Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

Congenital rubella in babies of south Asian women in England and Wales: an excess and its causes

The incidence of congenital rubella was found to be 2.3 times higher in Asian than non-Asian births in England and Wales. This was attributed in part to higher susceptibility to rubella in Asian than non-Asian women, as shown by antenatal serological data from public health laboratories in Leeds, Luton, and Manchester. Examination of the ethnic origin of pregnant women requesting laboratory testing after contact with rubella or rash and of women with laboratory confirmed rubella in pregnancy also suggested that the disease was being underdiagnosed in pregnant Asian women. Failure to prevent congenital rubella by termination of infected pregnancies may therefore contribute to the increased incidence of the syndrome in Asians. Health education programmes about the dangers of rubella in pregnancy and of the need for vaccination can readily be promoted in the Asian community through existing ethnic organisations. Protection of other ethnic minorities likely to be at similar increased risk may require a vaccination programme aimed at national elimination of rubella.     

Tacrolimus Pharmacokinetics and Dose Monitoring After Lung Transplantation for Cystic Fibrosis and Other Conditions

In cystic fibrosis (CF), absorption of tacrolimus through the gastrointestinal tract may be impaired due to fat malabsorption. The aim of this pilot study was to compare tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure in stable lung transplant recipients with and without CF, and to determine the best single-time predictors of exposure. The study included 11 lung transplant recipients with CF and 11 without CF who received tacrolimus twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h postdose on 3 separate days within 1 week. Tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure were similar in the two groups, though exposure-per-milligram-dose was approximately 50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC(0-12)), but the concentration measured 3 h postdose (C(3)) was tightly correlated with the AUC(0-12) in both CF (r(2)= 0.86) and non-CF (r(2)= 0.92) patients. In summary, patients with CF have a higher tacrolimus oral clearance, but nonsignificant differences in short-term inter- and intrasubject variability of exposure compared to patients without CF. C(3) is tightly correlated with AUC(0-12) in lung transplant recipients with and without CF.