Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit.

In this report we demonstrate that proteolytic cleavage of the constituent subunit is one of the causes determining the heterogeneous size distribution of plasma von Willebrand factor (vWf) multimers. As shown by two-dimensional nonreduced/reduced agarose/polyacrylamide gel electrophoresis, the structure of circulating vWf molecules may deviate from that represented by assemblage of a variable number of identical subunits. Indeed, even though the largest multimers in normal plasma appear to be composed predominantly of intact 225-kD subunits, those of intermediate and smaller size contain also 189-, 176-, and 140-kD proteolytic fragments.

Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux.

The effect of a meal on the rate of transient lower esophageal sphincter (LES) relaxations and patterns of gastroesophageal reflux was investigated in 49 patients referred for evaluation of gastroesophageal reflux. Esophageal motility and pH were recorded concurrently before and after a standard meal. In the patients with symptomatic reflux, the meal induced a four- to sevenfold increase in the gastroesophageal reflux through two mechanisms: a four- to fivefold increase in the rate of transient LES relaxations and an increase in the proportion of transient LES relaxations accompanied by reflux from 47% to 68%.

Effect of insulin-induced hypoglycaemia on antral, pyloric and duodenal motility in fasting subjects.

1. Hyperglycaemia alters gastric motility and delays gastric emptying. By contrast, there is little information regarding the effect of sub-normal blood glucose concentrations on gastric and, in particular, pyloric motility, although limited data suggest that hypoglycaemia is associated with accelerated gastric emptying despite an apparently increased basal pyloric pressure.

Independent assembly and secretion of a dimeric adhesive domain of von Willebrand factor containing the glycoprotein Ib-binding site.

von Willebrand factor (vWF) is a multimeric glycoprotein that supports platelet adhesion on thrombogenic surfaces as part of the normal hemostatic response to vascular injury. We have employed a domain-specific expression strategy to analyze the biosynthetic processing steps and minimum structural requirements for assembly of the platelet receptor glycoprotein Ib-binding domain of vWF. A chimeric cDNA that codes for the vWF signal peptide and a segment of vWF internal primary sequence, residues 441-730, directs the secretion of a functional vWF fragment from mammalian cells.

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later.

Role of the proximal and distal stomach in mixed solid and liquid meal emptying.

The role of the proximal and distal stomach in the emptying of solids and liquids from the stomach remains unclear. We have used a dual isotope technique to quantify proximal and distal stomach emptying of a solid (100 g of 99mTc labelled liver/ground beef) liquid (either 200 ml of normal saline (eight subjects) or 25% dextrose (seven subjects) labelled with 113mIn-diethylenetriaminepenta-acetic acid) mixed meal. A manometric catheter simultaneously measured antral, pyloric, and duodenal motor activity.

Monitoring of upper oesophageal sphincter pressure in children.

In children technical limitations of upper oesophageal sphincter manometry have restricted investigation to the pull through technique under sedation. In this study we have used an adapted sleeve manometric technique for upper oesophageal sphincter monitoring in unsedated children and determined the influence of the state of arousal on upper oesophageal sphincter pressure. Twenty six children aged 3 to 42 months (median 17.

Hyperglycaemia stimulates pyloric motility in normal subjects.

The motor correlates of the delay in gastric emptying produced by hyperglycaemia were investigated in 11 healthy volunteers. Fasting gastroduodenal motility was measured during euglycaemia (blood glucose concentration 3-5 mmol/l) and during hyperglycaemia induced by intravenous dextrose (blood glucose concentration 12-16 mmol/l). Antral, pyloric, and proximal duodenal pressures were recorded by a sleeve/sidehole manometric assembly positioned across the pylorus, with the aid of measurements of transmucosal potential difference.

A prospective genetic study of complete and partial hydatidiform moles.

Two hundred two hydatidiform moles were classified by pathologic features and ploidy into partial or complete moles. Further classification was made by using genetic polymorphism, the diagnosis being refined by deoxyribonucleic acid technology. Among 51 partial hydatidiform moles, 44 triploids, two tetraploids, and one diploid were identified.

Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.

von Willebrand factor (vWF) supports platelet adhesion on thrombogenic surfaces by binding to platelet membrane glycoprotein (GP) Ib in the GP Ib-IX receptor complex. This interaction is physiologically regulated so that it does not occur between circulating vWF and platelets but, rather, only at a site of vascular injury. The abnormal vWF found in type IIB von Willebrand disease, however, has a characteristically increased affinity for GP Ib and binds to circulating platelets.

