Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage

OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher's exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.     

Simulation of mixed-mode I/III stable tearing crack growth events using the cohesive zone model approach

A cohesive zone model (CZM) approach is applied to simulate mixed-mode I/III stable tearing crack growth events in specimens made of 6061-T6 aluminum alloy and GM 6208 steel. The materials are treated as elastic–plastic following the \(J_{2}\) flow theory of plasticity, and the triangular cohesive law is employed to describe the traction-separation relation in the cohesive zone ahead of crack front. A hybrid numerical/experimental approach is employed in simulations using 3D finite element method. For each material, CZM parameter values are chosen by matching simulation prediction with experimental measurement (Yan et al. in Int J Fract 144:297–321, 2009), of the crack extension-time curve for the \(30^{\circ }\) mixed-mode I/III stable tearing crack growth test. With the same sets of CZM parameter values, simulations are performed for the \(60^{\circ }\) loading cases. Good agreements are reached between simulation predictions of the crack extension-time curve and experimental results. The variations of CTOD with crack extension are calculated from CZM simulations under both \(30^{\circ }\) and \(60^{\circ }\) mixed-mode I/III conditions for the aluminum alloy and steel respectively. The predictions agree well with experimental measurements (Yan et al. in Int J Fract 144:297–321, 2009). The findings of the current study demonstrate the applicability of the CZM approach in mixed-mode I/III stable tearing simulations and reaffirm the connection between CTOD and CZM based simulation approaches shown previously for mixed-mode I/II crack growth events.     

Modeling of mixed-mode crack growth in ductile thin sheets under combined in-plane and out-of-plane loading

This paper describes a modeling approach for analyzing mixed-mode crack growth events in ductile thin-sheet materials under large deformation and combined in-plane and out-of-plane loading conditions. The remote mixed-mode I/III loading leads to local mixed-mode I/II/III fields near the crack front. Making use of full-field surface deformation measurements, finite element models of mixed-mode I/III stable tearing events in thin-sheet specimens have been developed. Model predictions have been compared with experimental measurements (a) just prior to initial crack growth and (b) during stable tearing crack growth. Analyses of curvilinear crack growth events are carried out using a nodal release option or a local re-meshing option and using a generalized CTOD parameter with experimentally measured critical CTOD values. Results of this study suggest that the modeling approach can be employed to numerically re-construct experimental crack growth events in thin plate specimens. This offers a viable means of analyzing and understanding the mixed-mode crack growth events and provides a tool for further investigations of 3D crack front fields (which are otherwise unavailable experimentally) and for the study of fracture criteria for stable tearing events.     

Investigation of diagnostic techniques for metal oxide surge arresters

Gapless metal oxide surge arresters (MOSA) have been available in the market for many years since they were first introduced in the 1970's. The aim of this study is to investigate some reliable diagnostic techniques to assess the condition of a metal oxide surge arrester when subjected to severe lightning strikes in the field. A number of nondestructive and destructive diagnostic techniques for metal oxide surge arrester (MOSA) are discussed in this paper. The nondestructive techniques include the standard 1 mA reference voltage, lightning impulse discharge residual voltage and a number of modern diagnostics based on polarization methods: Return voltage and polarization/depolarization current measurements. In order to observe, analyze and correctly explain the degradation phenomena, a number of destructive techniques based on microstructure observation are also conducted. The techniques include optical microscopy, scanning electron microscopy, X-Ray diffraction and energy dispersive spectrometry. The single and multipulse currents of 8/20 mus wave shape were used to artificially degrade the MOSA. The before and after diagnostic results of the nondestructive and destructive techniques are presented and interpreted to understand the aging mechanism in MOSA. The importance of modern nondestructive electrical diagnostics based on polarization methods is validated by test results and is highlighted in detail in this paper. Finally the correlation of the results of different diagnostic techniques with each other and with the results of standard techniques is discussed     

