Paul W. Weber

Microbic superinfection in relapse of inflammatory bowel disease.

To assess the association between symptomatic relapse of inflammatory bowel disease (IBD) and superinfection with enteropathogenic microorganisms, we determined prospectively the incidence of infections with enteropathogenic bacteria, protozoa, and helminths in patients with confirmed longstanding IBD. Sixty-four patients with IBD (49 with Crohns disease [CD] and 15 with ulcerative colitis [UC]) were consecutively enrolled in the study when relapse occurred. Multiple biopsies for histological and microbiological investigations were taken from all patients who were evaluated by colonoscopy. Parallel stool specimens were investigated for the presence of enteropathogenic bacteria, protozoa, and helminths. In six patients, we detected Clostridium difficile or toxin B (five CD, one UC), in one patient Campylobacter jejuni (CD), and in another patient Salmonella typhimurium (UC). Enteropathogenic Escherichia coli were isolated from three patients. Investigation of biopsies for Mycobacteria, microscopic examination of stool samples for helminths, and immunofluorescence for chlamydia were negative in all patients. In summary, as we found enteropathogenic microorganisms so infrequently in patients with relapse of IBD, despite intensive microbiological screening by tissue sampling for detection of gut adherent bacteria, we believe that microorganisms play only a minor role in the exacerbation of IBD.

The Tubercles on Humpback Whales' Flippers: Application of Bio-Inspired Technology

The humpback whale (Megaptera novaeangliae) is exceptional among the large baleen whales in its ability to undertake aquabatic maneuvers to catch prey. Humpback whales utilize extremely mobile, wing-like flippers for banking and turning. Large rounded tubercles along the leading edge of the flipper are morphological structures that are unique in nature. The tubercles on the leading edge act as passive-flow control devices that improve performance and maneuverability of the flipper. Experimental analysis of finite wing models has demonstrated that the presence of tubercles produces a delay in the angle of attack until stall, thereby increasing maximum lift and decreasing drag. Possible fluid-dynamic mechanisms for improved performance include delay of stall through generation of a vortex and modification of the boundary layer, and increase in effective span by reduction of both spanwise flow and strength of the tip vortex. The tubercles provide a bio-inspired design that has commercial viability for wing-like structures. Control of passive flow has the advantages of eliminating complex, costly, high-maintenance, and heavy control mechanisms, while improving performance for lifting bodies in air and water. The tubercles on the leading edge can be applied to the design of watercraft, aircraft, ventilation fans, and windmills.

Acute Pancreatitis in Crohn's Disease

Pancreatitis as an extraintestinal manifestation of Crohns disease (CD) is controversial. We review the episodes of acute pancreatitis in patients with CD. Of 852 patients, 12 developed clinically overt pancreatitis, representing a frequency of 1.4% in a follow-up period of 10 years. In 10 patients, common causes of pancreatitis were excluded. In 2 patients, drug-induced disease (azathioprine, sulfasalazine) could not be ruled out. Recurrence of pancreatitis was observed in only 2 patients. Younger patients and those with active disease seemed more at risk for development of pancreatitis. If prednisolone was needed for treatment of active CD, no adverse effect was observed for the pancreatitis. Along with the clinical features, we studied autoantibodies against exocrine pancreas; the incidence of autoantibodies in patients with pancreatitis was the same as in the controls who did not develop pancreatic abnormalities. This does not support the hypothesis that acute pancreatitis in CD is associated with the formation of pancreatic autoantibodies.

Hypereosinophilic syndrome resembling chronic inflammatory bowel disease with primary sclerosing cholangitis.

Surgical patient who presented with chronic inflammation of the colon, and initially also the terminal ileum, accompanied by marked diarrhea, is described. Repeated high-dose steroid therapy was only temporarily successful, and symptoms recurred upon dose reduction. During the further course of the disease, a marked elevation of alkaline phosphatase and transaminases, as well as soft tissues swelling occurred. Clinically, the diagnosis of inflammatory bowel disease with primary sclerosing cholangitis was made. Irregularities in the walls of the common bile duct and the intrahepatic ducts seen at endoscopic retrograde cholangiopancreatography were consistent with the latter diagnosis. However, extreme eosinophilia of peripheral blood, bone marrow and bowel mucosa was present, and liver histology showed eosinophilic cholangiohepatitis. Under the diagnosis of hypereosinophilic syndrome with involvement of bowel, liver and biliary system, therapy with hydroxyurea was initiated. The patients condition improved promptly. Eosinophil count and liver enzymes have remained normal under long-term medication with 1.0 g per day of this drug.

