Six is enough? Comparison of diffusion parameters measured using six or more diffusion‐encoding gradient directions with deterministic tractography

Diffusion tensor imaging tractography is commonly used to quantify white matter tracts in the human brain via parameters such as fractional anisotropy and mean diffusivity. Simulation studies recommend the use of more than six directions for robust parameter estimates; however, no study has examined the impact of the number of gradient directions on deterministic tractography-derived diffusion parameters in human brain. Here, for 10 major white matter tracts in 11 healthy volunteers at 1.5 T, six-direction diffusion tensor imaging data were compared to 30- or 60-direction data, keeping scan time and number of b = 0 images constant within each test. Mean diffusivity was systematically lower for six-direction protocols (20/40 comparisons); six-direction data had higher fractional anisotropy in the superior longitudinal fasciculus and smaller tract volume for the genu of the corpus callosum. In general, parameter differences due to the number of directions were smaller than those from intersubject variation or signal-to-noise ratio. Despite some absolute differences, standard deviations were significantly different for only one of 160 comparisons. Thus, six-direction data provide diffusion measures with comparable robustness to 30- or 60-direction data and yield appropriate parameter values for most white matter tracts, although there are clear advantages in acquiring higher angular resolution data.     

Focused clinical campaign improves mineral and bone disorder outcomes

As with other disease states, mineral and bone disorder (MBD) management is challenging and may benefit from more systematic management. To evaluate the effectiveness of a focused campaign to improve MBD outcomes, we compared the percentage of patients meeting 2003 Kidney Dialysis Outcomes Quality Initiative (KDOQI)-recommended MBD targets between baseline and 18 months after programme initiation. The four components of the clinical campaign were: (1) a set of grids allowing simultaneous evaluation of MBD test results, (2) a weighted, facility-level cumulative scoring system representing percent of patients within KDOQI-recommended MBD targets, (3) team involvement and (4) patient education. Eighteen months after programme initiation, the percent of patients simultaneously meeting all 2003 KDOQI targets increased 7% and the percent meeting calcium and phosphorus targets increased 24% and 8%, respectively. These findings suggest that a coordinated clinical campaign with effective tools, outcome tracking and sharing and team involvement is an effective strategy to improve MBD outcomes.     

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.     

Intervening sequences in an Archaea DNA polymerase gene.

The DNA polymerase gene from the Archaea Thermococcus litoralis has been cloned and expressed in Escherichia coli. It is split by two intervening sequences (IVSs) that form one continuous open reading frame with the three polymerase exons. To our knowledge, neither IVS is similar to previously described introns. However, the deduced amino acid sequences of both IVSs are similar to open reading frames present in mobile group I introns. The second IVS (IVS2) encodes an endonuclease, I-Tli I, that cleaves at the exon 2-exon 3 junction after IVS2 has been deleted. IVS2 self-splices in E. coli to yield active polymerase, but processing is abolished if the IVS2 reading frame is disrupted. Silent changes in the DNA sequence at the exon 2-IVS2 junction that maintain the original protein sequence do not inhibit splicing. These data suggest that protein rather than mRNA splicing may be responsible for production of the mature polymerase.     

Short (35-cm) versus long (60-cm) flexible sigmoidoscopy: a comparison of findings and tolerance in asymptomatic patients screened for colorectal neoplasia

The purpose of this study was to compare the utility of the 35-cm versus the 60-cm flexible sigmoidoscope in screening asymptomatic patients for colorectal neoplasia. Two hundred fifty-eight patients 45 years of age or older were examined in a randomized fashion with both the 35-cm and 60-cm instruments. Fifteen percent (39/258) of patients had a total of 50 polypoid lesions 3 mm or greater in diameter (including one carcinoma). Of all polypoid lesions, 76% were detected with the 35-cm instrument compared to 98% with the 60-cm sigmoidoscope. Eighty-four percent of all polyps occurred within the distal 35 cm of colon. The mean time required to complete the examination was significantly less with the 35-cm sigmoidoscope than with the 60-cm sigmoidoscope (2.5 vs. 5.7 min). Moderate to severe discomfort was experienced by 69% of patients with the 60-cm instrument compared to only 29% with the 35-cm sigmoidoscope. Seventy-two percent of patients preferred examination with the shorter instrument compared with 7% for the longer sigmoidoscope, while 21% of patients expressed no preference. The 35-cm flexible sigmoidoscope fulfills many criteria of an effective screening test for colorectal neoplasia including rapidity of examination, safety, good sensitivity, and excellent patient acceptance.     

Plasma miR‐122 and miR‐200 family are prognostic markers in colorectal cancer

Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I‐IV disease from a population‐based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non‐metastatic and metastatic colon cancer patients, each group consisting of ten patients with ‘good’ and ten patients with ‘bad’ prognosis were screened. Identified candidate miRNAs were further validated by RT‐qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni‐ and multivariate logistic regression and Cox proportional hazards regression models. Increased miR‐122 levels were associated with a ‘bad’ prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038‐2.347) and a shorter relapse‐free survival and overall survival for non‐metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028‐1.825; HR: 1.353, 95% CI: 1.002‐1.828) and metastatic (HR: 1.264, 95% CI: 1.050‐1.520; HR: 1.292, 95% CI: 1.078‐1.548) CRC patients. Additionally, several members of the miR‐200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR‐122 and the miR‐200 family members, could be of use in the development of a multi‐marker blood test for CRC prognosis.     

Real‐time RF pulse adjustment for B0 drift correction

Although the magnetic field of an MR scanner is very stable under little or no load, it can become less stable under heavy‐duty cycle conditions, such as in diffusion tensor imaging (DTI). Uncorrected, such field drifts lead to an apparent image shift along the phase‐encoding direction and decreasing effectiveness of fat saturation pulses. A method is presented to adjust the center frequency of all RF pulses and the receiver in real time during the acquisition. No data postprocessing or changes to the sequence timing are necessary. In vivo acquisitions were performed to assess the prolonged effectiveness of fat saturation. Field drifts of approximately 2.5 Hz/min were measured and corrected during DTI acquisitions at b‐values of up to 3000 s/mm². The effectiveness of fat saturation diminished over the duration of an 18‐min acquisition when the drift was left uncorrected. The proposed method corrects for apparent image shift and ensures continuously effective fat saturation over the duration of an acquisition. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.