Effect of atorvastatin on cyclosporine pharmacokinetics in liver transplant recipients

BACKGROUND: The development of hyperlipidemia after liver transplant is frequently treated with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) such as atorvastatin. As atorvastatin and the primary immunosuppressant drug, cyclosporine, are metabolized by the same pathway, there is the potential for an interaction. OBJECTIVE: To determine the effect of atorvastatin on cyclosporine pharmacokinetics in liver transplant recipients. METHODS: Six stable, long-term adult liver transplant recipients from a single center who developed posttransplant dyslipidemia were recruited to participate in a 14-day, open-label study of atorvastatin 10 mg/d coadministered with standard posttransplant immunosuppression using constant oral doses-of cyclosporine and corticosteroids. A 10-point pharmacokinetic profile was performed prior to and on day 14 after commencement of atorvastatin therapy. Cyclosporine concentrations were measured by HPLC-electrospray-tandem mass spectrometry. The AUC was calculated by the linear trapezoidal rule, with other parameters determined by visual inspection. RESULTS: Atorvastatin coadministration increased the cyclosporine AUC by 9% (range 0-20.6%; 3018 vs 3290 ng(.)h/mL; p = 0.04). No significant change was evident for other cyclosporine pharmacokinetic parameters. Total cholesterol and low-density lipoprotein cholesterol levels were significantly lower on day 14 than at baseline (p < 0.02). One patient developed a twofold increase in transaminases after 2 weeks of atorvastatin therapy, but no other clinical or biochemical adverse events were recorded. CONCLUSIONS: Atorvastatin coadministration increases the cyclosporine AUC by approximately 10% in stable liver transplant recipients. This change in systemic exposure to cyclosporine is of questionable clinical significance. Atorvastatin is effective in reducing cholesterol levels in liver transplant recipients.

Protein contamination of the laryngeal mask airway and its relationship to re-use

The Laryngeal Mask Airway is a reusable device for maintaining the patency of a patient's airway during general anaesthesia. The device can be reused after it has been cleaned and sterilized. Protein contamination of medical instruments is a concern and has been found to occur despite standard sterilization techniques. The reason for the concern relates to the possibility of the transmission of prions and the risk of developing a neurodegenerative disorder such as Creutzveldt-Jacob disease. The purpose of this study was to quantify the amount of protein contamination that occurs, and to relate this to the number of times the Laryngeal Mask Airway has been used. Fifty previously used Classic Laryngeal Masks were collected after routine sterilization and packaging. The devices were immersed in protein detecting stain and then visual inspection performed to assess the degree and distribution of the staining. The researcher was blinded to the number of times the Laryngeal Mask Airway had been used. Linear regression analysis of the degrees of staining of the airway revealed that protein contamination occurs after the first use of the device and this increases with each subsequent use. This finding highlights the concern that the currently used cleaning and sterilization methods do not prevent the accumulation of proteinaceous material on Laryngeal Mask Airways. Consideration should be given to the search for more efficient cleaning and sterilization techniques or the use of disposable devices.

Cervical Cancer Control, Priorities and New Directions

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.

Uroscopic rainbow: modern matula medicine

Visual inspection of a patient's urine has long been used by physicians, with colour recognised as having important clinical implications. In this review the authors will revisit this ancient pastime with relevance to contemporary medical practice.

A genetic investigation of the covariation among Inspection Time, Choice Reaction Time, and IQ subtest scores

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.

The effect of auditory and visual distracters on the useful field of view: Implications for the driving task

PURPOSE. The driving environment is becoming increasingly complex, including both visual and auditory distractions within the in- vehicle and external driving environments. This study was designed to investigate the effect of visual and auditory distractions on a performance measure that has been shown to be related to driving safety, the useful field of view. METHODS. A laboratory study recorded the useful field of view in 28 young visually normal adults (mean 22.6 +/- 2.2 years). The useful field of view was measured in the presence and absence of visual distracters (of the same angular subtense as the target) and with three levels of auditory distraction (none, listening only, listening and responding). RESULTS. Central errors increased significantly (P < 0.05) in the presence of auditory but not visual distracters, while peripheral errors increased in the presence of both visual and auditory distracters. Peripheral errors increased with eccentricity and were greatest in the inferior region in the presence of distracters. CONCLUSIONS. Visual and auditory distracters reduce the extent of the useful field of view, and these effects are exacerbated in inferior and peripheral locations. This result has significant ramifications for road safety in an increasingly complex in-vehicle and driving environment.

Determinants of visual 2-D echo assessment of left ventricular wall motion: Comparison with myocardial thickening on cardiac magnetic resonance imaging

Background: left ventricular wall motion on 2d echo (2de) is usually scored visually. we sought to examine the determinants of visually assessed wall motion scoring on 2de by comparison with myocardial thickening quantified on MRI. Methods: using a 16 segment model, we studied 287 segments in 30 patients aged 61+/ -11 years (6 female), with ischaemic LV dysfunction (defined by at least 2 segments dysfunctional on 2de). 2de was performed in 5 views and wall motion scores (WMS) assigned: 1 (normal) 103 segments, 2 (hypokinetic) 93 segments, 3 (akinetic) 87 segments. MRI was used to measure end systolic wall thickness (ESWT), end diastolic wall thickness (EDWT) and percentage systolic wall thickening (SWT%) in the plane of the 2de and to assess WMS in the same planes visually. No patient had a clinical ischemic event between the tests. Results: visual assessment of wall motion by 2de and MRI showed moderate agreement (kappa = 0.425). Resting 2de wall motion correlated significantly (p

Indexing text and visual features for WWW images

In this paper, we present a novel indexing technique called Multi-scale Similarity Indexing (MSI) to index imagersquos multi-features into a single one-dimensional structure. Both for text and visual feature spaces, the similarity between a point and a local partitionrsquos center in individual space is used as the indexing key, where similarity values in different features are distinguished by different scale. Then a single indexing tree can be built on these keys. Based on the property that relevant images haves similar similarity values from the center of the same local partition in any feature space, certain number of irrelevant images can be fast pruned based on the triangle inequity on indexing keys. To remove the ldquodimensionality curserdquo existing in high dimensional structure, we propose a new technique called Local Bit Stream (LBS). LBS transforms imagersquos text and visual feature representations into simple, uniform and effective bit stream (BS) representations based on local partitionrsquos center. Such BS representations are small in size and fast for comparison since only bit operation are involved. By comparing common bits existing in two BSs, most of irrelevant images can be immediately filtered. Our extensive experiment showed that single one-dimensional index on multi-features improves multi-indices on multi-features greatly. Our LBS method outperforms sequential scan on high dimensional space by an order of magnitude.