bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease
Authors: Forton Daniel M. , Thomas Howard C. , Murphy Christine A. , Allsop Joanna M. , Foster Graham R. , Main Janice , Wesnes Keith A. , Taylor-Robinson Simon D.
Published: August 2002

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P = .02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality.
Critical flicker frequency for quantification of low-grade hepatic encephalopathy
Authors: Kircheis Gerald , Wettstein Matthias , Timmermann Lars , Schnitzler Alfons , Häussinger Dieter
Published: August 2002

Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric tests or neurophysiologic techniques. In view of its sociomedical relevance, simple and reproducible tests for routine diagnosis are required. This study evaluates critical flicker-frequency thresholds for quantification of low-grade hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls) were analyzed for HE severity (mental state, computerized psychometric tests), and the threshold frequencies at which light pulses are perceived as fused (fusion frequency) or flickering light (critical flicker frequency [CFF]). CFF was a highly reproducible parameter with little age, day-time, and training dependency. CFFs in cirrhotic patients without HE (HE 0) were not different from those found in noncirrhotic controls. Significantly lower CFFs were found in cirrhotic patients with subclinical or manifest HE, and the various HE groups separated from each other at a high level of significance (P < .01). By using a CFF cut-off value of 39 Hz, a 100% separation of patients with manifest HE from noncirrhotic controls and HE 0 cirrhotic patients was obtained. SHE patients separated from HE 0 cirrhotic patients with high sensitivity (55%) and specificity (100%). The HE severity-dependent differences were found in both, alcoholic and posthepatitic cirrhosis. Statistically significant correlations (P < .01) were found between CFFs and individual psychometric tests. Aggravation of preexisting HE after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation was accompanied by a corresponding decrease of CFF, whereas improvement of HE increased CFF. In conclusion, CFF is a sensitive, simple, and reliable parameter for quantification of low-grade HE severity in cirrhotic patients and may be useful for the detection and monitoring of SHE.
Interferon and amantadine in naive chronic hepatitis C: A double-blind, randomized, placebo-controlled trial
Authors: Helbling Beat , Stamenic Ivan , Viani Francesco , Gonvers Jean-Jacques , Dufour Jean-Francois , Reichen Jurg , Cathomas Gieri , Steuerwald Michael , Borovicka Jan , Sagmeister Markus , Renner Eberhard L.
Published: August 2002

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 × 100 mg po QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P = .04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P = .05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.
Hepatic encephalopathy—Definition, nomenclature, diagnosis, and quantification: Final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998
Authors: Ferenci Peter , Lockwood Alan , Mullen Kevin , Tarter Ralph , Weissenborn Karin , Blei Andres T.
Published: August 2002

Research on hepatic encephalopathy is hampered by the imprecise definition of this disabling complication of liver disease. Under this light, the Organisation Mondiale de Gastroentérologie commissioned a Working Party to reach a consensus in this area and to present it at the 11th World Congress of Gastroenterology in Vienna (1998). The Working Party continued its work thereafter and now present their final report. In summary, the Working Party has suggested a modification of current nomenclature for clinical diagnosis of hepatic encephalopathy; proposed guidelines for the performance of future clinical trials in hepatic encephalopathy; and felt the need for a large study to redefine neuropsychiatric abnormalities in liver disease, which would allow the diagnosis of minimal (subclinical) encephalopathy to be made on firm statistical grounds. In the interim, it proposes the use of a psychometric hepatic encephalopathy score, based on the result of 5 neuropsychologic tests. Finally, the need for a careful evaluation of the newer neuroimaging modalities for the diagnosis of hepatic encephalopathy was stressed.
Neuropsychological impairment in patients with chronic hepatitis C
Authors: Hilsabeck Robin C. , Perry William , Hassanein Tarek I.
Published: August 2002

