Is high prevalence of Echinococcus multilocularis in wild and domestic animals associated with disease incidence in humans?

We investigated a focus of highly endemic Echinococcus multilocularis infection to assess persistence of high endemicity in rural rodents, explore potential for parasite transmission to domestic carnivores, and assess (serologically) putative exposure versus infection frequency in inhabitants of the region. From spring 1993 to spring 1998, the prevalence of E. multilocularis in rodents was 9% to 39% for Arvicola terrestris and 10% to 21% for Microtus arvalis. From June 1996 to October 1997, 6 (7%) of 86 feral dogs and 1 of 33 cats living close to the region tested positive for intestinal E. multilocularis infection. Testing included egg detection by coproscopy, antigen detection by enzyme-linked immunosorbent assay (ELISA), and specific parasite DNA amplification by polymerase chain reaction. Thus, the presence of infected domestic carnivores can increase E. multilocularis exposure risk in humans. A seroepidemiologic survey of 2,943 blood donors in the area used specific Em2-ELISA. Comparative statistical analyses of seroprevalence and clinical incidence showed an increase in Em2-seroprevalence from 1986 and 1996-97 but no increase in clinical incidence of alveolar hydatid disease

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients

Background Aims: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. Methods: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. Results: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. Conclusions: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load - and therefore minimizes the risk of adverse events - may result in clinical efficacy should be investigated

Characterisation of an Adhesive-free Packaging System for Polymeric Microfluidic Biochemical Devices and Reactors

The development of microfluidic devices is an iterative process that involves series of improvements, which can be costly and time consuming. We present a packaging system which makes use of an accessible rapid prototyping method, and facilitates the rapid and reliable implementation of polymeric microfluidic device designs. The packaging system uses a modular design and is based on an adhesive-free connection of a reusable and stiff polymeric interface plate with a disposable, soft microfluidic chip under compression. We characterised the system by numerically and experimentally studying the effect of compression and key dimensions on burst pressure and flow rate. All parts are fabricated with readily available low-cost materials and micro-milling technology. The presented approach is both facilitating and systematising the fabrication of devices with different degrees of complexity; keeping assembly and interconnection simple and straightforward. Furthermore, minimising the time between a design and a finished working prototype yields rapid verification of microfluidic design concepts and testing of assays. Several chip designs were fabricated, then growth of stem cells and hydrodynamic vertical flow focusing in a microfluidic device were realised using our approach. Our approach minimises the need for re-development and re-testing of interface components; reducing cost and time requirements

Chandra X-ray Observations of the Spiral Galaxy M81

A Chandra X-Ray Observatory ACIS-S imaging observation is used to study the population of X-ray sources in the nearby Sab galaxy M81 (NGC 3031). A total of 177 sources are detected with 124 located within the D25 isophote to a limiting X-ray luminosity of 3e36 ergs/cm2/s. Source positions, count rates, luminosities in the 0.3-8.0 keV band, limiting optical magnitudes, and potential counterpart identifications are tabulated. Spectral and timing analysis of the 36 brightest sources are reported including the low-luminosity active galactic nucleus, SN 1993J, and the Einstein-discovered ultra-luminous X-ray source X6.Comment: 27 pages, 17 figures, 2 tables, submitted to Ap

Rationale Diuretikatherapie bei Patienten mit Leberzirrhose. [Rational diuretic therapy in patients with liver cirrhosis]

When ascites develops in a patient with liver cirrhosis his probability to survive the following two years amounts to 50%. It is determined essentially by the residual functional capacity of the liver. In 80 to 90% of patients ascites due to portal hypertension can be managed by salt restriction and diuretics. A daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because prerenal failure may become a threat. Aldosterone-antagonists are more efficient and have fewer side-effects than loop diuretics. The urinary ratio of Na/K may be used to adjust the therapy. They may lower portal hypertension by an additional direct effect on the vasculature. If diuretics are insufficient or when a rapid therapeutic success is needed, paracentesis of 4-6 l is a safe option if intravascular volume is substituted simultaneously with albumin. Only in the few patients whose ascites is intractable by the forementioned measures, alternatives such as peritoneo-, venous or porto-systemic shunts (nowadays mostly by interventional techniques via a transjugular catheter) should be evaluated. The only treatment which not only attacks ascites symptomatically but also corrects the underlying disease is liver transplantation

Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination

Risks and Challenges in Interpreting Simultaneous Analyses of Multiple Cytokines

Abstract Purpose: To determine the inherent risks of handling results below the lowest detectable value in the analysis of multiple cytokines in the aqueous humor of patients with retinal diseases by comparing possible statistical strategies to lower the risk of mis interpretation or over interpretation of results. Furthermore, in analyzing multiple cytokines simultaneously, the challenge of multiple comparison arises. Methods: The analyses were based on parallel testing of 43 cytokines in 58 aqueous humor samples from patients with macular hole or epiretinal membrane. Substitution of values below the detection limit with 0.1 ×, 0.5 ×, or 1.0× of the lowest level of quantitation was compared with handling as missing value. The impact of correction for multiple comparisons was assessed using the Holm correction. Results: When comparing macular hole with epiretinal membrane, not substituting the missing data revealed a difference (P < 0.05) for five compared with wight cytokines after their substitution, indicating an increased risk for under-estimating group differences (type II error). Correcting for multiple comparisons revealed a relevant risk of over estimating group differences (type I error). Conclusions: Physiologic cytokine concentrations in ocular fluids typically range at or below the lowest level of quantitation. Handling of results below this cutoff as missing leads to increased type II errors. Not correcting for multiple comparisons increases the risk of a type I error. Taken together, both harbor a systematic inherent risk of misinterpretation of the results

Cholate uptake in basolateral rat liver plasma membrane vesicles and in liposomes

The mechanism(s) and driving force(s) for hepatocellular uptake of the unconjugated bile acid cholate were investigated in isolated basolateral (sinusoidal) rat liver plasma membrane (blLPM) vesicles and in protein free liposomes. In blLPM vesicles both an inwardly directed Na+ gradient and a transmembrane pH difference (8.0 in/6.0 out) stimulated cholate uptake 2-3-fold above equilibrium uptake values (overshoot). While Na+ gradient driven cholate uptake could be inhibited by the anion transport inhibitor 4,4'-diisothiocyanato-2,2'-disulfonic acid stilbene (DIDS), the pH gradient dependent portion of cholate uptake was insensitive to DIDS, but could be inhibited by furosemide. Furthermore, initial rates (1-s values) of the pH gradient stimulated cholate uptake were linear with increasing substrate concentrations (no saturability). In liposomes a similar inside alkaline pH gradient also induced a transient DIDS insensitive/furosemide inhibitable intravesicular accumulation (approx. 2-fold) of cholate (overshoot). These findings confirm that hepatocellular uptake of cholate occurs in part via the common Na+/bile acid cotransport system. In addition, the data strongly indicate that in isolated membrane vesicles pH gradient driven cholate uptake represents nonionic diffusion rather than a carrier mediated process (Blitzer, B.L., Terzakis, C. and Scott, K.A. (1986) J. Biol. Chem. 261, 12042-12046). Since in the perfused liver DIDS inhibited uptake of both cholate and taurocholate to a similar extent, DIDS-insensitive pH gradient dependent membrane diffusion appears to be of minor significance for cholate uptake in the intact organ