Gas chromatographic-mass spectrometric discrimination between 8-iso-prostaglandin E2 and prostaglandin E2 through derivatization by O-(2,3,4,5,6-Pentafluorobenzyl)hydroxyl amine

The use of genomic libraries maintained in arrayed format is becoming a more and more popular tool for the analysis of molecular evolution and comparative molecular development. Being able to use already existing reference libraries considerably reduces the work load, and if results are made publicly available, it will facilitate in silica experiments in the future. Here we describe the construction and preliminary characterization of six cosmid libraries of different chordate species, Ciona intestinalis (Hemichordate), Branchiostoma floridae (Cephalochordate), Lampetra fluviatilis (Cyclostoma), Xiphophorus maculatus, and Danio rerio (Osteichthyes) in Lawrist7 and Fugu rubripes in Lawrist4.     

Effect of acute hypoglycemia on visual information processing in adults with type 1 diabetes mellitus

Acute hypoglycemia in people with type 1 (insulin-dependent) diabetes mellitus causes general impairment in cognitive performance. The effects on more specific cognitive processes are less well defined. Acute hypoglycemia has been shown to impair visual information processing in nondiabetic human subjects and has now been examined in 16 adult subjects with type 1 diabetes. All subjects had normal visual acuity and no diabetic retinopathy, and their median (range) age was 24 (18-47) years with a median (range) duration of type 1 diabetes of 8 (2-18) years and a mean (SD) HbA1c of 8.5 (1.3)%. A hyperinsulinemic glucose clamp technique was used to maintain arterialized blood glucose at 5.0 mmol l(-1), and on separate test days, either euglycemia was continued or hypoglycemia (2.6 mmol l(-1)) was induced. During each condition subjects performed tests of visual processing and cognitive function. Hypoglycemia caused a significant disruption in general cognitive ability as assessed by digit symbol (p < 0.001) and trail-making B (p < 0.05) tasks. Conventional measures of visual acuity were unaffected by hypoglycemia, but visual information processing deteriorated significantly as indexed by inspection time (p < 0.005) and visual change detection (p < 0.01). Contrast sensitivity tended to deteriorate during hypoglycemia (p = 0.06). In conclusion, hypoglycemia impairs important aspects of early visual information processing and contrast sensitivity in adults with type 1 diabetes. Further research is needed to evaluate the functional relevance of such changes for everyday tasks that require the intake of visual information at speed and under conditions of low contrast.     

Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes. Implications for peptide-based immunotherapy

Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (approximately 20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-1(27-35), G9(154), and G9(280) Flu M1(58-66)) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.     

Comparison of methods for identifying transcription units and transcription map of the Werner syndrome gene region

OBJECTIVE: The audiologic presentation of vestibular schwannoma (VS) associated with neurofibromatosis type 2 (NF2) has not been well characterized. The goal of this study was to investigate the audiologic features of NF2-associated VS and to determine their relationship to the size of the tumor. STUDY DESIGN: A retrospective case review. SETTING: Quaternary governmental medical research institute evaluating patients fitting specific criteria for ongoing clinical studies. PATIENTS: Audiologic and magnetic resonance imaging data were available for 40 patients (25 males, 15 females), with an average age of 32 years, who had been recruited for ongoing clinical and genetic studies of NF2. MAIN OUTCOME MEASURES: The audiologic profile and magnetic resonance imaging characteristic of tumor were retrospectively reviewed. RESULTS: The average size of the tumor at presentation was 7.26 +/- 16.58 cm3 and measured 1.2, 1.6, and 1.1 cm in the anterior/posterior, lateral/medial, and superior/inferior dimensions, respectively. An increase in lateral/medial size of the tumor most significantly correlated with deterioration in mid- (1,000-2,000 Hz) and high- (4,000-8,000 Hz) frequency hearing levels, elevated speech reception threshold, and prolonged auditory brain stem response waves III and V latency. CONCLUSIONS: Patients with NF2 demonstrate a more predictable audiologic profile for a given size tumor than has been previously described with spontaneous or sporadic VS.