Impaired pancreatic function in patients with Crohn's disease with and without pancreatic autoantibodies.

Pancreatic autoantibodies (PABs) are found in 31% of patients with Crohns disease (CD), but they do not correlate with the activity of intestinal disease or the incidence of acute pancreatitis. Exocrine pancreatic insufficiency has been observed in patients with CD. The aim of our study was to correlate the occurrence of PABs with exocrine pancreatic function to explore the clinical significance of these antibodies. Serum samples of 64 patients with CD were tested for PABs by indirect immunofluorescence. In addition, all patients were tested for exocrine pancreatic insufficiency by a fluorescein dilaurate test. PABs were detected in 26 of 64 patients (40%). The PAB-positive and -negative groups did not differ in clinical characteristics, such as age, sex, involvement of intestine, previous surgical interventions, drug therapy, and disease activity. Seven of the antibody-positive patients (27%) had impaired pancreatic function, in contrast to three of 38 PAB-negative patients (8%) (p < 0.05). In conclusion, exocrine pancreatic function is impaired significantly more often in PAB-positive than in PAB-negative patients. A prospective follow-up is required to determine whether PAB-positive patients are more likely to develop pancreatic insufficiency later in their course of disease.

Lift and drag performance of odontocete cetacean flippers

SUMMARY Cetaceans (whales, dolphins and porpoises) have evolved flippers that aid in effective locomotion through their aquatic environments. Differing evolutionary pressures upon cetaceans, including hunting and feeding requirements, and other factors such as animal mass and size have resulted in flippers that are unique among each species. Cetacean flippers may be viewed as being analogous to modern engineered hydrofoils, which have hydrodynamic properties such as lift coefficient, drag coefficient and associated efficiency. Field observations and the collection of biological samples have resulted in flipper geometry being known for most cetacean species. However, the hydrodynamic properties of cetacean flippers have not been rigorously examined and thus their performance properties are unknown. By conducting water tunnel testing using scale models of cetacean flippers derived via computed tomography (CT) scans, as well as computational fluid dynamic (CFD) simulations, we present a baseline work to describe the hydrodynamic properties of several cetacean flippers. We found that flippers of similar planform shape had similar hydrodynamic performance properties. Furthermore, one group of flippers of planform shape similar to modern swept wings was found to have lift coefficients that increased with angle of attack nonlinearly, which was caused by the onset of vortex-dominated lift. Drag coefficient versus angle of attack curves were found to be less dependent on planform shape. Our work represents a step towards the understanding of the association between performance, ecology, morphology and fluid mechanics based on the three-dimensional geometry of cetacean flippers.

Modifying Peripheral IV Catheters With Side Holes and Side Slits Results in Favorable Changes in Fluid Dynamic Properties During the Injection of Iodinated Contrast Material

OBJECTIVE The purpose of this study was to compare a standard peripheral end-hole angiocatheter with those modified with side holes or side slits using experimental optical techniques to qualitatively compare the contrast material exit jets and using numeric techniques to provide flow visualization and quantitative comparisons. MATERIALS AND METHODS A Schlieren imaging system was used to visualize the angiocatheter exit jet fluid dynamics at two different flow rates. Catheters were modified by drilling through-and-through side holes or by cutting slits into the catheters. A commercial computational fluid dynamics package was used to calculate numeric results for various vessel diameters and catheter orientations. RESULTS Experimental images showed that modifying standard peripheral IV angiocatheters with side holes or side slits qualitatively changed the overall flow field and caused the exiting jet to become less well defined. Numeric calculations showed that the addition of side holes or slits resulted in a 9-30% reduction of the velocity of contrast material exiting the end hole of the angiocatheter. With the catheter tip directed obliquely to the wall, the maximum wall shear stress was always highest for the unmodified catheter and was always lowest for the four-side-slit catheter. CONCLUSION Modified angiocatheters may have the potential to reduce extravasation events in patients by reducing vessel wall shear stress.

