Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs

PURPOSE: To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. METHODS: After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. RESULTS: Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. CONCLUSION: Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.     

Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.     

Treatment of experimental meconium aspiration syndrome with surfactant lung lavage and conventional vs. asymmetric high-frequency jet ventilation

Respiratory failure caused by meconium aspiration requires combined strategies. We hypothesized that surfactant lung lavage with asymmetric high-frequency jet ventilation (AHFJV) can increase the removal of meconium and improve lung function. During conventional ventilation (CV), a suspension of human meconium (25 mg/ml, 4 ml/kg) was instilled into the tracheal tube of anesthetized rabbits to cause respiratory failure. Animals were then divided into four groups: saline lavage + CV (Sal-CV), surfactant lavage + CV (Surf-CV), saline lavage + HFJV (Sal-HFJV), and surfactant lavage + HFJV (Surf-HFJV). Lung lavage (10 ml/kg in 3 portions) was performed with diluted surfactant (Curosurf, 100 mg of phospholipids/kg) or saline during CV (frequency (f), 30/min; inspiration time (Ti), 50%) or AHFJV (f, 300/min; Ti, 70%). Animals were ventilated for an additional hour with either CV or HFJV (Ti, 50%). Surfactant lavage with both CV and AHFJV removed more meconium than saline lavage. However, the highest removal was found in the Surf-HFJV group vs. all other groups (P < 0.05). The oxygenation index decreased after surfactant lavage in both groups compared to controls (P < 0.001), and more prominently in the Surf-CV group. Elimination of CO(2) was significantly higher in the Surf-HFJV group vs. all other groups (P < 0.05). The ventilation efficiency index increased after lavage in both surfactant groups vs. saline controls (P < 0.05). Dynamic lung-thorax compliance gradually increased, and right-to-left pulmonary shunts decreased in both surfactant groups vs. saline controls after lavage (P < 0.05). Combination of surfactant lavage with both CV and AHFJV was beneficial in rabbits with meconium aspiration syndrome. While AHFJV was more effective in the removal of meconium, CV had a more favorable effect on lung function in the postlavage period.     

Socio-demographic,behavioral and functional characteristics of groups of community and institutionalized elderly Quechua Indians of Peru,and their association with nutritional status

Socio-demographic, behavioral, functional and anthropometric data for groups of elderly Quechua Indians of Peru were used to investigate the effects of gender and lifestyle patterns on nutritional status. Two community-dwelling samples were selected for study, representative of divergent lifestyles in terms of their combination of socio-economic, demographic and cultural contexts, plus an ad-hoc sample of institutionalized individuals with controlled food intake and reduced physical activity. Results suggest that differences in socio-demographic, behavioral and functional characteristics exist between the sexes and across settings (low- vs. highland) and lifestyles (institutionalized vs. community-dwelling; semi-urban vs. rural). These factors are likely to be related to diverging dietary and physical activity patterns, and have considerable effects on the nutritional status of the respondents.     

Undetectable viral load is associated with sexual risk taking in HIV serodiscordant gay couples in Sydney

OBJECTIVE: To determine whether reporting that the HIV-positive partner's viral load is undetectable rather than detectable is associated with unprotected anal intercourse (UAI) in HIV serodiscordant gay couples. METHOD: A cross-sectional study nested within two cohort studies, the Health in Men (HIM) cohort of HIV-negative men, from July 2001 to December 2003 and the Positive Health (PH) cohort of HIV-positive men, from February 2002 to August 2003. The study participants were 119 men in an HIV serodiscordant regular relationship of at least 6 months duration (45 HIV-negative men from HIM, 74 HIV-positive men from PH). The main outcome measure was the occurrence of UAI within the relationship in the previous 6 months. RESULTS: Eighty-two men reported no UAI and 37 reported some UAI. Of couples in which the HIV-positive partner's viral load was reported to be undetectable, 39.4% reported UAI compared with 20.8% of those where viral load was reported to be detectable (P = 0.04). In multivariate analysis, significant predictors of UAI were younger age [odds ratio (OR), 0.94; 95% confidence interval (CI), 0.87-1.00; P = 0.05], greater HIV optimism (OR, 4.98; 95% CI, 1.25-19.8; P = 0.02) and reported undetectable viral load (OR, 2.88; 95% CI, 1.13-7.37; P = 0.03). CONCLUSIONS: Most serodiscordant gay couples do not engage in any UAI. UAI within such relationships is significantly more likely to occur where the HIV-positive partner is reported to have undetectable viral load. UAI in HIV serodiscordant relationships is problematic even if viral load is undetectable because of unknown risk parameters, viral load variability and the possibility of drug-resistant strains of HIV.     

CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy

OBJECTIVE: To evaluate the safety of treatment interruption guided by CD4+ cell count in HIV-infected patients followed up prospectively. METHODS: Patients on highly active antiretroviral therapy with CD4+ cell counts > 500 x 10(6) cells/l discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 x 10(6) cells/l. Any patients who resumed therapy would be eligible to interrupt treatment again once their CD4+ cell count increased above 500 x 10(6) cells/l. RESULTS: Data on 71 HIV infected patients is reported. Their median nadir CD4+ cell count before antiretroviral treatment was 352 x 10(6) cells/l [interquartile range (IQR), 294-445 x 10(6) cells/l]. The median CD4+ cell count at the time of first interruption was 790 x 10(6) cells/l (IQR, 657-1041 x 10(6) cells/l). The median follow-up after starting the first treatment interruption was 28.3 months (IQR, 21.4-37.0 months). During the follow-up 49 patients restarted therapy and 22 patients remain off therapy; 24 patients have interrupted therapy twice, nine patients have interrupted therapy three times and six patients four times. No AIDS-defining illnesses occurred during the follow-up. The median duration of the first interruption was 15 months (IQR, 6-26 months). The overall reduction of time on therapy was 71.1%. The duration of the first interruption and the reduction of time on therapy were related to nadir CD4+ cell count. The patients who resumed HAART rapidly regained CD4+ cells and achieved viral suppression. CONCLUSION: If carefully monitored, treatment interruptions guided by CD4+ cell count in patients with an initially high CD4+ cell counts are clinically safe, decrease exposure to the drugs and do not reduce the efficacy of therapy when this is re-started.     

Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry

BACKGROUND AND OBJECTIVES: In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis. DESIGN AND METHODS: Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes. RESULTS: One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively. INTERPRETATION AND CONCLUSIONS: The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.     

Early postoperative complications following liver transplantation

Liver transplantation is a highly successful treatment for patients with end-stage liver disease and acute liver failure. However, serious postoperative complications can significantly compromise patient survival. Complications can be technical, medical, or immunological in nature. The risk of developing early postoperative complications is associated with the patient's preoperative condition, the quality of the donor liver, the quality of the donor and recipient procedure, initial graft function, and perioperative anaesthesiological and intensive care management. The patient's preoperative condition can include gastrointestinal bleeding, acute renal failure, a requirement for cathecholamines or mechanical ventilation, and prolonged encephalopathy for the most detrimental risk factors for developing early postoperative complications. The necessity for prolonged mechanical ventilation or the requirement for reintubation after transplantation can significantly increase the risk of developing pneumonia, sepsis, and multiple organ dysfunction. A decrease in infectious and other complications can be achieved by early postoperative enteral nutition, including the application of probiotics.     

Usefulness of dipyridamole stress echocardiography for predicting graft patency after coronary artery bypass grafting

Noninvasive techniques often provide controversial results in patients who have coronary artery bypass grafts (CABGs). Vasodilator stress echocardiography allows semi-simultaneous imaging of CABG flow and segmental left ventricular wall motion. To assess the comparative and additive value of regional flow and function for noninvasive evaluation of graft patency status, we evaluated 110 consecutive patients who underwent CABG and who were scheduled for coronary angiography. All patients underwent stress echocardiography with dipyridamole (0.84 mg/kg) and atropine (1 mg), including wall motion analysis by 2-dimensional echocardiography and Doppler evaluation of flow reserve of each CABG. Echocardiographic findings were compared with angiographic data. Four patients had inadequate acoustic windows. The remaining 106 patients had 226 grafts performed. Stress echocardiography showed 67% sensitivity, 91% specificity, and 71% accuracy for identification of 50% to 100% stenosis in the graft or in the recipient coronary vessel. There was a fair agreement with angiography (kappa coefficient 0.60). Identification of impaired coronary bypass flow reserve (i.e., <1.9 for internal mammary grafts and <1.6 for saphenous vein grafts) by Doppler had 91% sensitivity, 88% specificity, and 89% accuracy for graft stenosis. There was good agreement with angiographic findings (kappa 0.77). The combination of the 2 techniques achieved 93% sensitivity, 93% specificity, and 93% accuracy, showing a very good agreement with the patency status of the grafts as evaluated at angiography (kappa 0.85). The combined assessment of wall motion and flow reserve in patients who underwent CABG is feasible and provides an accurate estimate of graft patency status by increasing sensitivity of stress echocardiography and specificity of Doppler flow reserve.