Hepatitis C is the most common cause of chronic liver disease in the United States and it significantly reduces quality of life. The role of cognitive deficits contributing to the morbidity of this disease has not been well characterized. The purpose of this study was to examine cognitive functioning in patients with chronic hepatitis C and to investigate relationships among parameters of disease severity and performance on neuropsychological tests. Sixty-six patients with chronic hepatitis C and 14 patients with other chronic liver diseases were administered a brief battery of neuropsychological tests assessing attention, visuoconstructional ability, learning, memory, and psychomotor speed. Cognitive impairment in patients with chronic hepatitis C ranged from 0% on a visuoconstructional task to 82% on a measure of sustained attention and concentration. Test scores of patients with chronic hepatitis C did not differ from those of patients with other chronic liver diseases. Hence, patients with and without chronic hepatitis C experience cognitive deficits, especially in tasks requiring attention and psychomotor speed. In addition, there was a significant relationship between fibrosis stage and test performance, with greater fibrosis associated with poorer performance. However, both patients with and without cirrhosis exhibited cognitive dysfunction. In conclusion, these findings suggest that progressive hepatic injury may result in cognitive problems even before the development of cirrhosis. Future studies need to determine the effect of this decrease in cognitive function on quality of life.
Change in portal flow after liver transplantation: Effect on hepatic arterial resistance indices and role of spleen size
Authors: Bolognesi Massimo , Sacerdoti David , Bombonato Giancarlo , Merkel Carlo , Sartori Giovanni , Merenda Roberto , Nava Valeria , Angeli Paolo , Feltracco Paolo , Gatta Angelo
Published: August 2002

Information on changes in splanchnic hemodynamics after liver transplantation is incomplete. In particular, data on long-term changes are lacking, and the relationship between changes in arterial and portal parameters is still under debate. The effect of liver transplantation on splanchnic hemodynamics was analyzed with echo-Doppler in 41 patients with cirrhosis who were followed for up to 4 years. Doppler parameters were also evaluated in 7 patients transplanted for acute liver failure and in 35 controls. In cirrhotics, portal blood velocity and flow increased immediately after transplantation (from 9.1 ± 3.7 cm/sec to 38.3 ± 14.6 and from 808 ± 479 mL/min to 2,817 ± 1,153, respectively, P < .001). Hepatic arterial resistance index (pulsatility index) also augmented (from 1.36 ± 0.32 to 2.34 ± 1.29, P < .001) and was correlated with portal blood velocity and flow. The early changes in these parameters were related, in agreement with the hepatic buffer response theory. Portal flow returned to normal values after 2 years. Superior mesenteric artery flow normalized after 3 to 6 months. Splenomegaly persisted after 4 years, when spleen size was related to portal blood flow. In 7 patients transplanted for acute liver failure, portal flow, and hepatic arterial resistance index were normal after transplantation. In conclusion, a high portal flow was present in cirrhotics until 2 years after transplantation, probably because of maintenance of elevated splenic flow. An early increase in hepatic arterial resistance indices is a common finding, but it is transient and is related to the increase in portal blood flow. A normal time course of portal-hepatic hemodynamics was detected in patients transplanted for acute liver failure.
Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: A meta-analysis
Authors: Bañares Rafael , Albillos Agustín , Rincón Diego , Alonso Sonia , González Mónica , Ruiz-del-Arbol Luis , Salcedo Magdalena , Molinero Luis-Miguel
Published: August 2002

Endoscopic therapy, involving either injection sclerosis or band ligation, is considered the intervention of first choice for acute variceal bleeding (AVB). Pharmacologic agents have also been shown to be highly effective in the control of the bleeding episode. The purpose of this meta-analysis was to assess whether vasoactive drugs may improve the efficacy of endoscopic therapy (injection sclerosis or band ligation) in the control of AVB and thus increase survival rates. Computer databases and scientific meeting abstracts from 1994 to 2001 were used to search for randomized trials that compared the combined use of endoscopic and drug therapy with endoscopic therapy alone in the control of AVB. Eight trials involving 939 patients fulfilled the selection criteria and the following evaluated by standard meta-analysis methods: initial hemostasis, 5-day hemostasis, 5-day mortality, and adverse events. Combined treatment improved initial control of bleeding (relative risk [RR], 1.12; 95% confidence interval (CI), 1.02-1.23), and 5-day hemostasis (RR, 1.28; 95% CI, 1.18-1.39), with numbers of patients needed to treat (NNT) of 8 and 5, respectively. The difference in favor of combined treatment remained significant when trials that used drugs other than octreotide or that included a low proportion of alcoholic patients (<40%) or high-risk cirrhotic patients (<35%) were excluded. Mortality was not significantly decreased by combined therapy (RR, 0.73; 95% CI, 0.45-1.18). Severe adverse events were similar in both groups. In conclusion, in patients with AVB, pharmacologic agents improve the efficacy of endoscopic therapy to achieve initial control of bleeding and 5-day hemostasis, yet fail to affect mortality.
Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump
Authors: Plass Jacqueline R. M. , Mol Olaf , Heegsma Janette , Geuken Mariska , Faber Klaas Nico , Jansen Peter L. M. , Müller Michael
Published: August 2002

