment with 200 ng of IL-10 (P<0.1 in serum,P<0.05 in bronchoalveolar lavage fluid). Neutrophil reduction induced by LPS injection was also inhibited by pretreatment with 1 μg of IL-10. On human neutrophils the expression of adhesion molecules LFA-1 and MAC-1 that resulted from in vitro incubation with TNF were suppressed by the addition of IL-10 supplement. The expression of TNF receptors on the surface of human neutrophils as a result of LPS loading was also suppressed by IL-10 supplement. IL-10 seems have a protective function in the progress to organ failure in SIRS patients with sepsis. IL-10 suppresses TNF production and inhibits the expression of adhesion molecules and TNF receptors on neutrophils.

Toward the rational use of standardized infection ratios to benchmark surgical site infections

BACKGROUND The National Healthcare Safety Network transitioned from surgical site infection (SSI) rates to the standardized infection ratio (SIR) calculated by statistical models that included perioperative factors (surgical approach and surgery duration). Rationally, however, only patient-related variables should be included in the SIR model. METHODS Logistic regression was performed to predict expected SSI rate in 2 models that included or excluded perioperative factors. Observed and expected SSI rates were used to calculate the SIR for each participating hospital. The difference of SIR in each model was then evaluated. RESULTS Surveillance data were collected from a total of 1,530 colon surgery patients and 185 SSIs. C-index in the model with perioperative factors was statistically greater than that in the model including patient-related factors only (0.701 vs 0.621, respectively, P < .001). At one particular hospital, for which the percentage of open surgery was lowest (33.2%), SIR estimates changed considerably from 0.92 (95% confidence interval: 0.84-1.00) for the model with perioperative variables to 0.79 (0.75-0.85) for the model without perioperative variables. In another hospital with a high percentage of open surgery (88.6%), the estimate of SIR was decreased by 12.1% in the model without perioperative variables. CONCLUSION Because surgical approach and duration of surgery each serve as a partial proxy of the operative process or the competence of surgical teams, these factors should not be considered predictive variables.

Psittacosis with increased gammadelta T cells in bronchoalveolar lavage fluid.

Experience with two cases of psittacosis is described here in which the number of gammadelta T cell receptor-positive T lymphocytes (gammadelta T cell) in the bronchoalveolar lavage fluid was markedly increased (25.1 and 66.9%) and CD8+ T cells were also increased with reversal of the CD4/CD8 ratio. These values improved to the normal range along with recovery of their radiographical findings. The present findings suggest that gammadelta T cells may play an important role in protection from lung injury caused by Chlamydia psittaci infection.

Evidence for cytomegalovirus-induced haemophagocytic syndrome in a young patient with AIDS

A 29-year-old man with HIV infection was referred to our department because of a 1-month history of low-grade fever and fatigue. Bone marrow aspiration and biopsy showed findings consistent with haemophagocytic syndrome (HPS), and immunohistochemical assessment showed cytomegalovirus (CMV) infection. HIV-associated HPS can occur at any stages of HIV disease and requires diverse differential diagnosis. CMV-associated HPS (CMV-HPS) in patients with HIV infection is relatively rare, but the present case showed that the clinicians should consider the possibility of CMV-HPS as a clinical feature of CMV infection.

An HIV-infected Patient with Confirmed Overlapping Complications of Severe Amebic Colitis and CMV Enteritis

We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.