Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

Background Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and bacterial infection risk in cirrhotic patients and potential underlying mechanisms in complementary patient and animal models. Materials and methods Bacterial overgrowth was determined in jejunum of 30 rats randomly allocated to 6-week PPI treatment, gastrectomy or no treatment. In 84 consecutive cirrhotic patients, bacterial infection risk was prospectively assessed and related to PPI use. Intestinal permeability was determined by polyethylene glycol (PEG) test in nine healthy individuals and 12 cirrhotic patients. Results Bacterial overgrowth was much more common in jejunum of rats treated with PPI or gastrectomy compared with nontreated rats. Twenty-four patients (29%) developed a bacterial infection during a median follow-up of 28months. Although PPI users tended to experience infection more often than patients without PPI therapy, PPI use was not an independent predictor of bacterial infection (HR 1·2, 95% CI 0·5-3·0, P=0·72), after correction for Child-Pugh class (HR 3·6, 95% CI 1·5-8·7, P=0·004) and age (HR 1·05, 95%CI 1·01-1·09, P=0·02). In cirrhotic patients, 24-h urinary recovery of PEGs 1500 and 3350 was significantly higher compared with healthy controls. Conclusions Although in our animal model PPIs induced intestinal overgrowth, stage of liver disease rather than PPI use was the predominant factor determining infection risk in cirrhotic patients. Increased intestinal permeability may be a factor contributing to infection risk

Medicine in words and numbers: a cross-sectional survey comparing probability assessment scales

Contains fulltext : 56355.pdf ( ) (Open Access)Background / In the complex domain of medical decision making, reasoning under uncertainty can benefit from supporting tools. Automated decision support tools often build upon mathematical models, such as Bayesian networks. These networks require probabilities which often have to be assessed by experts in the domain of application. Probability response scales can be used to support the assessment process. We compare assessments obtained with different types of response scale. Methods / General practitioners (GPs) gave assessments on and preferences for three different probability response scales: a numerical scale, a scale with only verbal labels, and a combined verbal-numerical scale we had designed ourselves. Standard analyses of variance were performed. Results / No differences in assessments over the three response scales were found. Preferences for type of scale differed: the less experienced GPs preferred the verbal scale, the most experienced preferred the numerical scale, with the groups in between having a preference for the combined verbal-numerical scale. Conclusion / We conclude that all three response scales are equally suitable for supporting probability assessment. The combined verbal-numerical scale is a good choice for aiding the process, since it offers numerical labels to those who prefer numbers and verbal labels to those who prefer words, and accommodates both more and less experienced professionals.8 p

Small bowel motility affects glucose absorption in a healthy man

WSTĘP. Celem pracy było wyjaśnienie związku pomiędzy motoryką dwunastnicy i jelita cienkiego a wchłanianiem glukozy oraz ustalenie wpływu zmiany motoryki jelita cienkiego na wchłanianie glukozy po zastosowaniu substancji prokinetycznej - cizaprydu. MATERIAŁ I METODY. W badaniu wzięło udział 7 zdrowych mężczyzn, których średnia wieku wynosiła 22 lata. W sposób randomizowany badani otrzymywali cizapryd 10 mg 3 razy dziennie lub placebo, przez 3 dni. Po 2 tygodniach powtarzano próbę z drugim preparatem. Rano 3 dnia badania wykonywano manometrię z użyciem 18-kanałowego cewnika, wprowadzonego do dwunastnicy. Przez 30 minut badani otrzymywali przez cewnik płynną odżywkę (3 kcal/min), a następnie bolus analogu glukozy (3-OMG, 3-O-metyloglukozę). W celu oceny kinetyki wchłaniania oznaczano w osoczu stężenia 3-OMG. WYNIKI. Pole pod krzywą stężenia 3-OMG w pierwszych 30 minutach po podaniu dojelitowym było zależne od liczby ruchów robaczkowych rozchodzących się ortodromowo (r = 0,49, p < 0,05), ale nie wykazano związku ze stężeniem szczytowym, czasem do osiągnięcia stężenia szczytowego ani frakcją wchłoniętą. Średnia amplituda ruchów robaczkowych była wyższa przy podawaniu cizaprydu niż placebo (p < 0,05), ale powrót motoryki w okresie międzyposiłkowym, liczba ruchów robaczkowych i ich propagacja oraz charakterystyka wchłaniania 3-OMG były podobne przy stosowaniu cizaprydu i placebo. W obu typach leczenia propagacja ruchów robaczkowych w ponad 60% wynosiła jedynie 1,5 cm. WNIOSKI. Absorpcja glukozy w jelicie cienkim człowieka wiąże się z propagacją aktywności skurczowej jelita w zakresie krótkich odcinków. Cizapryd zwiększa amplitudę ruchów robaczkowych, ale nie wpływa na ich organizację ani na wchłanianie 3-OMG.INTRODUCTION. To investigate the relationship between duodenojejunal motor activity and glucose absorption and to evaluate the effect of modification of duodenojejunal motility on glucose absorption by using the prokinetic drug cisapride. MATERIAL AND METHODS. We examined seven healthy males, mean age 22 years, who were treated with cisapride 10 mg t.i.d. and placebo during 3 days in a randomized order, with a 2-week time interval. Duodenojejunal manometry was performed after each treatment on the morning of day 3, using an 18-lumen catheter. A liquid nutrient (3 kcal/min) was administered intraduodenally for 30 min, followed by a bolus of the glucose analog 3-O-methylglucose (3-OMG). Plasma 3-OMG concentrations were measured to assess absorption kinetics. RESULTS. The area under the 3-OMG concentration curve in the first 30 min after infusion was related to the number of antegrade propagated pressure waves (r = 0.49, P < 0.05), but not to the peak concentration, time to peak, and absorption fraction. The mean amplitude of pressure waves was higher during cisapride than placebo (P < 0.05), but the reoccurrence of interdigestive motility, numbers of pressure waves, and propagated pressure waves, as well as 3-OMG absorption characteristics, were not significantly different between the two treatments. During both treatments > 60% of antegrade propagated pressure waves were propagated over a very short distance (1.5 cm). CONCLUSIONS. Glucose absorption in the human small intestine is related to short-traveling propagated intestinal contractile activity. Cisapride increases the amplitude of pressure waves, but does not affect the organization of pressure waves or the absorption of 3-OMG