The bile salt export pump (BSEP or ABCB11) mediates the adenosine triphosphate-dependent transport of bile salts across the canalicular membrane of the hepatocyte. Mutations in the corresponding ABCB11 gene cause progressive familial intrahepatic cholestasis type 2. The aim of this study was to investigate the regulation of human ABCB11 gene transcription by bile salts. First, a 1.7-kilobase human ABCB11 promoter region was cloned. Sequence analysis for possible regulatory elements showed a farnesoid X receptor responsive element (FXRE) at position −180. The farnesoid X receptor (FXR) functions as a heterodimer with the retinoid X receptor α (RXRα) and can be activated by the bile salt chenodeoxycholic acid (CDCA). Luciferase reporter gene assays showed that the ABCB11 promoter is positively controlled by FXR, RXRα, and bile salts in a concentration-dependent manner. Mutation of the FXRE strongly represses the FXR-dependent induction. Second, endogenous ABCB11 transcription regulation was studied in HepG2 cells, stably expressing the rat sodium-dependent taurocholate transporter (rNtcp) cells. ABCB11 expression was induced by adding bile salts to the culture medium, and this effect was maximized by combining it with cotransfection of rFxr and hRXRα. Reducing endogenous FXR levels using RNA interference fully repressed the bile salt-induced ABCB11 expression. In conclusion, these results show that FXR is required for the bile salt-dependent transcriptional control of the human ABCB11 gene and that the cellular amount of FXR is critical for the level of activation of ABCB11 transcription.
Hepatitis C virus kinetics during and immediately after liver transplantation
Authors: Garcia-Retortillo Montserrat , Forns Xavier , Feliu Anna , Moitinho Eduardo , Costa Josep , Navasa Miquel , Rimola Antoni , Rodes Juan
Published: August 2002

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope −0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope −0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT. (Hepatology 2002;35:680-687.)
Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties
Authors: Galun Eithan , Eren Rachel , Safadi Rifaat , Ashour Yaffa , Terrault Norah , Keeffe Emmet B. , Matot Edith , Mizrachi Sara , Terkieltaub Dov , Zohar Merav , Lubin Ido , Gopher Judith , Shouval Daniel , Dagan Shlomo
Published: August 2002

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-ABXTL. A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-ABXTL and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-ABXTL induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-ABXTL binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-ABXTL could be combined with other monotherapies that are currently used to treat HBV carriers. (Hepatology 2002;35:673-679.)
Interaction of hepatitis C virus core protein with retinoid X receptor α modulates its transcriptional activity
Authors: Tsutsumi Takeya , Suzuki Tetsuro , Shimoike Takashi , Suzuki Ryosuke , Moriya Kyoji , Shintani Yoshizumi , Fujie Hajime , Matsuura Yoshiharu , Koike Kazuhiko , Miyamura Tatsuo
Published: August 2002

Hepatic steatosis and hepatocellular carcinoma (HCC) are common and serious features of hepatitis C virus (HCV) infection, and the core protein has been shown to play distinct roles in the pathogenesis. Here we report the direct interaction of HCV core protein with retinoid X receptor α (RXRα), a transcriptional regulator that controls many aspects of cell proliferation, differentiation, and lipid metabolism. The core protein binds to the DNA-binding domain of RXRα, leading to increase the DNA binding of RXRα to its responsive element. In addition, RXRα is activated in cells expressing the core protein as well as in the livers of the core-transgenic mice that would develop hepatic steatosis and HCC later in their lives. Using promoter genes of cellular retinol binding protein II (CRBPII) and acyl-CoA oxidase as reporters, we also show that the expression of the core protein enhances the transcriptional activity regulated by the RXRα homodimer as well as by the heterodimer with peroxisome proliferator activated receptor α. Furthermore, expression of the CRBPII gene is also up-regulated in the livers of HCV core-transgenic mice. In conclusion, these results suggest that modulation of RXRα-controlled gene expression via interaction with the core protein contributes to the pathogenesis of HCV infection.
SEN virus: Response to interferon alfa and influence on the severity and treatment response of coexistent hepatitis C
Authors: Umemura Takeji , Alter Harvey J. , Tanaka Eiji , Orii Koji , Yeo Anthony E. T. , Shih Wai-Kuo J. , Matsumoto Akihiro , Yoshizawa Kaname , Kiyosawa Kendo
Published: August 2002

