What is the meaning of colorectal transit time measurement?

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P < 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P < 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P <0.001). This may explain why a large percentage of constipated patients have been found by most authors to have normal colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.     

Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure

Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)     

TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype

Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Ulnar-Mammary syndrome (UMS) is a distinct rare, autosomal dominant condition caused by mutations in the TBX3 gene. TBX5 and TBX3 are physically linked in cis on human chromosome 12 and contiguous chromosome 12q24 deletions comprising both TBX5 and TBX3 genes have been previously reported but to our knowledge, duplications have never been described. We report on a large German family with at least 17 affected individuals over 6 generations bearing a duplication at 12q24.21 identified on array-CGH comprising both TBX5 and TBX3 genes. Affected patients are presenting with HOS and UMS symptoms, consisting of variable limb anomalies involving the radial and the ulnar rays and cardiac findings such as congenital heart defects, persistent arterial duct or aortic stenosis, and non-classical symptoms, such as supernumerary nipples and cardiomyopathy. Fluorescence in situ hybridisation confirmed a tandem duplication at the 12q24.21 locus. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype.     

Quality of life after high-dose-rate brachytherapy monotherapy for prostate cancer

Purpose

There is little information in the literature on health-related quality of life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy monotherapy for prostate cancer.

Materials and Methods

We conducted a prospective study of HRQOL changes due to HDR brachytherapy monotherapy for low risk or favorable intermediate risk prostate cancer. Sixty-four of 84 (76%) patients who were treated between February 2011 and April 2013 completed 50 questions comprising the Expanded Prostate Cancer Index Composite (EPIC) before treatment and 6 and/or 12 months after treatment.

Results

Six months after treatment, there was a significant decrease (p<0.05) in EPIC urinary, bowel, and sexual scores, including urinary overall, urinary function, urinary bother, urinary irritative, bowel overall, bowel bother, sexual overall, and sexual bother scores. By one year after treatment, EPIC urinary, bowel, and sexual scores had increased and only the bowel overall and bowel bother scores remained significantly below baseline values.

Conclusions

HDR brachytherapy monotherapy is well-tolerated in patients with low and favorable intermediate risk prostate cancer. EPIC urinary and sexual domain scores returned to close to baseline 12 months after HDR brachytherapy.     

Atrial contribution to ventricular filling in mitral stenosis

BACKGROUND. The importance of the contribution of atrial systole to ventricular filling in mitral stenosis is controversial. The cause of reduced cardiac output following the onset of atrial fibrillation may be due to an increased heart rate, a loss of booster pump function, or both. METHODS AND RESULTS. We studied the atrial contribution to filling under a variety of conditions by combining noninvasive studies of patients with computer modeling. Thirty patients in sinus rhythm with mild-to-severe stenosis were studied with two-dimensional and Doppler echocardiography for measurement of mitral flow velocity and mitral valve area (MVA). The mean +/- SD atrial contribution to left ventricular filling volume was 18 +/- 10% and varied inversely with mitral resistance. Patients with mild mitral stenosis (MVA, 1.8 +/- 0.7 cm2) and severe mitral stenosis (MVA, 0.9 +/- 0.2 cm2) had atrial contributions of 29 +/- 4% and 9 +/- 5%, respectively. The pathophysiological mechanisms responsible for these trends were further investigated by the computer model. In modeled severe mitral stenosis, increasing heart rate from 75 to 150 beats/min caused an increase of 5.2 mm Hg in mean left atrial pressure, whereas loss of atrial contraction at a heart rate of 150 beats/min caused only a 1.3 mm Hg increase. CONCLUSIONS. The atrial booster pump contributes less to ventricular filling in mitral stenosis than in the normal heart, and the loss of atrial pump function is less important than the effect of increasing heart rate as the cause of decompensation during atrial fibrillation.     

Methods for long-term 17β-estradiol administration to mice

Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets.     

Exploring Binge Drinking and Drug Use among American Indians: Data from Adolescent Focus Groups

Background: Risk factors for binge substance use and non-suicidal self-injury (NSSI) are similar, suggesting the importance of exploring how binge substance use and self-injury interrelate. Objectives: To gain insight from a sample of American Indian (AI) adolescents regarding how binge drinking and drug use function in their lives, including as overlapping forms of self-injury, and to identify community-based ideas for dual prevention strategies. Methods: A total of N?=?58 White Mountain Apache (Apache) adolescents participated in ten mixed gender (n?=?33 males, 55.9%) focus group discussions. Results were interpreted and categorized by Apache researchers and compared to Nock's behavioral model of NSSI. Results: Participants reported substance use most commonly with "family" and "friends," "at a house," or "around the community." Substance use was not confined to a particular time of day, and often occurred "at school." Commonly endorsed reasons fell into two main categories: "to avoid problems" or "to reduce negative feelings," versus "to be cool" or "to feel part of a group." All adolescents but one thought that some youths use substances excessively as a way to harm/injure themselves (n?=?25 responses). Prevention approaches included encouraging healthy relationships, teaching about consequences of use, providing alternative recreation, and changing/enforcing laws on the reservation. Conclusion: Tribal-specific data support the idea that binge substance use sometimes functions as a form of self-injury. Home/school environments are critical prevention settings, in addition to improved law enforcement and increased recreation. Scientific Significance: Understanding possible shared root causes and functions of binge substance use and self-injury may advance integrated prevention approaches.     

Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.