The role of immunosuppression and immune-activation in classic Kaposi's sarcoma.

Immunodeficiency and elevated levels of cytokines have been associated with the development of Kaposi's sarcoma (KS) lesions in patients with AIDS and iatrogenic immunodeficiency. However, their role in classic KS (CKS) is unclear. We measured peripheral blood cell levels, including T-cell subsets, as well as neopterin and beta(2)-microglobulin in 91 HIV-negative Greek patients with histologically confirmed CKS and in 107 controls matched for age and sex. CKS cases had slightly lower leukocyte counts (p = 0.08) and lymphocyte counts (p = 0.02). Although the percentage of CD4 and CD8 T-lymphocytes were not significantly different from controls (p = 0.10 and p = 0.45, respectively), CD4 T-lymphocytes were lower in cases than controls (812 cells/microliter and 1,009 cells/microliter, respectively; p = 0.01); part of this difference resulted from the lower lymphocyte counts (p = 0.07 after adjusting for lymphocyte counts). However, neopterin and beta(2)-microglobulin were both considerably elevated [geometric mean (95% CI): 8.35 (7.27-9.73) nmol/L and 2,904 (2,479-3,401) microgram/L in cases and 5.86 (5.40-6. 35) nmol/L and 2,042 (1,880-2,218) microgram/L in controls, respectively]. We conclude that CKS patients are predominantly characterised by immune activation, although an element of minor immunosupression may also be present.

Determinants of progression of HIV infection in a Greek hemophilia cohort followed for up to 16 years after seroconversion.

Our objectives are to describe the progression of HIV disease and to assess the influence of hemophilia-related variables, age at infection, and antibodies to cytomegalovirus infection (anti-CMV) in a Greek cohort of 158 HIV-1-positive hemophilic men, who received prospective follow-up for up to 16 years after infection. A total of 79 patients had died, representing a cumulative progression rate of 72.4% (95% confidence interval [CI], 56.6-83.3). A significant proportion of the mortality (30%) resulted from conditions not formally related to AIDS, with liver failure and cerebral hemorrhage predominant. At 16 years after seroconversion, 66 patients had developed clinical AIDS, a cumulative progression rate of 58.2% (95% CI, 47.1%-86.3%) whereas 15 years after infection 81.5% (95% CI, 74.2%-87.9%) of the patients had AIDS or a CD4 cell count <200 cells/mm3. Hemophilia-related variables or presence of anti-CMV were not significantly associated with disease progression. Age at infection was a strong prognostic factor for all three endpoints. Appropriate modeling showed a nonlinear age effect, with a steeper increase of relative hazard for patients >40 years of age at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Further investigation is required to elucidate the mechanisms of the age effect and the contribution of HCV coinfection on the disease progression.

PIP: The Greek Hemophilia Cohort Study encompasses 158 HIV-positive men with documented seroconversion dates. The present study estimated the rate of progression to all-cause mortality, clinical AIDS, or advanced immunodeficiency 16 years after seroconversion and evaluated the independent effects of hemophilia-related factors, age at seroconversion, and cytomegalovirus status early in the course of infection. Seroconversion dates extended from September 1980 to December 1985. By 1996, after a median follow-up of 11.6 years, 117 of the 158 men had developed AIDS or had a CD4 cell count of 20 cells/cu. mm, and 79 had died. The estimated cumulative incidence rates of clinical AIDS and death over 16 years since infection were 58.1% and 72%, respectively. 30% of the mortality was due to diseases not formally associated with AIDS (e.g., liver failure and cerebral hemorrhage). A significant association existed between older age at seroconversion and more rapid progression to both AIDS and death, with a particularly steep gradient for patients over 40 years old at seroconversion. The age effect remained significant even after controlling for current CD4 cell count. Increases of 1.32-fold and 1.33-fold in the risks of dying and developing AIDS, respectively, were obtained with every one unit decrease in CD4 cell count on the square root scale. Severity of hemophilia, dosage of clotting factor concentrates, and antibodies to cytomegalovirus were not associated with either AIDS risk or mortality. Further investigations are urged to clarify the mechanisms underlying the age effect observed in this study.

Respiratory muscle strength in hyperthyroidism before and after treatment.

We undertook this study to investigate respiratory muscle strength in relation to thyroid function in 20 thyrotoxic patients and in a group of 20 normal subjects matched for age and sex. Global respiratory muscle strength was assessed by measuring mouth pressure during maximal static inspiratory (PImax) and expiratory (PEmax) efforts. We also measured VC, FVC, and FEV1 as well as thyroid-related hormones (T3, T4, TSH). Measurements were made once in normal subjects and twice in thyrotoxic patients, before and 3 months after medical treatment. Our results showed that both maximal pressures were significantly reduced (p less than 0.0001) before treatment in thyrotoxic patients in relation to the mean values of the normal subjects (p less than 0.0001), and they increased significantly (p less than 0.0003) after treatment. Lung volumes were significantly reduced (p less than 0.0001) before and increased significantly (p less than 0.008) after treatment. The ratio FEV1/FVC did not change. A statistically significant linear relationship was found when PImax of patients with thyrotoxicosis before treatment and of normal subjects were plotted against thyroid hormones (T3, T4) (r = -0.746 and r = -0.745, respectively, p less than 0.001). Similarly, a statistically significant linear relationship was found between PEmax and T3 and T4 (r = -0.837 and r = -0.838, respectively, p less than 0.001). No relationship was found between maximal pressures and TSH. Finally, a significant linear relationship was found between PImax and PEmax (r = 0.872, p less than 0.001). Our results confirm that in thyrotoxicosis respiratory muscle weakness occurs that affects both inspiratory and expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)