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A murine model of intratracheally induced histoplasmosis in immunocompromised B6C3F 1 mice was used to evaluate a new triazole antifungal agent, posaconazole. This compound was previously shown to be comparable to amphotericin B and superior to itraconazole for the treatment of histoplasmosis in immunocompetent mice. The current study used mice that were depleted of T lymphocytes by intraperitoneal injection of anti-CD4 and anti-CD8 monoclonal antibodies beginning 2 days before infection and continuing at 5-day intervals until completion of the study. Groups of B6C3F 1 mice that were depleted of CD4 and CD8 T cells were infected with an inoculum of 10 4 Histoplasma capsulatum yeasts. All mice receiving posaconazole at 1 or 0.1 mg/kg of body weight/day, amphotericin B at 2 mg/kg every other day (qod), or itraconazole at 75 mg/kg/day survived to day 29. Only 60% of mice receiving itraconazole at 10 mg/kg/day and none receiving amphotericin B at 0.2 mg/kg qod survived to that date. Fungal burdens were determined at day 14 of infection, 1 day after discontinuation of therapy. Quantitative colony counts and Histoplasma antigen levels in lung and spleen tissues declined following treatment with amphotericin B at 2 mg/kg qod, posaconazole at 5 and 1 mg/kg/day, and itraconazole at 75 mg/kg/day but not in mice treated with amphotericin B at 0.2 mg/kg qod or itraconazole at 10 mg/kg/day. Posaconazole at 0.1 mg/kg/day reduced fungal colony counts and antigen levels in spleens but not in lungs. This study shows posaconazole activity for the treatment of histoplasmosis in immunosuppressed animals.Histoplasmosis is an important cause of progressive infection in immunocompromised individuals, including those with AIDS. In persons with AIDS, the course of disseminated histoplasmosis often is more severe than and the response to treatment is inferior (23,24) to that in nonimmunocompromised individuals or those with other immunosuppressive disorders (19). Eighty-five percent of cases in patients with AIDS have occurred in those with CD4 cell counts below 200/l (13, 20, 22), suggesting that CD4 cells play an important role in defense against Histoplasma capsulatum. Recent studies confirm the association of CD4 cell reduction with increased risk for disseminated histoplasmosis in persons with human immunodeficiency virus infection; case rates were 4.6 times higher in persons with CD4 cell counts below 150/l than in those with higher counts (18). CD8 cell counts were below 200/l in 35% of cases in AIDS patients enrolled in clinical trials evaluating the treatment of histoplasmosis (L. J. Wheat, unpublished data).We have shown that dual depletion of CD4 and CD8 cells markedly alters the course of experimental histoplasmosis following pulmonary challenge (6; C. Schnizlein-Bick, M. Durkin, P. Connolly, S. Kohler, and J. Wheat, Program Abstr. 34th Annu. Meet. Infect. Dis. Soc. Am., abstr. 207, p. 74, 1996). While nonimmunosuppressed mice recovered uneventfully following intratracheal inoculation with 10 3 yeasts, CD4-and CD8-depleted m...

Aims To determine the prevalence of pain and its association with glycaemic control, mental health and physical functioning in patients with diabetes.Methods Cross-sectional data from a multi-site, prospective cohort study of 11 689 participants with diabetes. We analysed the associations of pain severity and interference with glycated haemoglobin (HbA 1c ) measurements and Medical Outcomes Study SF-Mental and Physical Component Summary-12 (MCS-12 and PCS-12) scores.Results Of participants, 57.8% reported moderate to extreme pain and, compared with those without pain, were somewhat older (60.8 vs. 59.9 years, P < 0.001), more obese (body mass index of 32.1 vs. 29.8 kg ⁄ m 2 , P < 0.001), more likely to report being depressed or anxious (41.3 vs. 16.2%, P < 0.001) and more likely to report fair or poor health (48.5 vs. 23.1%, P < 0.001). Bivariate comparisons demonstrated that patients with extreme pain had higher HbA 1c than those without pain (8.3 vs. 8.0%, P = 0.001). In multivariable analyses, pain was not associated with HbA 1c (P = 0.304) but was strongly associated with worse MCS-12 (P < 0.001), PCS-12 (P < 0.001) and depression (P < 0.001). Depression was 1.3 (95% CI: 1.12, 1.96) times more likely in patients with moderate pain and 2.0 (95% CI: 1.56, 2.46) times more likely in patients with extreme pain.Conclusions Moderate to extreme pain was present in 57.8% of diabetic patients. Pain was strongly associated with poorer mental health and physical functioning, but not worse glycaemic control. Recognizing the high prevalence of pain and its strong association with poorer health-related quality of life may be important to improve the comprehensive management of diabetes.Diabet. Med. 27, 578-584 (2010)

Summary Background Research on self-care for chronic disease has not examined time requirements. TRIAD, a multi-site study of managed care patients with diabetes, is among the first to assess self-care time. Objective To examine associations between socioeconomic position and extra time patients spend on foot care, shopping/cooking, and exercise due to diabetes. Data 11,927 patient surveys from 2000–01. Methods Bayesian two-part models were used to estimate associations of self-reported extra time spent on self-care with race/ethnicity, education, and income, controlling for demographic and clinical characteristics. Results Proportions of patients spending no extra time on foot care, shopping/cooking and exercise were respectively 37%, 52% and 31%. Extra time spent on foot care and shopping/cooking was greater among racial/ethnic minorities, less-educated and lower-income patients. For example, African-Americans were about 10 percentage points more likely to report spending extra time on foot care than whites and extra time spent was about three more minutes/day. Discussion Extra time spent on self-care was greater for socioeconomically disadvantaged patients than for advantaged patients, perhaps because their perceived opportunity cost of time is lower or they cannot afford substitutes. Our findings suggest that poorly controlled diabetes risk factors among disadvantaged populations may not be attributable to self-care practices.

The Histoplasma antigen immunoassay utilizes an antibody sandwich method that provides a rapid and reliable means of diagnosing the more severe forms of histoplasmosis. Inhibition assays have been developed for antigen detection and offer at least one potential advantage, namely, reduced antibody requirements. We have developed an inhibition assay using the polyclonal antibody employed in our standard sandwich assay. Urine and serum specimens from patients with culture-proven histoplasmosis and controls were tested using both methods. The two methods had similar sensitivities for detection of antigen in urine (antibody sandwich = 92.5% versus inhibition = 87.5%, P = 0.500) and serum (82.5% versus 80.0%, P = 1.000). With serum, the specificities of both methods were similar (antibody sandwich assay = 95.0% versus inhibition assay = 92.5%,P = 1.000), and with urine, the specificity of the antibody sandwich method was superior (97.5% versus 80.0%,P = 0.039). While the overall reproducibility of both methods was excellent (with urine, antibody sandwich assay intraclass correlation coefficient = 0.9975 and with serum = 0.9949; correlation coefficient of the inhibition assay with urine = 0.9736 and with serum = 0.9850), that of the inhibition method was only fair to poor for the controls: urine = −0.0152, serum = 0.5595. Reproducibility was good for the controls using the sandwich method: urine = 0.7717, serum = 0.9470. Cross-reactivity was observed in specimens from patients infected with Blastomyces dermatitidis,Paracoccidioides brasiliensis, and Penicillium marneffei. In conclusion, the decreased specificity and inferior reproducibility with control specimens suggest that the inhibition assay has poorer precision toward the lower end of the detection range.