Gastro 2013 APDW/WCOG Shanghai Working Party Report: Chronic diarrhea: Definition,classification, diagnosis

Diarrhea is best defined as passage of loose stools often with more frequent bowel movements. For clinical purposes, the Bristol Stool Form Scale works well to distinguish stool form and to identify loose stools. Laboratory testing of stool consistency has lagged behind. Acute diarrhea is likely to be due to infection and to be self‐limited. As diarrhea becomes chronic, it is less likely to be due to infection; duration of 1 month seems to work well as a cut‐off for chronic diarrhea, but detailed scientific knowledge is missing about the utility of this definition. In addition to duration of diarrhea, classifications by presenting scenario, by pathophysiology, and by stool characteristics (e.g. watery, fatty, or inflammatory) may help the canny clinician refine the differential diagnosis of chronic diarrhea. In this regard, a careful history remains the essential part of the evaluation of a patient with diarrhea. Imaging the intestine with endoscopy and radiographic techniques is useful, and biopsy of the small intestine and colon for histological assessment provides key diagnostic information. Endomicroscopy and molecular pathology are only now being explored for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is increasing; aside from a handful of well‐described infections because of pathogens, little is known about alterations in the microbiome in chronic diarrhea. Serological tests have well‐defined roles in the diagnosis of celiac disease but have less clearly defined application in autoimmune enteropathies and inflammatory bowel disease. Measurement of peptide hormones is of value in the diagnosis and management of endocrine tumors causing diarrhea, but these are so rare that these tests are of little value in screening because there will be many more false‐positives than true‐positive results. Chemical analysis of stools is of use in classifying chronic diarrhea and may limit the differential diagnosis that must be considered, but interpretation of the results is still evolving. Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial overgrowth, and intestinal transit are fraught with technical limitations that decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption have had limited utility beyond empirical trials of bile acid sequestrants.     

Cardiac consequences of renal transplantation: changes in left ventricular morphology and function

To characterize changes in left ventricular morphology and function associated with renal transplantation, noninvasive cardiac evaluations were performed in 41 adults at the time of surgery and at follow-up. At the time of transplantation, 36 patients had undergone hemodialysis through a fistula for 2.3 +/- 2.5 years (mean +/- SD); their hematocrit level was 26 +/- 6% and systolic blood pressure was 151 +/- 19 mm Hg. Perioperatively, left ventricular hypertrophy was present in 93% of patients by echocardiography, but in only 37% by electrocardiography. Abnormal left ventricular diastolic function was present in 67% of patients and indicated a high risk for perioperative pulmonary edema. At follow-up (1.5 +/- 1.4 years), mean hematocrit level increased to 39 +/- 7%, systolic blood pressure decreased to 132 +/- 14 mm Hg and spontaneous closure of the fistula occurred in 13 patients. Left ventricular mass by echocardiography decreased from 237 +/- 66 to 182 +/- 47 g (p less than 0.001), a decrease of 23%. Left ventricular volumes and cardiac index also decreased significantly, reflecting the rapid resolution of a pretransplant high output state. Despite proportionate regression of left ventricular hypertrophy within months of transplantation, diastolic function did not improve. The significant regression of left ventricular hypertrophy that occurs after renal transplantation may help explain the improved cardiovascular survival of patients with a renal transplant over that of patients on long-term dialysis.     

The echo-transponder electrode catheter: a new method for mapping the left ventricle

The ability to locate catheter position in the left ventricle with respect to endocardial landmarks might enhance the accuracy of ventricular tachycardia mapping. An echo-transponder system (Telectronics, Inc.) was compared with biplane fluoroscopy for left ventricular endocardial mapping. A 6F electrode catheter was modified with the addition of a piezoelectric crystal 5 mm from the tip. This crystal was connected to a transponder that received and transmitted ultrasound, resulting in a discrete artifact on the two-dimensional echocardiographic image corresponding to the position of the catheter tip. Catheters were introduced percutaneously into the left ventricle of nine anesthetized dogs. Two-dimensional echo-transponder and biplane fluoroscopic images were recorded on videotape with the catheter at multiple endocardial sites. Catheter location was marked by delivering radiofrequency current to the distal electrode, creating a small endocardial lesion. Catheter location by echo-transponder and by fluoroscopy were compared with lesion location without knowledge of other data. Location by echo-transponder was 8.7 +/- 5.1 mm from the center of the radiofrequency lesion versus 14 + 7.8 mm by fluoroscopy (n = 15, p = 0.023). Echo-transponder localization is more precise than is biplane fluoroscopy and may enhance the accuracy of left ventricular electrophysiologic mapping.     

Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava

To evaluate a simple noninvasive means of estimating right atrial (RA) pressure, the respiratory motion of the inferior vena cava (IVC) was analyzed by 2-dimensional echocardiography in 83 patients. Expiratory and inspiratory IVC diameters and percent collapse (caval index) were measured in subcostal views within 2 cm of the right atrium. Parameters were correlated with RA pressure by flotation catheter within 24 hours of the echocardiogram (38 were simultaneous). Correlations between RA pressure (range 0 to 28 mm Hg), expiratory and inspiratory diameters and caval index were 0.48, 0.71 and 0.75, respectively. Of 48 patients with caval indexes less than 50%, 41 (89%) had RA pressure greater than or equal to 10 mm Hg (mean +/- standard deviation, 15 +/- 6), while 30 of 35 patients (86%) with caval indexes greater than or equal to 50% had RA pressure less than 10 mm Hg (mean 6 +/- 5). Sensitivity and specificity for discrimination of RA pressure greater than or equal to or less than 10 mm Hg were maximized at the 50% level of collapse. Thus, IVC respiratory collapse on echocardiography is easily imaged and can be used to estimate RA pressure. A caval index greater than or equal to 50% indicates RA pressure less than 10 mm Hg, and caval indexes less than 50% indicate RA pressure greater than or equal to 10 Hg.     

