Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.     

A five year follow up into changes in caries experience amongst a sample of 12 year old children from Athens

The airway functions in pregnancy have been widely studied but reports obtained from Western and Indian population show divergence. While the Indian populations show significant changes in total and timed vital capacity (FVC and FEV1), the Western counterparts dismiss such changes as insignificant. Our results show insignificant alteration in airway function and support the results reported for Western population.     

Role of arm proprioception in calibrating the arm-eye temporal coordination

When subjects track with the eyes an arm-attached target, eye latency is shorter than when tracking an external target. This improved synchrony could result from either a common command addressed to the two systems or from an influence of the arm command on eye motion initiation. According to the first hypothesis, the eyes should start moving long before the arm, because of the difference in dynamics. We recorded arm and eye motion together with biceps muscle activity in controls and a deafferented subject. Data support the second hypothesis. Moreover, the deafferented subject showed a lesser correlation between arm and eye motions than controls, suggesting a role for arm proprioception in the calibration of the temporal relationship between arm and eye movements.     

Load pattern and pressure pain threshold in the upper trapezius muscle and psychosocial factors in medical secretaries with and without shoulder/neck disorders

OBJECT: A current hypothesis for the genesis of muscular complaints in the shoulder/neck region postulates that short periods with a completely relaxed muscle are essential to avoid complaints. Another hypothesis is that these disorders are related to psychosocial conditions at work. In order to test these hypotheses, 23 medical secretaries were investigated. METHODS: The load pattern during work in the upper trapezius muscle bilaterally was assessed with electromyographic (EMG) technique and exposure variation analysis (EVA). In addition, pressure pain threshold (PPT) was measured on the trapezius muscle bilaterally and on the sternum. Psychosocial conditions at work were assessed with a questionnaire. RESULTS: The medical secretaries with complaints had significantly fewer episodes with totally or close to totally relaxed muscle compared with the healthy group. The group with complaints tended to have a more monotonous load pattern at low levels (approx. 1%-5% maximum voluntary contraction) while the healthy group had more frequent pauses but also somewhat more frequent short load peaks. The group with complaints showed lower PPT readings compared with the healthy group. However, the whole group had considerably lower PPTs than is usually reported in the literature. Of the 12 questions in the psychosocial questionnaire only one regarding work task satisfaction showed a significant difference between the two groups. CONCLUSION: Support is found for hypothesis that secretaries without complaints have more frequent episodes with totally relaxed muscle. A significant difference is found regarding work task satisfaction.     

Population pharmacokinetics of sirolimus in kidney transplant patients

OBJECTIVE: To characterize the dose-related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two-stage and nonlinear mixed-effect model population methods. METHODS: Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady-state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first-order absorption (ka) and a lag-time. RESULTS: The nonlinear mixed-effect model method (P-Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration-independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half-life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag-time of 0.27 hour (35.1%), and ka of 2.77 hr-1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interactions. CONCLUSION: This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.