Gastrointestinal wall thickening in patients with cirrhosis: frequency and patterns at contrast-enhanced CT

PURPOSE: To determine the frequency and patterns of gastrointestinal wall thickening at contrast material-enhanced computed tomography (CT) in patients with cirrhosis. MATERIALS AND METHODS: Three radiologists retrospectively assessed the contrast-enhanced abdominal CT scans of 77 patients with cirrhosis and 100 patients without cirrhosis for gastrointestinal wall thickening from the stomach through the descending colon. The frequencies of wall thickening were determined in the cirrhosis and in the control groups and were compared by using the Fisher exact test. The segmental distribution, symmetry, and enhancement pattern were evaluated in all patients with cirrhosis and gastrointestinal wall thickening. RESULTS: Gastrointestinal wall thickening was seen in 49 (64%) patients with cirrhosis and in seven (7%) control subjects (P <.005). The jejunum and ascending colon were the most common sites of gastrointestinal wall thickening; each was involved in 32 (42%; 95% CI: 30%, 53%) patients. The scans of 30 (61%; 95% CI: 47%, 75%) patients with gastrointestinal wall thickening showed multisegmental distribution. Gastrointestinal wall thickening was concentric and homogeneous in all patients with cirrhosis. CONCLUSION: Gastrointestinal wall thickening is common on contrast-enhanced abdominal CT scans in patients with cirrhosis. It frequently involves multiple segments. The jejunum and ascending colon are the most common sites of involvement.     

Tumor recurrence after radiofrequency thermal ablation of hepatic tumors: spectrum of findings on dual-phase contrast-enhanced CT.

OBJECTIVE: We conducted this study to determine the spectrum of CT findings of tumor recurrence after radiofrequency ablation of primary and secondary malignant hepatic tumors. MATERIALS AND METHODS: Twenty-five patients, 10 with hepatocellular carcinoma (HCC) and 15 patients with metastases who developed tumor recurrence after radiofrequency ablation of hepatic neoplasms, formed the study population. Three observers reviewed the CT scans of these patients and evaluated the location (local intrahepatic, remote intrahepatic, or extrahepatic) of all recurrent lesions and the morphology and enhancement characteristics of local intrahepatic recurrences. RESULTS: Local intrahepatic recurrences were seen in nine patients (90%) and 11 patients (73%); remote intrahepatic recurrences, in five patients (50%) and seven patients (45%); and extrahepatic recurrences, in zero and six patients (40%) with recurrent HCC and recurrent metastases, respectively. Of the 12 nodules of local intrahepatic recurrences in HCC and the 24 in metastases, the patterns of local intrahepatic recurrences were of nodular, halo, and gross enlargement types in eight (67%) and nine (38%), four (33%) and six (38%), and zero and nine (37%) nodules in HCC and hepatic metastases, respectively. The number of local intrahepatic recurrent lesions enhancing in the arterial phase was significantly greater in HCC. CONCLUSION: Tumor recurrences occurred at intra- and extrahepatic sites after radiofrequency ablation of hepatic neoplasms. The local intrahepatic recurrences appeared in three patterns: nodular, halo, or gross enlargement. The sites of recurrence and the morphologic patterns of local intrahepatic tumor recurrence differed between primary and secondary hepatic neoplasms.     

Molecular requirements for inhibition of the chemokine receptor CCR8 – probe-dependent allosteric interactions

BACKGROUND AND PURPOSE

Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes.

EXPERIMENTAL APPROACH

The compounds were tested as inverse agonists and as antagonists against CCL1-induced activity in Gα_i signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus-encoded antagonist MC148.

KEY RESULTS

All compounds were highly potent inverse agonists with EC₅₀ values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC₅₀ values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100-fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [¹²⁵I]-CCL1 (K_i 3.4–842 nM), whereas the affinities measured against [¹²⁵I]-MC148 were less widely spread (K_i 0.37–27 nM), and matched the inverse agonist potencies.

CONCLUSION AND IMPLICATIONS

Despite highly potent and direct effects as inverse agonists, competition-binding experiments against radiolabelled agonist and tests for antagonism revealed a probe-dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.     

The CASE survey: Patient and physician perceptions regarding asthma medication use and associated oropharyngeal symptoms

BACKGROUND:

Oropharyngeal (OP) symptoms are common in asthma patients using inhaled corticosteroids (ICSs) alone and in combination with a long-acting beta₂-agonist (LABA). Patterns of medication use, level of asthma control and association with OP symptoms are not often reported in a nonstudy setting.

OBJECTIVES:

To determine the prevalence of OP symptoms among adult asthma patients using ICSs alone and an ICS plus a LABA; to investigate the relationships between medication use, asthma control and OP symptoms; and to assess family physicians’ (FPs’) perceptions of the prevalence and management of OP symptoms.

METHODS:

A random telephone survey of 1003 asthma patients and 250 FPs treating asthma patients was conducted from February to March 2005 across Canada.