The SEN virus (SENV) is a recently identified single-stranded, circular DNA virus. A strong association between 2 SENV variants (SENV-D and SENV-H) and transfusion-associated non-A-to-E hepatitis has been reported. To clarify the effect of SENV infection on coexisting chronic hepatitis C and the effect of interferon alfa (IFN-α) therapy on SENV replication, SENV DNA was quantitated by polymerase chain reaction in serum samples from 186 patients with chronic hepatitis C. Thirty-nine of 186 (21%) patients with chronic hepatitis C were positive for SENV DNA. There were no differences in the clinical, virologic and histologic features between patients with and without SENV infection. Eighteen of 102 patients with chronic hepatitis C who received IFN-α were positive for SENV DNA. The sustained response rate for hepatitis C virus (HCV) clearance after IFN-α treatment did not differ significantly between patients with SENV (28%) and without SENV infection (39%). SENV DNA levels decreased during therapy in 15 of 16 patients, and 11 of the 16 patients (69%) had a sustained loss of SENV DNA in response to IFN-α. In coinfected patients, SENV responses to IFN-α were significantly better in those who failed to clear HCV RNA than in those who lost HCV RNA (P = .013). In conclusion, SENV infection was frequently found in patients with chronic hepatitis C. SENV infection had no apparent influence on the severity of HCV-related liver disease or the HCV response to IFN-α. SENV was sensitive to IFN-α therapy and the majority of patients had a sustained virologic response.
Arthrodesis of the Equine Proximal Interphalangeal Joint: A Biomechanical Comparison Of Three 4.5‐mm and Two 5.5‐mm Cortical Screws
Authors: Watt Bruce C. , Edwards Ryland B. , Markel Mark D. , McCabe Ron , Wilson David G.
Published: August 2002

Objective— To compare the biomechanical characteristics and mode of failure of 2 parallel‐screw techniques for proximal interphalangeal joint arthrodesis in horses.

Study Design— Randomized block design, blocking for horse (1–5), method of screw fixation (three 4.5‐mm vs two 5.5‐mm), side (left limb vs right limb), and end (front limb vs hind limb). Constructs were loaded to failure in 3‐point bending in a dorsal‐to‐palmar (plantar) direction.

Sample Population— Twenty limbs (10 limb pairs) from 5 equine cadavers.

Methods— A combined aiming device was used to facilitate consistent screw placement. Three parallel 4.5‐mm cortical screws were placed in lag fashion in 1 limb of a pair, and 2 parallel 5.5‐mm cortical screws were placed in lag fashion in the contralateral limb. Arthrodesis constructs were tested in 3‐point bending in a dorsal‐to‐palmar (plantar) direction using a materials‐testing machine. Loading rate was 19 mm/s. Maximal bending moment at failure and composite stiffness were obtained from bending moment—angular deformation curves. Data were analyzed using ANOVA and χ2 analysis.

Results— There were no significant differences in bending moment (P > .05, power = 0.8 @δ= 19%) or composite stiffness (P > .05, power = 0.8 @δ= 19%) between the 2 fixation techniques. Higher maximal bending moment was found in front limbs than hind limbs, and front limbs with two 5.5‐mm screws than hind limbs with two 5.5‐mm screws. In all cases, constructs completely failed. A greater number of 4.5‐mm cortical screws failed than 5.5‐mm cortical screws.

Conclusions— In pastern arthrodesis constructs loaded in 3‐point bending, end (front limb vs hind limb) affected maximal bending moment at failure of constructs. There was no significant effect of horse, treatment, or side on maximal bending moment or stiffness. Two 5.5‐mm cortical screws should provide a surgically simpler pastern arthrodesis than three 4.5‐mm cortical screws while maintaining similar biomechanical characteristics.

Clinical Relevance— Three 4.5‐mm screws or two 5.5‐mm screws will provide similar biomechanical characteristics in bending when performing equine pastern arthrodesis.
Extra‐articular absorbable suture stabilization of coxofemoral luxation in dogs
Authors: Martini Filippo Maria , Simonazzi Barbara , Del Bue Maurizio
Published: August 2002

Objective—To evaluate the effectiveness of an extra‐articular surgical technique using absorbable suture material for the stabilization of traumatic coxofemoral luxation in dogs.

Study Design—Prospective, clinical study.

Animals—Fourteen client‐owned dogs with recent and long‐standing traumatic coxofemoral luxation (13 craniodorsal and 1 ventral).

Methods—Coxofemoral luxations were surgically reduced and maintained in place with an extra‐articular iliofemoral multifilamentous absorbable suture (3 to 6 strands of 2 USP Polyglactin 910). No external support was employed, and all the dogs were encouraged to use the affected limb postoperatively. The average time of clinical and radiographic follow‐up was 11.6 ± 6.3 months (from 2 to 22 months).

