Conformationally restricted analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide

Conformationally restricted analogues of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5; 2) were synthesized. The compounds were tested for muscarinic and antimuscarinic activity in the isolated guinea pig ileum and in intact mice. They were found to be moderately potent muscarinic antagonists or weak partial agonists. The new compounds were less potent than 2 in inhibiting (-)-[3H]-N-methylscopolamine binding in the rate cerebral cortex. Thus, structural modifications of 2 in which part of the amide moiety has been connected with the methyl group in the butynyl chain to form a five-membered ring decrease affinity and in most cases abolish efficacy.     

A comparative evaluation of methods for detecting duodenogastric reflux in patients with peptic ulcer]

The duodenal contents were examined in 81 patients with gastroduodenal ulcer. Bile acid concentrations, alkaline phosphatase activity, and sodium ion concentration were measured for the detection of duodenogastric reflux. Measurements of sodium ion concentration permitted estimation of the immediate volume of the duodenogastric reflux in the gastric contents. No methods for duodenogastric reflux detection should be given preference in examinations of peptic ulcer patients. Multiple-modality studies appear to be the most effective.     

Vestibular testing in comatose patients

The analysis of vestibular responses in a comatose patient often provides the critical information for making a correct preliminary diagnosis and directing the subsequent laboratory evaluation. Because of some uncertainties about what is being tested with the various bedside maneuvers that are used to elicit vestibular responses, we review the physiologic basis for the oculomotor responses that occur with head rotation or with caloric stimuli. We further urge precise and unambiguous terminology to describe both stimulus and response. We suggest using physiologically well-defined terms such as vestibulo-ocular reflex and cervico-ocular reflex and avoiding potentially misleading terms such as the doll's head and the oculocephalic maneuvers.     

Influence of mesh materials on collagen deposition in a rat model.

Alterations of the extracellular matrix (ECM) with its major component collagen are increasingly discussed as possible risk factors implicated in the development of abdominal-wall herniation. Because of the widespread use of alloplastic meshes for the surgical repair of hernias, an animal study was performed to analyze the influence of various mesh materials on the quantity and quality of collagen deposition. In 60 male Sprague-Dawley rats an abdominal replacement was performed using three different kinds of mesh materials: polyester (PE), a pure polypropylene (PP), and a composite mesh made of polypropylene and polyglactin (PG). A simple fascia suture repair served as control. The count of fibroblasts, the collagen/protein ratio, the type I/III collagen ratio, and the expression of basic fibroblast growth factor (b-FGF) at the interface were analyzed after 7, 21, and 90 days. The ratio of collagen to overall protein (microg/mg) showed significant differences comparing different mesh materials (sham controls 38.44 +/- 16.33 microg/mg, PE 68.5 +/- 23.8 microg/mg, PP 101.6 +/- 32.3 microg/mg, PG 49.6 +/- 11.6 microg/mg at day 90). The ratio of collagen type I/III increased over time in all groups. However, 90 days after mesh implantation the ratio was always significantly lowered compared to the controls. No significant difference was found comparing different mesh materials. The alteration of the scar composition is closely connected to an increased b-FGF expression. b-FGF and count of fibroblasts highly correlated (r =.95) and showed significant elevated levels compared to simple suture repair. The results of our study strongly support the notion that wound healing is affected by mesh implantation. The quality of the ECM deposition as determined by collagen type I/III ratio is impaired in general, whereas the quantity of ECM deposition is markedly influenced by the kind of mesh material.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

The effect of oxytocin on basal and pethidine-induced delayed gastric emptying.

1. Continuous infusion of oxytocin (0.33 u min-1) accelerated gastric emptying of semisolid TC-99m labelled Chelex-100 resin/oatmeal in 10 healthy volunteers under basal conditions. 2. Administration of oxytocin did not change the pattern of gastric emptying delayed by pethidine. 3. The emptying pattern of semisolid has confirmed the existence of a lag phase.