Insulin-like growth factor I (IGF-I) and liver cirrhosis

Insulin-like growth factor I (IGF-I) is a polypeptide hormone secreted by multiple tissues in response to growth hormone (GH). It is partly responsible for GH activity, and also has glucose-lowering and anabolizing effects. Ninety percent of circulating IGF-I originates in the liver and has autocrine, paracrine, and endocrine effects, the latter on multiple tissues. Liver cirrhosis results in a progressive decline of hepatic IGF-I output, and this factor may become undetectable in advanced disease. Some cirrhosis complications, mainly those nutritional and metabolic in nature (insuline resistance, malnutrition, osteopenia, hypogonadism, intestinal disorders), may be at least partly related to this IGF-I deficiency, since some IGF-I effects represent a reverse image of cirrhosis complications. Despite this, IGF-I replacement therapy has been never suggested for cirrhosis. A number of experimental studies in cirrhotic rats showed that therapy using low-dose recombinant IGF-I exerts two types of effect on experimental cirrhosis: a) liver improvement driven by improved hepatocellular function, portal hypertension, and liver fibrosis; and b) cirrhosis-related extrahepatic disorder improvement driven by improved food efficiency, muscle mass, bone mass, gonadal function and structure, and intestinal function and structure, with a normalization of sugar and amino acid malabsorption, and improved intstinal barrier function, manifested by reduced endotoxemia and bacterial translocation. Subsequently, the first randomized, double-blind, placebo-controlled, pilot clinical trial in a small number of cirrhotic patients showed increased serum albumin and improved energy metabolism as a result of IGF-I use. Further clinical trials are needed to identify adequate IGF-I doses, administration duration and frequency, and the subgroup of cirrhotic patients who will benefit most from this replacement therapy

Predictors for outcome of failure of balloon dilatation in patients with achalasia

Background: Pneumatic balloon dilatation (PD) is a regular treatment modality for achalasia. The reported success rates of PD vary. Recurrent symptoms often require repeated PD or surgery. Objective: To identify predicting factors for symptom recurrence requiring repeated treatment. Methods: Between 1974 and 2006, 336 patients were treated with PD and included in this longitudinal cohort study. The median follow-up was 129 months (range 1-378). Recurrence of achalasia was defined as symptom recurrence in combination with increased lower oesophageal sphincter (LOS) pressure on manometry, requiring repeated treatment. Patient characteristics, results of timed barium oesophagram and manometry as well as baseline PD characteristics were evaluated as predictors of disease recurrence with Kaplan-Meier curves and Cox regression analysis. Results: 111 patients had symptom recurrence requiring repeated treatment. Symptoms recurred after a mean follow-up of 51 months (range 1-348). High recurrence percentages were found in patients younger than 21 years in whom the 5 and 10-year risks of recurrence were 64% and 72%, respectively. These risks were respectively 28% and 36% in patients with classic achalasia, respectively 48% and 60% in patients without complete obliteration of the balloon's waist during PD and respectively 25% and 33% in patients with a LOS pressure greater than 10 mm Hg at 3 months post-dilatation. These four predictors remained statistically significant in a multivariable Cox analysis. Conclusion: Although PD is an effective primary treatment in patients with primary achalasia, patients are at risk of recurrent disease, with this risk increasing during long-term follow-up. Young age at presentation, classic achalasia, high LOS pressure 3 months after PD and incomplete obliteration of the balloon's waist during PD are the most important predicting factors for the need for repeated treatment during follow-up. Patients who meet one or more of these characteristics may be considered earlier for alternative treatment, such as surgery

The LISA PathFinder DMU and Radiation Monitor

The LISA PathFinder DMU (Data Management Unit) flight model was formally accepted by ESA and ASD on 11 February 2010, after all hardware and software tests had been successfully completed. The diagnostics items are scheduled to be delivered by the end of 2010. In this paper we review the requirements and performance of this instrumentation, specially focusing on the Radiation Monitor and the DMU, as well as the status of their programmed use during mission operations, on which work is ongoing at the time of writing.Comment: 11 pages, 7 figures, prepared for the Proceedings of the 8th International LISA Symposium, Classical and Quantum Gravit

Assessment of oesophageal emptying in achalasia patients by intraluminal impedance monitoring

Oesophageal emptying can be assessed by radiographic and scintigraphic tests with radiation exposure or by multichannel intraluminal impedance monitoring (MII). The aim of this study was to evaluate the applicability of MII for the assessment of oesophageal emptying in achalasia patients. In 10 achalasia patients, impedance tracings were scored independently by three observers after ingestion of a 100-mL barium bolus. Bolus clearance time (BCT) and height of barium column were scored using fluoroscopic images acquired at 20-s intervals. All patients showed a low baseline impedance level in the distal oesophagus. Air trapping in the proximal oesophagus was detected in nine patients. BCT on MII was similar to that on fluoroscopy in 40-70% of the patients. Correlations between height of barium on fluoroscopy and fluid level on MII were poor to moderate at different time intervals. Concordance (Kendall's coefficient) between the three observers for assessment of fluid level on MII was 0.31 (P = 0.04) at 1 and 5 min, 0.26 (P = 0.08) at 10 and 0.44 (P = 0.01) at 15 min. We conclude that in achalasia patients, low baseline impedance levels and air entrapment in the proximal oesophagus limit the value of intraluminal impedance monitoring as a test of oesophageal emptying