RESULTS:

Twenty-four per cent of patients experienced OP symptoms; 67% of them spoke to their FPs about the OP symptoms. Thirty-one per cent of patients who experienced OP symptoms stopped or reduced their dose of medication. OP symptoms were reported by 25% of patients using ICSs and 22% using an ICS plus a LABA. The incidence of OP symptoms was not affected by the choice of inhalation device (metered-dose inhaler versus dry powder inhaler) or the use of a spacer. Fifty-eight per cent of patients had uncontrolled asthma; patients achieving a lower level of general education were more likely to have poor control. Patients with uncontrolled asthma were more likely than those with controlled asthma to report OP symptoms (28% versus 18%, respectively; P<0.05). Eighty-nine per cent of FPs had patients who had reported OP symptoms to them. FPs estimated that 15% of their patients experienced OP symptoms and that compliance to treatment worsened in approximately 20% of them.

CONCLUSIONS:

The prevalence of OP symptoms in asthma patients using ICSs and an ICS plus a LABA is significant. OP symptoms were found to be associated with a reduced patient education level, with a likelihood of reducing or stopping medication, and with a less well-controlled asthma patient. While FPs recognized that a significant proportion of their asthma patients experience OP symptoms and that OP symptoms may affect compliance, they underestimated the prevalence of this problem.     

Antifilarial activity of ethyl acetate extract of Vitex negundo leaves in vitro

ObjectiveTo evaluate the possible antifilarial effect of ethyl acetate extract of Vitex negundo (Verbenaceae) leaves against Setaria cervi filarial parasite in vitro.MethodsIn vitro screening was done by the method of motility inhibition and MTT reduction assay with concentrations of 0.03 to 1.00 mg/mL for 2 to 24 h incubation periods respectively, for possible antifilarial effect by comparing with control.ResultsIn motility assay, complete inhibition of motility was observed and in MTT reduction assay which gave >50% reduction for concentrations 0.20, 0.50 and 1.00 mg/mL at 10, 6 and 2 h incubation periods respectively in a dose dependent manner (P<0.05). An antifilarial effect imparted by plant extract was found to be a function of their relative concentrations. Inhibitory concentration (IC₅₀) for the plant extract was found to be 0.16 mg/mL.ConclusionsThe present study recorded significant antifilarial effect of Vitex negundo plant extract and contributed toward the development of database for novel drug candidates for lymphatic filariasis.     

Biochemical, immunological, and in vivo functional characterization of B-domain-deleted factor VIII

Coagulation factor VIII (FVIII) is a cofactor in the intrinsic pathway of blood coagulation for which deficiency results in the bleeding disorder hemophilia A. FVIII contains a domain structure of A1-A2-B-A3- C1-C2 of which the B domain is dispensable for procoagulant activity in vitro. In this report, we compare the properties of B-domain-deleted FVIII (residues 760 through 1639, designated LA-VIII) to wildtype recombinant FVIII. In transfected Chinese hamster ovary (CHO) cells, LA- VIII was expressed at a 10- to 20-fold greater level compared with wildtype FVIII. The specific activity of purified LA-VIII was indistinguishable from wild-type recombinant FVIII and both exhibited similar thrombin activation coefficients. Wildtype recombinant-derived FVIII and LA-VIII also displayed similar timecourses of thrombin activation and heavy chain cleavage. However, compared with wildtype recombinant-derived FVIII, the light chain of LA-VIII was cleaved fivefold more rapidly by thrombin. Addition of purified von Willebrand factor (vWF) did not alter the kinetics of thrombin cleavage or activation of either wildtype recombinant-derived FVIII or LA-VIII. The immunogenicity of LA-VIII was compared with wildtype FVIII in a novel model of neonatal tolerance induction in mice. The results did not detect any immunologic differences between wildtype FVIII and LA-VIII, suggesting that LA-VIII does not contain significant new epitopes that are absent in wildtype FVIII. LA-VIII was tolerated well on infusion into FVIII-deficient dogs and was able to correct the cuticle bleeding time similar to wildtype recombinant factor VIII. In vivo, LA-VIII was bound to canine vWF and exhibited a half-life similar to wildtype recombinant FVIII. These studies support that B-domain-deleted FVIII may be efficacious in treatment of hemophilia A in humans.     

Stability of Nanocrystalline Spark Plasma Sintered 3Y-TZP

Spark plasma sintered 3Y-TZP has been investigated with respect to hydrothermal ageing and grinding. The sintering was performed between the temperatures of 1,100 and 1,600 °C for a soaking time of 5 minutes and the resulting materials were obtained with grain sizes between 65 to 800 nm and relative densities between 88.5 to 98.8%. Experiments on hydrothermal ageing in water vapour at 131 °C, 2 bars during 60 hours shows that phase stability is retained, elastic modulus and hardness of near surface region measured by nanoindentation does not change in fine grain (<200 nm) materials, in spite of porosity. In ground specimens, very small amount of transformation was found for all grain sizes studied.