Results—During the follow‐up period, no reluxations occurred and no complications associated with the surgical technique were identified. The dogs started bearing weight from 1 to 10 days after the surgery (mean, 4.3 ± 2.9 days) and the period of lameness ranged from 7 to 30 days (20 ± 8.6 days). At the final clinical examination, the dogs did not demonstrate any lameness or pain during passive flexo‐extension movements, and there was no significant limitation of the range of motion.

Conclusions—Extra‐articular stabilization with multifilamentous absorbable sutures is a simple, effective method of treatment for acute and chronic coxofemoral luxation. The absorbable material used is strong enough to maintain articular stability during the period of scar tissue formation even in large‐breed dogs.

Clinical Relevance—Absorbable sutures avoid the possible complications related to the use of nonabsorbable material and seem to be sufficient to maintain articular stability during the capsular healing process.
Controlling halo‐chaos via wavelet‐based feedback
Authors: Fang Jin-Qing , Chen Guanrong , Zhao Geng
Published: August 2002

Halo‐chaos in high‐current accelerator has become one of the key issues because it can cause excessive radioactivity from the accelerators and significantly limits the applications of the new accelerators in industrial and other fields. Some general engineering methods for chaos control have been developed, but they generally are unsuccessful for halo‐chaos suppression due to many technical constraints. In this article, controllability condition for beam halo‐chaos is analyzed qualitatively. Then Particles‐in‐Cell (PIC) simulations explore the nature of beam halo‐chaos formation. A nonlinear control method and wavelet function feedback controller are proposed for controlling beam halo‐chaos. After control of beam halo‐chaos for initial proton beam with water bag distributions, the beam halo strength factor H
is reduced to zero, and other statistical physical quantities of beam halo‐chaos are doubly reduced. The results show that the developed methods in this paper are very effective for proton beam halo‐chaos suppression. Potential application of the halo‐chaos control method is finally pointed out.
A Noise‐shaping Accelerometer Interface Circuit for Two‐chip Implementation
Authors: Kajita Tetsuya , Moon Un-Ku , Temes Gabor C.
Published: August 2002

This paper introduces a new architecture for sensor interface circuits using a delta–sigma modulator. The three‐level force feedback allows the use of a digital compensator to stabilize the loop. A 3rd‐order delta–sigma structure shapes the op‐amp noise and allows a two‐chip implementation with high loop gain at low frequencies.
Determining the gel point of an epoxy resin by various theological methods
Authors: Halley P J , Mackay M E , George G A
Published: August 2002

The gel point of TGDDM-based epoxy resin MY721 (Ciba Geigy) mixed with DDS (Sigma) was determined using multiwave, dynamic-time and steady-time tests. The gel times from each test agreed within experimental variations and the effects of temperature, sample size and shear rate are discussed. New methods of determining the gel point of thermosetting resins are discussed using multiwave tests and normal stress measurements during steady shear tests.
A dynamical model of Jupiter's auroral electrojet
Authors: Achilleos N , Miller S , Prangé R , Millward G , Dougherty M K
Published: August 2002

A global simulation for the auroral electrojet on Jupiter is presented. The required sequence of models was computed using JIM (the Jovian Ionospheric Model), a time-dependent, three-dimensional model for the thermosphere and ionosphere of Jupiter, and ana priorimodel for the planet's ionospheric electric field. We describe the plasma dynamics in the model by considering ion and electron motions at pressure levels less than 2 µbar, lying above Jupiter's dynamo region, and including the region of maximum energy deposition by auroral particles.

By considering the motions of the neutral species being `dragged' by the electrojet, we quantify the electrodynamic coupling between the neutral thermosphere and the auroral ionosphere. Two distinct altitude regions evolve in the model simulations, distinguished by different thermospheric flow patterns. Higher-altitude regions are subject to gas dynamic flow, while lower-altitude regions are strongly influenced by electrodynamic flow, associated with the transfer of momentum from the electrojet to the neutral gas. The electrojet models provide a basis for physical interpretation of current observational detections of ion motions in the Jovian auroral regions; as well as a means of optimizing future observations, in order to make similar detections.
On the search for neutrino oscillations using an artificial neutrino source
Authors: Barabanov I R , Belli P , Bernabei R , Dai C J , Gurentsov V , Incicchitti A , Kornoukhov V , Yanovich E
Published: August 2002

In this paper the possibility of searching for neutrino oscillations with an artificial neutrino source is discussed and a comparison with reactor experiments is carried out.
Prenatal testosterone treatment potentiates the aggression‐inhibiting effect of the neurosteroid dehydroepiandrosterone in female mice
Authors: Perché Fabrice , Young Jacques , Robel Paul , Simon Neal G. , Haug Marc
Published: August 2002