Human anal motility while fasting, after feeding, and during sleep.

The aim of this study was to determine whether the human anal sphincter responds dynamically to changing physiological states. In 19 healthy human subjects, intraluminal anal canal pressure was measured with a 5-cm perfused sleeve sensor during the day while fasting (3 hours) and after feeding (3 hours) and at night during sleep (8 hours). Daytime mean anal canal pressures (+/- SEM) while fasting (50 +/- 3 mm Hg) were similar to those after feeding (49 +/- 3 mm Hg) and to those at night during sleep (49 +/- 3 mm Hg).

Fractures in early childhood: osteogenesis imperfecta or child abuse?

We studied the radiographs of 194 fractures sustained by 39 children less than 5 years of age with osteogenesis imperfecta (OI) and compared them with radiographs of 84 fractures sustained by 69 normal children of the same age. A great variety of fracture patterns was observed in undoubted OI. Spiral and transverse fractures were the most common.

Comparative effects of duodenal and ileal intubation on gastric emptying and postprandial antral, pyloric, and duodenal motility.

The influence of gastric and small-intestinal intubation on fed patterns of antropyloroduodenal motility and gastric emptying of a solid meal has been investigated in normal volunteers. In 10 subjects a manometric assembly was passed as far as the fourth part of the duodenum; in 8 other subjects the terminal ileum was intubated; and a further 8 subjects were not intubated. The manometric assemblies were similar, apart from their length, and both incorporated a sleeve/side hole assembly located across the pylorus.

Sensory nerves of the intestines: role in control of pyloric region of dogs.

The canine pylorus is the target for a large array of extrinsic and intrinsic nerve-produced effects. Some of them have intermediate nicotinic synapses. In all cases observed so far the final nerve terminals mediating excitation are cholinergic, but those mediating inhibition are both adrenergic and non-adrenergic non-cholinergic.

Twitch potentiation during fatiguing exercise in the elderly: the effects of training.

Twitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly.

Current and future drugs for acid-peptic disease: a plethora of opinions on possible mechanisms of action.

Sixty-seven invited participants involved in the development, evaluation, and use of therapies for acid-peptic disorders participated in a meeting to discuss the scientific basis for healing actions of ulcer drugs and the prospects for future developments ("Realities of Mucosal Protection in the Upper Gastrointestinal Tract," Lausanne, Switzerland, November 8-10, 1987). Eighty-one key statements were prepared and subsequently analyzed on the basis of a voting system. Of the 45 statements that dealt with existing therapies, only 3 statements showed positive consensus (agreement of two-thirds or more of voters) about mechanisms of ulcer healing.

Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus.

In 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4-8 mmol/l) and during hyperglycaemia (blood glucose concentration 16-20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised using a modified glucose clamp. Patients were also evaluated for gastrointestinal symptoms, autonomic nerve function and glycaemic control.

Surgery and chemotherapy in the management of placental site tumor.

Since 1977 we have managed seven cases of placental site trophoblastic tumor. All patients were treated with hysterectomy. Three patients had preoperative chemotherapy without evidence of response.

The effect of naloxone on lipid-induced pyloric motor response in humans.

This study examines whether opioid receptors are involved in the mediation of the pyloric motor response to intraduodenal lipid infusion. Antral, pyloric, and duodenal manometry was performed in seven healthy volunteers with a sleeve/multiple side-hole manometric assembly. Triglyceride emulsion and normal saline were infused alternately into the duodenum through the manometric assembly for two 30-minute periods each.

Response of canine lower esophageal sphincter to gastric distension.

The aim of this study was to localize the region of the stomach responsible for triggering distension-induced transient lower esophageal sphincter relaxation (TLESR). The canine stomach was partitioned into subsegments by a row of buttressed sutures. This separated either the fundus from the lesser curve or the proximal stomach from the antrum.

Pathophysiology of gastroesophageal reflux. Lower esophageal sphincter dysfunction in gastroesophageal reflux disease.

LES dysfunction is the principal mechanism responsible for GER disease. Two main patterns of sphincter dysfunction have been identified: an abnormally high rate of transient LES relaxations, and defective basal LES pressure. Overpowering of a weak LES by pressure transients induced by straining is less common than previously thought, at least under conditions tested thus far.