Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

A new reactor design combining enzyme, membrane and SC CO2: application to castor oil modification

International audienceThis study deals with the enzymatic modification of vegetable oils with the help of a newreactor design. Basically, the newreactor is a porous membrane contactor along and through which substrates are flowing. It is constituted from an enzymatic membrane and uses supercritical carbon dioxide (SC CO2) to fluidify the highly viscous substrates. The interesterification between castor oil triglycerides and methyl oleate catalysed by a lipase was chosen as a model reaction. It was preliminary tested and characterized in a batch reactor. Then the feasibility of the new process was demonstrated on a cross-flow filtration unit operating under SC CO2 conditions. The stability of the immobilized enzymes was checked and the influence of the transmembrane pressure on the reaction rate was observed

Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy. Cancer Res 65:1234-43.

Almost all cancers are preceded by a prolonged period of clinical latency during which a combination of cellular events helps move carcinogen-exposed cells towards a malignant phenotype. Hitherto, investigating the fate of premalignant cells in vivo remained strongly hampered by the fact that these cells are usually indistinguishable from their normal counterparts. Here, for the first time, we have designed a strategy able to reconstitute the replicative history of the bona fide premalignant clone in an animal model, the sheep experimentally infected with the lymphotropic bovine leukemia virus. We have shown that premalignant clones are early and clearly distinguished from other virus-exposed cells on the basis of their degree of clonal expansion and genetic instability. Detectable as early as 0.5 month after the beginning of virus exposure, premalignant cells displayed a two-step pattern of extensive clonal expansion together with a mutation load approximately 6 times higher than that of other virus-exposed cells that remained untransformed during the life span of investigated animals. There was no fixation of somatic mutations over time, suggesting that they regularly lead to cellular death, partly contributing to maintain a normal lymphocyte count during the prolonged premalignant stage. This equilibrium was finally broken after a period of 18.5 to 60 months of clinical latency, when a dramatic decrease in the genetic instability of premalignant cells coincided with a rapid increase in lymphocyte count and lymphoma onset

Direct comparison of the FibroScan XL and M probes for assessment of liver fibrosis in obese and nonobese patients

Esteban Durango,1,* Christian Dietrich,1,* Helmut Karl Seitz,1 Cornelia Ursula Kunz,2 Gilles T Pomier-Layrargues,3 Andres Duarte-Rojo,4 Melanie Beaton,5 Magdy Elkhashab,6 Robert P Myers,7 Sebastian Mueller1,3 1Department of Medicine and Center for Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, 2Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany; 3Liver Unit, Centre Hospitalier de l&#39;Universit&eacute; de Montr&eacute;al, H&ocirc;pital Saint-Luc, Montr&eacute;al, Quebec, 4Toronto Western Hospital Liver Centre, Toronto, Ontario; 5Multi-Organ Transplant Unit, University of Western Ontario, London, Ontario; 6The Toronto Liver Centre, Toronto, Ontario; 7Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada *These authors contributed equally to this researchBackground: A novel Fibroscan XL probe has recently been introduced and validated for obese patients, and has a diagnostic accuracy comparable with that of the standard M probe. The aim of this study was to analyze and understand the differences between these two probes in nonobese patients, to identify underlying causes for these differences, and to develop a practical algorithm to translate results for the XL probe to those for the M probe.Methods and results: Both probes were directly compared first in copolymer phantoms of varying stiffness (4.8, 11, and 40 kPa) and then in 371 obese and nonobese patients (body mass index, range 17.2&ndash;72.4) from German (n = 129) and Canadian (n = 242) centers. Liver stiffness values for both probes correlated better in phantoms than in patients (r = 0.98 versus 0.82, P < 0.001). Significantly more patients could be measured successfully using the XL probe than the M probe (98.4% versus 85.2%, respectively, P < 0.001) while the M probe produced a smaller interquartile range (21% versus 32%). Failure of the M probe to measure liver stiffness was not only observed in patients with a high body mass index and long skin-liver capsule distance but also in some nonobese patients (n = 10) due to quenching of the signal from subcutaneous fat tissue. In contrast with the phantoms, the XL probe consistently produced approximately 20% lower liver stiffness values in humans compared with the M probe. A long skin-liver capsule distance and a high degree of steatosis were responsible for this discordance. Adjustment of cutoff values for the XL probe (<5.5, 5.5&ndash;7, 7&ndash;10, and >10 kPa for F0, F1&ndash;2, F3, and F4 fibrosis, respectively) significantly improved agreement between the two probes from r = 0.655 to 0.679.Conclusion: Liver stiffness can be measured in significantly more obese and nonobese patients using the XL probe than the M probe. However, the XL probe is less accurate and adjusted cutoff values are required.Keywords: cirrhosis, liver fibrosis, liver stiffness, obesity, steatosis, transient elastography, M probe, XL prob