The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 μg/d) on aggression in female offspring where dams were treated with 1, 10, or 100 μg of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100‐μg prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100‐μg T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130–138, 2001. © 2001 Wiley‐Liss, Inc.
Effective Teaching of Adults: Themes and Conclusions
Authors: Ross‐Gordon Jovita M.
Published: August 2002

The discussion examines several key themes emerging across the chapters: multiple perspectives on teaching adults, reflecting on beliefs and practices, and transforming teaching practices.
Predicting a moving object position for visual servoing: theory and experiments
Authors: Gortcheva E. , Garrido R. , González E. , Carvallo A.
Published: August 2002

In order to perform visual servoing tasks in a robotic system, one is confronted with the low sampling rate of standard cameras and the time delay introduced by image processing. One way to circumvent the time‐delay problem is to estimate future positions of the moving object of interest employing prediction techniques. In this work, three prediction techniques, namely Kalman filtering and two adaptive techniques employing least squares with forgetting factor and the projection algorithm, respectively, are evaluated in terms of their prediction error. Experimental results show that the adaptive techniques give best results and the Kalman filter‐based predictor shows a high sensitivity to velocity changes of the moving object. Copyright © 2001 John Wiley & Sons, Ltd.
Soluble angiogenic factors: Implications for chronic myeloproliferative disorders
Authors: Musolino C. , Calabro' L. , Bellomo G. , Martello F. , Loteta B. , Pezzano C. , Rizzo V. , Alonci A.
Published: August 2002

The role of angiogenesis for the progressive growth and metastatic process of tumours is well established. What is not clear, though, is the clinical prognostic significance of the angiogenic factors in malignant haematological diseases. In this study, we have assessed the plasma and serum levels of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b‐FGF) in 55 patients affected by chronic myeloproliferative disorders (CMD). This series included 25 patients with essential thrombocythemia (ET), 10 patients with chronic myelocytic leukaemia (CML), 14 patients with polycythemia vera (PV), and 6 patients with primary myelofibrosis (MF), and they were compared to 20 healthy control subjects. In all patients the plasma VEGF concentration was significantly increased to the healthy control group (P < 0.004). The highest concentrations were found in the patients with ET (178.25 ± 125.22 pg/ml). The VEGF levels were significantly higher in CMD patients with vascular complications than those in CMD patients without complications (P < 0.01). The b‐FGF serum levels also appeared to be significantly higher in almost all the CMD patients compared to the control group (P < 0.07). A significant correlation was found between the VEGF levels and the platelet count in the ET patients and the spleen index in the CML patients. VEGF level, in this study, is associated with increased risk of thrombotic complications. There is evidence of increased levels of soluble angiogenic factors in malignant haematological disorders, but their contribution to the progression of diseases is yet unclear. Am. J. Hematol. 69:159–163, 2002. © 2002 Wiley‐Liss, Inc.
Inverse relationship between plasma von Willebrand factor and soluble P selectin in patients with type 1 but not type 2 von Willebrand disease
Authors: Blann A.D. , Nitu‐Whalley I.C. , Lee C.A. , Lip G.Y.H.
Published: August 2002

P selectin is a component of endothelial Wiebel‐Palade body membrane and platelet alpha granule membrane. Patients with von Willebrand disease (VWD) have low plasma von Willebrand factor (VWF). To examine the relationship between plasma P selectin and VWF, both were measured by ELISA in 38 patients with VWD and 40 controls. The patient had lower VWF (P < 0.001) but similar P selectin levels (P = 0.458). In 24 type 1 VWD patients, VWF and P selectin correlated inversely (P = 0.005) but in 14 type 2 VWD patients there was no correlation (P = 0.997). These data imply major differences in VWF/P‐selectin regulation between types 1 and 2 VWD. Am. J. Hematol. 69:135–137, 2002.© 2002 Wiley‐Liss, Inc.
Burkitt's lymphoma of stomach: A case report and review of literature
Authors: Sharma Atul , Raina Vinod , Gujral Sumeet , Kumar Rajive , Tandon Rakesh , Jain Paresh
Published: August 2002

Primary gastrointestinal non‐Hodgkin's lymphoma is a distinct clinicopathological entity. This is the commonest site of all extranodal lymphomas. Non‐endemic Burkitt's lymphoma (high‐grade, small non‐cleaved lymphocytic type) is rare in non‐HIV adult population. We hereby report Burkitt's lymphoma of stomach in a non‐HIV adult. Gastric and lymph node biopsy confirmed the diagnosis. Patient was treated using a third generation chemotherapy protocol without any surgical resection. The patient relapsed within 3 months of completion of primary treatment and died of progressive disease. Am. J. Hematol. 67:48–50, 2001. © 2001 Wiley‐Liss, Inc.
Malignant mesothelioma in Australia, 1945–2000*
Authors: Leigh James , Davidson Patricia , Hendrie Leigh , Berry Dale
Published: August 2002