Contrast Material Administration Protocols for 64-MDCT Angiography: Altering Volume and Rate and Use of a Saline Chaser to Better Match the Imaging Window—Physiologic Phantom Study

OBJECTIVE The purpose of our study was to evaluate the effect of varying volumes and rates of contrast material, use of a saline chaser, and cardiac output on aortic enhancement characteristics in MDCT angiography (MDCTA) using a physiologic phantom. MATERIALS AND METHODS Volumes of 75, 100, and 125 mL of iopamidol, 370 mg I/mL, were administered at rates of 4, 6, and 8 mL/s. The effect of a saline chaser (50 mL of normal saline, 8 mL/s) was evaluated for each volume and rate combination. Normal, reduced (33% and 50%), and increased (25%) cardiac outputs were simulated. Peak aortic enhancement and duration of peak aortic enhancement were recorded. Analysis of variance models were run with these effects, and the estimated mean levels for the sets of factor combinations were determined. RESULTS Lowering the volume of contrast material resulted in reduced peak enhancement (example, -56.2 HU [p < 0.0001] with 75 vs 125 mL) and reduced duration of 75% peak enhancement (example, -9.0 seconds [p < 0.0001] with 75 vs 125 mL). Increasing the rate resulted in increased peak enhancement (example, 104.5 HU [p < 0.0001] with a rate of 8 vs 4 mL/s) and decreased duration of 75% peak enhancement (example, -13.0 seconds [p < 0.001]). Use of a saline chaser resulted in increased peak enhancement, and this increase was inversely proportional to contrast material volume. Peak enhancement increased when reduced cardiac output was simulated. Peak enhancement decreased when increased cardiac output was simulated. CONCLUSION Reducing contrast material volume from 125 to 75 mL, increasing the rate to 6 or 8 mL/s, and use of a saline chaser result in an aortic enhancement profile that better matches the approximately 5-second imaging window possible with 64-MDCTA of the abdomen and pelvis. Even smaller volumes of contrast material may be adequate in patients with reduced cardiac output.

Resolution and Severity in Decompression Illness

omegaWe review the terminology of decompression illness (DCI), investigations of residual symptoms of decompression sickness (DCS), and application of survival analysis for investigating DCI severity and resolution. The Type 1 and Type 2 DCS classifications were introduced in 1960 for compressed air workers and adapted for diving and altitude exposure with modifications based on clinical judgment concerning severity and therapy. In practice, these proved ambiguous, leading to recommendations that manifestations, not cases, be classified. A subsequent approach assigned individual scores to manifestations and correlated total case scores with the presence of residual symptoms after therapy. The next step used logistic regression to find the statistical association of manifestations to residual symptoms at a single point in time. Survival analysis, a common statistical method in clinical trials and longitudinal epidemiological studies, is a logical extension of logistic regression. The method applies to a continuum of resolution times, allows for time varying information, can manage cases lost to follow-up (censored), and has potential for investigating questions such as optimal therapy and DCI severity. There are operational implications as well. Appropriate definitions of mild and serious manifestations are essential for computing probabilistic decompression procedures where severity determines the DCS probability that is acceptable. Application of survival analysis to DCI data would require more specific case information than is commonly recorded.

Marginal DCS events: their relation to decompression and use in DCS models

We consider the nature and utility of marginal decompression sickness (DCS) events in fitting probabilistic decompression models to experimental dive trial data. Previous works have assigned various fractional weights to marginal DCS events, so that they contributed to probabilistic model parameter optimization, but less so than did full DCS events. Inclusion of fractional weight for marginal DCS events resulted in more conservative model predictions. We explore whether marginal DCS events are correlated with exposure to decompression or are randomly occurring events. Three null models are developed and compared with a known decompression model that is tuned on dive trial data containing only marginal DCS and non-DCS events. We further investigate the technique by which marginal DCS events were previously included in parameter optimization, explore the effects of fractional weighting of marginal DCS events on model optimization, and explore the rigor of combining data containing full and marginal DCS events for probabilistic DCS model optimization. We find that although marginal DCS events are related to exposure to decompression, empirical dive data containing marginal and full DCS events cannot be combined under a single DCS model. Furthermore, we find analytically that the optimal weight for a marginal DCS event is 0. Thus marginal DCS should be counted as no-DCS events when probabilistic DCS models are optimized with binomial likelihood functions. Specifically, our study finds that inclusion of marginal DCS events in model optimization to make the dive profiles more conservative is counterproductive and worsens the models fit to the full DCS data.