Asymmetry in the renewal of molecular classes of phosphatidylcholine in the rat-erythrocyte membrane

1. 1. Rat-blood phospholipids were labeled in vivo with [32P]phosphate. The erythrocytes were treated with phospholipase A2 plus sphingomyelinase to discriminate between the labeling patterns of the phospholipids from the inner and outer layer of the membrane. 2. 2. The specific activities of the more unsaturated classes of phosphatidylcholine were higher in the outer layer of the erythrocyte membrane than in the inner layer. The disaturated class, however, had the highest specific activity in the inner layer. 3. 3. After incubating 32P-labeled erythrocytes in unlabeled plasma, the labeling pattern recovered in the molecular classes of plasma phosphatidylcholine was very similar to that of the phosphatidylcholines in the outer layer of the erythrocyte membrane. 4. 4. It is proposed that the exchange of phosphatidylcholines between plasma and the outer layer of the erythrocyte is mainly responsible for the renewal of the unsaturated phosphatidylcholines of the erythrocyte, and that the acylation activity of the erythrocyte is directed towards the formation of disaturated phosphatidylcholines at the inside of the membrane

Asymmetry in the renewal of molecular classes of phosphatidylcholine in the rat-erythrocyte membrane

1. 1. Rat-blood phospholipids were labeled in vivo with [32P]phosphate. The erythrocytes were treated with phospholipase A2 plus sphingomyelinase to discriminate between the labeling patterns of the phospholipids from the inner and outer layer of the membrane. 2. 2. The specific activities of the more unsaturated classes of phosphatidylcholine were higher in the outer layer of the erythrocyte membrane than in the inner layer. The disaturated class, however, had the highest specific activity in the inner layer. 3. 3. After incubating 32P-labeled erythrocytes in unlabeled plasma, the labeling pattern recovered in the molecular classes of plasma phosphatidylcholine was very similar to that of the phosphatidylcholines in the outer layer of the erythrocyte membrane. 4. 4. It is proposed that the exchange of phosphatidylcholines between plasma and the outer layer of the erythrocyte is mainly responsible for the renewal of the unsaturated phosphatidylcholines of the erythrocyte, and that the acylation activity of the erythrocyte is directed towards the formation of disaturated phosphatidylcholines at the inside of the membrane

Bone healing during lower limb lengthening by distraction epiphysiolysis

A study of limb lengthening by distraction epiphysiolysis in the rabbit tibia is presented. A special external distraction device was developed that allowed 10 mm lengthening of the leg. Bone formation in the elongated zone was studied by computed tomography and [99mTc] methylene diphosphate (MDP) scintigraphy. Computed tomography showed bone formation proceeding for several weeks after the end of the distraction period, followed by a decrease in the amount of bone during a remodeling phase leading to the formation of a solid cortical structure. The uptake of [99mTc]MDP increased parallel to, but preceeding the actual accretion of bone, followed by a decrease during the bone remodeling phase. Uptake of the tracer will partly reflect bone metabolism, but other factors, like trauma, determine much of the uptake