LISA and LISA PathFinder, the endeavour to detect low frequency GWs

This is a review about LISA and its technology demonstrator, LISA PathFinder. We first describe the conceptual problems which need to be overcome in order to set up a working interferometric detector of low frequency Gravitational Waves (GW), then summarise the solutions to them as currently conceived by the LISA mission team. This will show that some of these solutions require new technological abilities which are still under development, and which need proper test before being fully implemented. LISA PathFinder (LPF) is the the testbed for such technologies. The final part of the paper will address the ideas and concepts behind the PathFinder as well as their impact on LISA.Comment: 25 pages, 21 figures, presented at the Spanish Relativity Meeting, Mallorca September 2006. Will be published in Journal of Physics: Conference Series, IOP. To be published in Journal of Physics: Conference Series, IO

Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C

BACKGROUND/AIMS: Oxidative stress could play a role in the pathogenesis of hepatitis C virus infection. We investigated the oxidant/antioxidant status in peripheral blood mononuclear cells from patients with chronic hepatitis C and controls. METHODS/RESULTS: Lipid peroxidation products and superoxide dismutase activity in peripheral blood mononuclear cells were higher in chronic hepatitis C patients than in healthy subjects while glutathione S-transferase activity was reduced in patients as compared to controls. Catalase, glutathione peroxidase and glutathione reductase were similar in chronic hepatitis C and normal individuals. No statistically significant differences were found between patients and controls with regard to glutathione levels in peripheral blood mononuclear cells, but 35% of patients with chronic hepatitis C showed values of glutathione and oxidized glutathione which were below and above, respectively, the limits of normal controls. Finally, the glutathione synthetic capacity of the cytosol of peripheral blood mononuclear cells was significantly higher in patients than in controls, indicating increased glutathione turnover in lymphocytes from patients with chronic hepatitis C. CONCLUSIONS: Oxidative stress is observed in peripheral blood mononuclear cells from chronic hepatitis C patients. This process might alter lymphocyte function and facilitate the chronicity of the infection

The diagnostics subsystem on board LISA PathFinder and LISA

The Data and Diagnostics Subsystem of the LTP hardware and software are at present essentially ready for delivery. In this presentation we intend to describe the scientific and technical aspects of this subsystem, which includes thermal diagnostics, magnetic diagnostics and a Radiation Monitor, as well as the prospects for their integration within the rest of the LTP. We also sketch a few lines of progress recently opened up towards the more demanding diagnostics requirements which will be needed for LISA.Comment: 11 pages, 5 figures, pdflatex, prepared for the Proceedings of the 7th International LISA Symposium (Barcelona, Spain, 16-20 June-2008), submitted to Classical and Quantum Gravit

In-flight Diagnostics in LISA Pathfinder

LISA PathFinder (LPF) will be flown with the objective to test in space key technologies for LISA. However its sensitivity goals are, for good reason, one order of magnitude less than those which LISA will have to meet, both in drag-free and optical metrology requirements, and in the observation frequency band. While the expected success of LPF will of course be of itself a major step forward to LISA, one might not forget that a further improvement by an order of magnitude in performance will still be needed. Clues for the last leap are to be derived from proper disentanglement of the various sources of noise which contribute to the total noise, as measured in flight during the PathFinder mission. This paper describes the principles, workings and requirements of one of the key tools to serve the above objective: the diagnostics subsystem. This consists in sets of temperature, magnetic field, and particle counter sensors, together with generators of controlled thermal and magnetic perturbations. At least during the commissioning phase, the latter will be used to identify feed-through coefficients between diagnostics sensor readings and associated actual noise contributions. A brief progress report of the current state of development of the diagnostics subsystem will be given as well.Peer Reviewe

In-flight Diagnostics in LISA Pathfinder

LISA PathFinder (LPF) will be flown with the objective to test in space key technologies for LISA. However its sensitivity goals are, for good reason, one order of magnitude less than those which LISA will have to meet, both in drag-free and optical metrology requirements, and in the observation frequency band. While the expected success of LPF will of course be of itself a major step forward to LISA, one might not forget that a further improvement by an order of magnitude in performance will still be needed. Clues for the last leap are to be derived from proper disentanglement of the various sources of noise which contribute to the total noise, as measured in flight during the PathFinder mission. This paper describes the principles, workings and requirements of one of the key tools to serve the above objective: the diagnostics subsystem. This consists in sets of temperature, magnetic field, and particle counter sensors, together with generators of controlled thermal and magnetic perturbations. At least during the commissioning phase, the latter will be used to identify feed-through coefficients between diagnostics sensor readings and associated actual noise contributions. A brief progress report of the current state of development of the diagnostics subsystem will be given as well.Peer Reviewe