Summary
Introduction : Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated.
Aims : ...To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose–response relationship.
Patients and methods : In an open 12‐month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise ≥ 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention.
Results : Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017).
Conclusions : Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.
X-shooter is the first 2nd generation instrument of the ESO Very Large Telescope (VLT). It is a very efficient, single-target, intermediate-resolution spectrograph that was installed at the ...Cassegrain focus of UT2 in 2009. The instrument covers, in a single exposure, the spectral range from 300 to 2500 nm. It is designed to maximize the sensitivity in this spectral range through dichroic splitting in three arms with optimized optics, coatings, dispersive elements and detectors. It operates at intermediate spectral resolution (R ~ 4000−17 000, depending on wavelength and slit width) with fixed échelle spectral format (prism cross-dispersers) in the three arms. It includes a 1.8″ × 4″ integral field unit as an alternative to the 11′′ long slits. A dedicated data reduction package delivers fully calibrated two-dimensional and extracted spectra over the full wavelength range. We describe the main characteristics of the instrument and present its performance as measured during commissioning, science verification and the first months of science operations.
To investigate the emptying of enzyme granules and dietary lipids in patients with pancreatic insufficiency secondary to chronic pancreatitis.
Seven patients with chronic pancreatitis and exocrine ...pancreatic insufficiency ingested a test meal including colloidal 99m-technetium-radiolabelled liver paté, and swallowed two pancreatin capsules, in which half of the granules had been replaced with 111-indium-radiolabelled plastic particles of comparable physical dimensions. The passage of the two isotopes was followed simultaneously by gamma camera imaging for direct visual judgement and calculation of mean gastric emptying time.
Pancreatin granules and dietary lipids were observed to empty simultaneously. In the duodenum the particles and the test meal were well mixed. Mean gastric emptying time of radiolabelled liver paté and radiolabelled plastic particles could be calculated in six patients. The median of these values were 47 and 43 min, respectively (P = 0.69).
Pancreatin granules sized 1.0-1.5 mm seem to empty together with dietary lipids.
Background & Aims: Undernourished patients have an increased risk of complications and a prolonged hospital stay, compared to those who are not undernourished. The aim of this study was to evaluate ...the effect of nutritional intervention in a random sample of hospitalized patients at nutritional risk.
Methods: A randomized, controlled trial of nutritional intervention in 212 patients. Intervention consisted of a specialized nutritional team (nurse and dietician) who attended patients and staff for motivation, detailed a nutritional plan, assured delivery of prescribed food and gave advice on enteral or parenteral nutrition when appropriate. The control group received the standard regime used in the department. The primary endpoint was the part of the length of stay (LOS) that was considered to be sensitive to nutritional support, designated LOS
NDI. The nutritional discharge index (NDI) consists of three objective criteria: (1) the patient is able to manage toilet visits without assistance, reflecting mobilization; (2) the patient is without fever (tp<38°C), reflecting absence of infection; and (3) the patient has no intravenous access, reflecting absence of complications in general. On the day when all three criteria were fulfilled, hospital stay was no longer considered to be sensitive to nutritional support. Actual LOS is also reported. Incidence and severity of complications were recorded to explain LOS
NDI findings. As a secondary endpoint, quality of life was evaluated by the Short Form 36 (SF-36) questionnaire.
Results: Intervention led to an intake of ⩾75% of requirements in 62% of the intervention patients, as compared to 36% of the control patients. Rates of complications, mean LOS
NDI and LOS were not significantly different between the two study groups. However, among patients with complications a difference in LOS
NDI between intervention patients (14±2 days, mean±SE) and control patients (20±2 days) was statistically significant (
P=0.015). In the same patients, LOS was 17±2 days in the intervention group and 22±2 days in the control group (
P=0.028). The SF-36 questionnaire did not show a significant effect of treatment.
Conclusions: Protein and energy intake of nutritionally at-risk patients was increased which resulted in shortening of the part of the length of stay that was considered to be sensitive to nutritional support (LOS
NDI) and shorter length of stay (LOS) among patients with complications.
Melanin concentrating hormone (MCH) is a regulator of ingestive behavior, but several issues regarding its effects on specific components of ingestive behavior remain to be elucidated. Therefore, we ...injected, in the 3rd ventricle of male Wistar rats, saline, MCH (5 μg), MCH (5 μg) together with a MCH1-R antagonist (A, 10 μg) and the antagonist alone (A, 10 μg). Our results show that (1) central administration of MCH stimulates food intake (lab chow and medium high fat diet) and this can be blocked by a MCH1-R antagonist; (2) the MCH-induced increase in food intake is mediated through increased meal number, meal duration and meal size; (3) the MCH1-R antagonist is able to significantly reduce the intake of a highly palatable food (condensed sweet milk) and is more effective in blocking MCH-induced food intake when rats are fed a palatable medium high fat food; and (4) MCH stimulated water intake independently from and disproportionately to food intake. In conclusion, our results point to an involvement of endogenous MCH in the enhanced intake of palatable food. Furthermore, they confirm that MCH stimulates not only food intake but also water intake.
Our purpose was to examine gastric lipase secretion after cephalic stimulation (sham feeding) and to examine the effect of cholinergic blockade. Eight healthy volunteers, four women and four men, age ...21-58 years, were studied twice on separate days. They were sham fed with and without infusion of atropine. Gastric content was measured and the amount as well as the activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin (CCK) were measured simultaneously by radioimmunoassays. Cephalic stimuli can evoke human gastric lipase secretion, and this effect was almost ablated by atropine blockade of cholinergic receptors. The concentrations of CCK and secretin in plasma were unaffected by sham feeding with or without atropine blockade, whereas gastrin was stimulated by sham feeding after atropine blockade. Gastric lipase secretion in man is apparently controlled by interacting vagal and hormonal mechanisms.
Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCH1R) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of ...benzamide antagonists. The structure−activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. While these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxyphenoxyacetamide western appendage provided a favorable combination of activity and solubility properties. The amine in the eastern appendage, originally required by the pharmacophore model and believed to interact with Asp123 in transmembrane 3 of MCH1R, could be removed without diminishing affinity or functional activity of the compounds. Docking studies suggested that the Asp123 interacts preferentially with the nitrogen of the central quinoline. Synthesis and testing of specific analogues supported our revised binding mode hypothesis.
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