Trauma, stressful life events and depression predict HIV-related fatigue.

Despite the fact that fatigue is a common and debilitating symptom among HIV-infected persons, we know little about the predictors of fatigue in this population. The goal of this cross-sectional study was to examine the effects of early childhood trauma, recent stressful life events and depression on intensity and impairment of fatigue in HIV, over and above demographic factors and clinical characteristics. We studied 128 HIV-infected men and women from one southern state. The median number of childhood traumatic events was two and participants tended to have at least one moderate recent stressful event. Multiple regression findings showed that patients with less income, more childhood trauma, more recent stressful events and more depressive symptoms had greater fatigue intensity and fatigue-related impairment in daily functioning. Recent stresses were a more powerful predictor of fatigue than childhood trauma. None of the disease-related measures (e.g. CD4, viral load, antiretroviral medication) predicted fatigue. Although stress and trauma have been related to fatigue in other populations, this is the first study to examine the effects of traumatic and recent stressful life events on fatigue in an HIV-infected sample.

Measuring fatigue in people living with HIV/AIDS: psychometric characteristics of the HIV-related fatigue scale.

In the era of life-prolonging antiretroviral therapy, chronic fatigue is one of the most prevalent and disabling symptoms of people living with HIV/AIDS, yet its measurement remains challenging. No instruments have been developed specifically to describe HIV-related fatigue. We assessed the reliability and construct validity of the HIV-Related Fatigue Scale (HRFS), a 56-item self-report instrument developed through formative qualitative research and designed to measure the intensity and consequences of fatigue as well as the circumstances surrounding fatigue in people living with HIV. The HRFS has three main scales, which measure fatigue intensity, the responsiveness of fatigue to circumstances and fatigue-related impairment of functioning. The functioning scale can be further divided into subscales measuring impairment of activities of daily living, impairment of mental functioning and impairment of social functioning. Each scale demonstrated high internal consistency (Cronbach's alpha=0.93, 0.91 and 0.97 for the intensity, responsiveness and functioning scales, respectively). The HRFS scales also demonstrated satisfactory convergent validity when compared to other fatigue measures. HIV-Related Fatigue Scales were moderately correlated with quality of nighttime sleep (rho=0.46, 0.47 and 0.35) but showed only weak correlations with daytime sleepiness (rho=0.20, 0.33 and 0.18). The scales were also moderately correlated with general mental and physical health as measured by the SF-36 Health Survey (rho ranged from 0.30 to 0.68 across the 8 SF-36 subscales with most >0.40). The HRFS is a promising tool to help facilitate research on the prevalence, etiology and consequences of fatigue in people living with HIV.

Characterization of cyclooxygenase-2 (COX-2) during tumorigenesis in human epithelial cancers: evidence for potential clinical utility of COX-2 inhibitors in epithelial cancers.

Increased prostaglandins (PGs) are associated with many inflammatory pathophysiological conditions; and are synthesized from arachidonic acid by either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent epidemiologic, expression, and pharmacologic studies suggest COX-2 derived metabolites also play a functional role in the maintenance of tumor viability, growth and metastasis. Archival and/or prospectively collected human tissues were prepared for immunohistochemistry, and representative cases assayed via Western blot, RT-PCR, or TAQman analysis. Consistent overexpression of COX-2 was observed in a broad range of premalignant, malignant, and metastatic human epithelial cancers. COX-2 was detected in ca. 85% of the hyperproliferating, dysplastic, and neoplastic epithelial cells, and in the existing and angiogenic vasculature within and adjacent to hyperplastic/neoplastic lesions. These data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers.

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

A new method for the adaptive determination of optimum pH and temperature.

An adaptive control algorithm for the on-line determination of optimal temperature or pH for biomass production in a continuous fermentor is presented. The algorithm requires no prior information and uses a dynamic Hammerstein model to identify parameters and to estimate an optimal steady-state control value. A check of the estimated performance measure second derivative is included to ensure that the target extremum is an optimum. The process is driven towards this optimum with a variable step size that depends on the quality of the on-line identified model. Numerical simulations are performed on a dynamic chemostat model that incorporates a metabolic time delay. The algorithm successfully finds the optimum temperature or pH values and maintains the reactor at the optimum steady state.