252 research outputs found
H3-receptor regulation of vascular gastrin and somatostatin releases by the isolated rat stomach.
We have studied the effects of the H3-receptor agonist (R) alpha-methylhistamine [(R) alpha-MeHA] and the H3-receptor antagonist thioperamide (Thiop) on basal- and carbachol-stimulated vascular gastrin release (GR) and somatostatin release (SR) by the isolated rat stomach. Carbachol dose-dependently stimulated and inhibited GR and SR, respectively. Maximal stimulation of GR (500 +/- 112 percent of basal; p < .01), and maximal inhibition of SR (-62 +/- 9 percent under basal; p < .01) were obtained with 1 micron carbachol. Neither (R)alpha-MeHA nor Thiop, up to 10 microns, affected GR. However, SR was dose-dependently enhanced by Thiop (25 +/- 8 percent for 10 microns). Carbachol stimulation of GR was strongly inhibited by Thiop (30 +/- 7 percent for 100 nM and 73 +/- 14 percent for 1 microgram), whereas it was potentiated by (R)alpha-MeHA. Carbachol inhibition of SR was reversed by Thiop and (R)alpha-MeHA. However, the reversal effect of (R)alpha-MeHA was prevented by the CCKB/gastrin receptor antagonist PD134308. These results support H3-receptor regulation of basal and cholinergically-stimulated GR and SR
Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust Study
Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response.
Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 mu g/kg/wk) and weight. based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment.
Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91(41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3).
Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice. (Ada gastroenterol. belg., 2010, 73, 5-11)
Is there an integrative center in the vertebrate brain-stem? A robotic evaluation of a model of the reticular formation viewed as an action selection device
Neurobehavioral data from intact, decerebrate, and neonatal rats, suggests that the reticular formation provides
a brainstem substrate for action selection in the vertebrate central nervous system. In this article, Kilmer,
McCulloch and Blum’s (1969, 1997) landmark reticular formation model is described and re-evaluated, both in
simulation and, for the first time, as a mobile robot controller. Particular model configurations are found to
provide effective action selection mechanisms in a robot survival task using either simulated or physical robots.
The model’s competence is dependent on the organization of afferents from model sensory systems, and a genetic
algorithm search identified a class of afferent configurations which have long survival times. The results support
our proposal that the reticular formation evolved to provide effective arbitration between innate behaviors
and, with the forebrain basal ganglia, may constitute the integrative, ’centrencephalic’ core of vertebrate brain
architecture. Additionally, the results demonstrate that the Kilmer et al. model provides an alternative form of
robot controller to those usually considered in the adaptive behavior literature
Effectiveness and tolerability of pegylated interferon alfa2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study
Background and study aims : Large international clinical trials
conducted in the past 5 years rapidly improved the treatment of chronic
hepatitis C; however, it is unclear whether the advances seen in clinical
trials are being paralleled by similar improvements in routine clinical
practice. PegIntrust is a Belgian community based trial evaluating
the sustained virological response.
Patients and Methods : Observational study of 219 patients
receiving pegylated interferon alfa-2b (1.5 μg/kg/wk) and weight-based
ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point
was sustained virological response (SVR), defined as undetectable
HCV RNA 6 months after the completion of treatment.
Results : In total, 108 patients (49.3 %) had undetectable HCV
RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111
patients without an end-of-treatment response, 28 were non-responders,
and 21 had virological breakthrough. In total, 134 patients
attained early virological response (EVR); 88 (65.7%) of those patients
attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not
attain EVR also did not attain SVR. Age, fibrosis score and baseline
viral load were identified as important predictors of treatment outcome.
The most frequently reported serious adverse events resulting in treatment
discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n
= 6) and fever (n = 3).
Conclusion : Our data indicate that treatment of chronic hepatitis C
with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable
treatment outcomes in a Belgian cohort of patients treated in community-
based clinical practice
Hepatitis C of genotype 2: the role of medical invasive exams.
BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of frequency in Belgium. The aim of this study was to better define the genotype 2 carriers' epidemiology characteristics. METHODS: In a database comprising 1726 viremic hepatitis C virus patient from the south part of Belgium, the files of 98 genotype 2 carriers were reviewed. RESULTS: There was a strong association between genotype 2 and the mode of transmission. The rate of contamination by invasive medical exams was very high (23%), and statistically different from the one of the others genotypes. Eligibility for antiviral therapies and the rate of sustained viral response were high. CONCLUSION: HCV genotype 2 was highly associated with transmission by invasive medical exams.Peer reviewe
Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort
BACKGROUND:
Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.
METHODS:
A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.
RESULTS:
SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655.
CONCLUSIONS:
In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin
HCV genotype distribution in Flanders and Brussels (Belgium): unravelling the spread of an uncommon HCV genotype 5a cluster
Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique
<p>Abstract</p> <p>Background</p> <p>Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components.</p> <p>Methods</p> <p>A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed.</p> <p>Results</p> <p>Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine.</p> <p>Conclusions</p> <p>Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.</p
Intensive enteral nutrition is ineffective for individuals with severe alcoholic hepatitis treated with corticosteroids.
peer reviewedBACKGROUND & AIMS: Severe alcoholic hepatitis (AH) is a lifethreatening
disease for which adequate oral nutritional support
is recommended. We performed a randomized controlled trial to
determine whether the combination of corticosteroid and
intensive enteral nutrition therapy is more effective than corticosteroid
therapy alone in patients with severe AH. METHODS:
We enrolled 136 heavy consumers of alcohol (age, 18–75 y)
with recent onset of jaundice and biopsy-proven severe AH in
our study, performed at 18 hospitals in Belgium and 2 in
France, from February 2010 through February 2013. Subjects
were assigned randomly (1:1) to groups that received either
intensive enteral nutrition plus methylprednisolone or conventional
nutrition plus methylprednisolone (controls). In the
intensive enteral nutrition group, enteral nutrition was given
via feeding tube for 14 days. The primary end point was patient
survival for 6 months. RESULTS: In an intention-to-treat analysis,
we found no significant difference between groups in
6-month cumulative mortality: 44.4% of patients died in the
intensive enteral nutrition group (95% confidence interval [CI],
32.2%–55.9%) and 52.1% of controls died (95% CI, 39.4%–
63.4%) (P ¼ .406). The enteral feeding tube was withdrawn
prematurely from 48.5% of patients, and serious adverse
events considered to be related to enteral nutrition occurred in
5 patients. Regardless of group, a greater proportion of patients
with a daily calorie intake less than 21.5 kcal/kg/day died
(65.8%; 95% CI, 48.8–78.4) than patients with a higher intake
of calories (33.1%; 95% CI, 23.1%–43.4%) (P < .001).
CONCLUSIONS: In a randomized trial of patients with severe AH
treated with corticosteroids, we found that intensive enteral
nutrition was difficult to implement and did not increase survival.
However, low daily energy intake was associated with greater
mortality, so adequate nutritional intake should be a main goal for
treatment
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