Background

Australia has maintained a total national malignant mesothelioma case register since 1980. There has been a marked increase in the incidence of mesothelioma in the last 20 years. Currently 450–600 cases are notified annually in a population of 20 million. While the history of the Wittenoom (Western Australia) crocidolite mine and its aftermath is well known, these cases comprise only 5% of the total. This study describes the incidence of mesothelioma in Australia from 1945 to 2000.

Methods

Using register data, time trends in mesothelioma incidence were calculated. Analyses of incidence are reported by age, sex, anatomical site, and state of notification. Associations with occupational and environmental asbestos exposure histories are described. Lung fiber content measurements were made on a subset of cases.

Results

Australia has had 6,329 cases of mesothelioma from 1 January 1945 to 31 December 2000. (A further 620 cases were notified in the period from 1 January 2001 to 31 October 2001.) Annual incidence rates for Australia per million population ≥ 20 years (1997) were: male, 59.8; female, 10.9; total, 35.4. Incidence rates have been continually increasing and are the highest reported national rates in the world. While Western Australia has the highest rate (1997 total rate, 52.8), most cases arise from the two most populous eastern states, New South Wales and Victoria. In 88% (male 90%, female 61%) of cases, a history of asbestos exposure was obtained. Exposures occurred in a wide variety of occupational and environmental circumstances. In 80% of cases with no history of exposure, TEM lung asbestos fiber counts > 200,000 fibers > 2 μm length per gm dry lung were obtained, suggesting unrecognized exposure.

Conclusions

Australia's high incidence of mesothelioma is related to high past asbestos use, of all fiber types, in a wide variety of occupational and environmental settings. The number of cases in total is expected to be about 18,000 by 2020, with about 11,000 yet to appear. Am. J. Ind. Med. 41:188–201, 2002. © 2002 Wiley‐Liss, Inc.
Re: Malignant mesothelioma from neighborhood exposure to anthophyllite asbestos
Authors: Kottek Michael , Kilpatrick David
Published: August 2002

We read with interest the recent case report of mesothelioma associated with neighborhood exposure to anthophyllite asbestos [Rom et al., 2001], and a report of asbestosis from occult exposure to anthophyllite [Dodson and Levin, 2001]. However, we wish to correct Rom's assertion that anthophyllite was mined exclusively in Finland and Japan. Five hundred and ten tons of anthophyllite was mined in the Bindi Bindi area of Western Australia during the period 1942‐49 [Carter and Lipple, 1982]. The mining was largely open cast and the resulting ore was transported by railway to Perth, the capital city of Western Australia. The ore was then milled in a predominantly suburban area. The majority of the fiber produced was exported to unknown destinations, although some was used locally for boiler lagging, acid resistant filters and oil filters [Johnson, 1948]. It is not known what, if any, dust extraction system was in place at the mill. The current condition of the mine site is not known. However, the area surrounding the mine site was and remains a sparsely populated area and only a small population would be affected by any continuing environmental exposure.
Prader Willi/Angelman and DiGeorge/velocardiofacial syndrome deletions: Diagnosis by primed in situ labeling (PRINS)
Authors: Tharapel Avirachan T. , Kadandale Jayarama S. , Martens Paula R. , Wachtel Stephen S. , Wilroy R. Sid
Published: August 2002

A recently developed methodology—primed in situ labeling (PRINS)—can be used in place of fluorescence in situ hybridization (FISH) to diagnose microdeletions. To demonstrate the efficiency, sensitivity, and specificity of PRINS in the diagnosis of microdeletions, we studied groups of patients with Prader Willi/Angelman (PWS/AS) syndrome and DiGeorge/velocardiofacial syndrome (DGS/VCFS). Results obtained by PRINS were then confirmed with the results obtained with FISH. Oligonucleotide primers specific for SNRPN and GABRB3 were used for PWS/AS syndromes. For DGS/VCFS, the primers used were DGCR2/TUPLE1 loci. Labeling patterns obtained by PRINS and FISH were analyzed and scored under a fluorescence microscope. Five normal subjects served as controls and were used for standardization of the PRINS protocol. In all, 20 study patients were involved: 10 PWS/AS and 10 DGS/VCFS. Five of the 10 patients referred with the clinical diagnosis of PWS/AS showed absence of labeling for SNRPN and GABRB3 on one chromosome 15, confirming deletion of the two loci. Similarly, 6 of the 10 patients referred for DGS/VCFS showed deletion for the DGCR2/TUPLE1 loci on one chromosome 22. The remaining patients and controls had normal patterns for all the loci as indicated by FISH and PRINS. Concordant FISH and PRINS results were obtained in all patients and controls studied. © 2001 Wiley‐Liss, Inc.
Application of robust pedigree analysis in studies of complex genotype–phenotype relationships in fragile X syndrome
Authors: Loesch D.Z. , Huggins R.M. , Taylor A.K.
Published: August 2002