Changes in regional left atrial function with aging: evaluation by Doppler tissue imaging.

AIMS: This study applies pulsed wave Doppler tissue imaging and colour Doppler tissue imaging to study changes in atrial function with ageing. We tested the following hypotheses: (1) pulsed wave Doppler tissue imaging can detect global changes of left atrial function associated with ageing similar to standard echocardiographic methods, (2) colour Doppler tissue imaging can reproducibly detect regional changes in atrial function (wall motion) of the normal young and normal aging atrium. METHODS AND RESULT: We studied 92 healthy subjects, divided into Group B (>or=50 years) and Group A (<50 years). As a reference standard the conventional measures of atrial function were determined: peak mitral A wave velocity, A wave velocity time integral, atrial emptying fraction and atrial ejection force. Pulsed wave Doppler tissue imaging estimated atrial contraction velocity (A' velocity) in late diastolic and segmental atrial contraction was determined by colour Doppler tissue imaging. A' velocities were significantly higher in Group B vs Group A (9.8+/-1.8 vs 8.5+/-1.5cm/s; P=0.0005). A' velocity correlated with atrial fraction (r=0.28; P=0.007) and atrial ejection force (r=0.21; P=0.04). Age correlated significantly with atrial ejection force (r=0.47; P=0.0001), atrial fraction (r=0.61; P=0.0001) and A' velocity (r=0.4; P=0.0002). Longitudinal segmental atrial contraction using colour Doppler tissue imaging showed an annular to superior segment decremental gradient with contraction velocities higher in Group B vs Group A. CONCLUSION: Pulsed wave Doppler tissue imaging and colour Doppler tissue imaging are reproducible and readily obtained parameters that provide unique data about global and segmental atrial contraction. In this study, changes in atrial contraction with aging were consistent with increased atrial contribution to filling accomplished by augmented atrial contractility.     

Outbreak-specific monovalent/bivalent vaccination to control and eradicate virulent ovine footrot

Footrot is a contagious disease of small ruminants which is caused by the bacterium Dichelobacter nodosus. In its virulent form there are severe economic losses and a very significant animal welfare issue. Sheep and goats can be vaccinated for treatment and prevention of the disease. There are 10 different serogroups of D. nodosus (A–I and M) and immunity is serogroup-specific. When all 10 serogroups are presented together in a vaccine, protection persists for only a few months due to “antigenic competition”. Consequently we evaluated the use of sequential monovalent or bivalent vaccines to control/eliminate/eradicate virulent footrot in a longitudinal intervention study on 12 commercial farms in southeast Australia with flock sizes of approximately 1200–4200 sheep. Overall, virulent footrot was eradicated from 4 of the flocks, 2 of which had 2 serogroups, and the others 4 or 5 serogroups. Where there were only 1 or 2 serogroups (3 farms) the clinical response was rapid and dramatic; prevalence was reduced from 45 to 50% before vaccination to 0% (2 farms) or 0.4% (1 farm) after one round of vaccination. In the remaining 9 flocks there were more than 2 serogroups and successive bivalent vaccines were administered leading to eradication of virulent footrot on 2 farms over 4 years and control of the disease on all but 3 of the others. Of the latter farms, 1 discontinued, and 2 initially had poor response to vaccine due to misdiagnosis of serogroup ‘M’, which was previously unknown in Australia. Control was achieved after administration of a serogroup M vaccine. These results provide clear evidence for control, elimination and eradication of virulent footrot by outbreak-specific vaccination in Australia.     

The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding

Using a murine challenge model, we previously determined that human papillomavirus (HPV) pseudovirions initially bind preferentially to the cervicovaginal basement membrane (BM) at sites of trauma. We now report that the capsids undergo a conformational change while bound to the BM that results in L2 cleavage by a proprotein convertase (PC), furin, and/or PC5/6, followed by the exposure of an N-terminal cross-neutralization L2 epitope and transfer of the capsids to the epithelial cell surface. Prevention of this exposure by PC inhibition results in detachment of the pseudovirions from the BM and their eventual loss from the tissue, thereby preventing infection. Pseudovirions whose L2 had been precleaved by furin can bypass the PC inhibition of binding and infectivity. Cleavage of heparan sulfate proteoglycans (HSPG) with heparinase III prevented infection and BM binding by the precleaved pseudovirions, but did not prevent them from binding robustly to cell surfaces. These results indicate that the infectious process has evolved so that the initial steps take place on the BM, in contrast to the typical viral infection that is initiated by binding to the cell surface. The data are consistent with a dynamic model of in vivo HPV infection in which a conformational change and PC cleavage on the BM allows transfer of virions from HSPG attachment factors to an L1-specific receptor on basal keratinocytes migrating into the site of trauma.