Relationships between the fragile X dynamic mutation and palmar and finger epidermal ridge measures were assessed using a robust modification of the maximum likelihood estimators for pedigree data. A total of 34 extended families affected with fragile X syndrome were used. Phenotypic traits included ridge count on the thumb and ridge breadth measured in the second palmar interdigital area bilaterally. Genotypic measures were represented by the number of CGG repeats in the FMR1 gene, the levels of specific FMR1 protein (FMRP), fragile X category defined by the size of the CCG repeat, and methylation status of the gene. The results demonstrated a significant fragile X effect (related to the number of CGG repeats) in the thumb ridge count in males. This effect was more evident in ridge breadth and was found in both sexes. However, the relationship between both phenotypic traits and the level of FMRP was nonsignificant. The study makes a useful contribution to the development of methodologies for the analysis of genotype–phenotype relationships in dynamic mutations, especially in overcoming extensive variability in both the genotype and phenotype, and in approaching the statistical problems related to intergenerational changes in repeat size. The findings support the hypothesis that the fragile X mutation affects limb development during an early fetal period. © 2001 Wiley‐Liss, Inc.
Possible association of NTDs with a polyhistidine tract polymorphism in the ZIC2 gene
Authors: Brown Lúcia Y. , Hodge Susan E. , Johnson William G. , Guy Sandra G. , Nye Jeffrey S. , Brown Stephen
Published: August 2002

Neural tube defects (NTDs) and brain malformations represent a common finding in chromosome 13q deletion patients. Hemizygosity for ZIC2, which is located in the 13q32 critical deletion region, results in holoprosencephaly (HPE) in humans, and diminished expression of ZIC2 results in HPE as well as lumbosacral NTDs in mice. Taken together, these observations led us to hypothesize that ZIC2 mutations may be a cause of isolated NTD. To test this, we screened 192 NTD patients for mutations in ZIC2. While we did not find ZIC2 mutations in these patients, we did find some evidence of a possible association between a histidine tract polymorphism in ZIC2 and NTDs. Our sample was too small to reach definitive conclusions, but the evidence is sufficiently intriguing to encourage further research. If this association is confirmed, subtle alterations in ZIC2 activity may confer a risk of NTD. © 2002 Wiley‐Liss, Inc.
Girl with combined cellular immunodeficiency, pancytopenia, malformations, deletion 11q23.3 → qter, and trisomy 8q24.3 → qter
Authors: Õunap Katrin , Bartsch Oliver , Uibo Oivi , Laidre Piret
Published: August 2002

We describe here a 3‐year‐old girl demonstrating combined cellular immunodeficiency of B‐ and T‐cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3‐qter and trisomy 8q24.3‐qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one‐third to one‐half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23‐q24 region. Our case narrows down the critical interval for thrombo‐ or pancytopenia to 11q23.3‐q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24‐q25 and/or the ETS‐1 proto‐oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B‐ and T‐lymphocytes) in our patient. © 2002 Wiley‐Liss, Inc.
Duodeno‐jejunal atresia with volvulus, absent dorsal mesentery, and absent superior mesenteric artery: A hereditary compound structure in duodenal atresia?
Authors: Pumberger W. , Birnbacher R. , Pomberger G. , Deutinger J.
Published: August 2002

Duodenal atresia predominantly represents an isolated entity, but could also be part of a complexly structured intestinal malformation. We report four children, including two from one family, with duodeno‐jejunal atresia associated with malrotation, volvulus, and absent parietal attachment of the mesentery. Gross absence of the mesentery and absence of distal parts of the superior mesenteric artery were the most remarkable findings. The small intestine was supplied retrogradely from the right colic artery. Consideration of embryological theories of this malformation takes into account the important role of the duodeno‐jejunal flexure during the process of entry of the small bowel loops into the abdomen. Familial occurrence suggests autosomal recessive inheritance. We propose differentiating the pathoanatomical findings in our patients from classical apple peel small bowel syndrome (APSB). © 2002 Wiley‐Liss, Inc.