PubMed HealthSearch

Biomedical subjects

R C Heading

Publications and source records attributed to R C Heading.

At least 19 recordsLinked to original sources

Site and mechanism of pain perception with oesophageal balloon distension and intravenous edrophonium in patients with oesophageal chest pain.

Ten healthy volunteers and 13 patients with oesophageal motility disorders whose primary presenting complaint was chest pain were studied by distending an intraoesophageal balloon in 1 ml steps to the point of a sensation of discomfort. The net balloon pressure (intra-balloon pressure when inflated within the oesophagus minus the pressure recorded at the same volume outside the patient) was measured at each volume increment and the distension volume at the perception of discomfort was noted. The measurements were repeated after intravenous injection of edrophonium (80 micrograms/kg) and again after 1.2 mg intravenous atropine. Oesophageal wall compliance was similar in patients and controls, and the two groups showed a similar effect of decreased compliance with edrophonium and increased compliance after atropine. There were no significant differences between patients and controls of distending volume at perception of discomfort. Edrophonium, however, resulted in a significant reduction in distension threshold for pain (p less than 0.03) in patients. A similar though non-significant trend was seen in controls. In both controls and patients, distension volume for pain production after atropine was significantly (p less than 0.01) higher than after edrophonium. From these results and other published data, we suggest that the pain receptor for noxious stretch and after edrophonium challenge is likely to be an 'in series' mechanoreceptor located in oesophageal longitudinal muscle.

Adult

Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh.

With the increasing availability of manometry, patients with achalasia are often referred at an early stage when they lack the classic features of established disease. A prospective five year study of the presenting features of untreated achalasia referred to our department was undertaken. Twenty men and 18 women presented throughout adult life, with a mean age at the time of diagnosis of 44 years (range 17 to 76 years). The presenting symptoms were dysphagia: for solids (100%) and for liquids (97%), chest pain (74%), and weight loss (60%). Endoscopy was reported as normal in 15 patients and achalasia was suggested in only 21 of 33 barium examinations. Fourteen had been treated for gastrooesophageal reflux but none had been misdiagnosed as having cardiac or psychiatric disease. The annual incidence of achalasia in the Lothian region is 0.8/100,000 of population. Persistent dysphagia is the cardinal symptom of achalasia which presents throughout adult life. Nevertheless, recent onset achalasia is often misdiagnosed as gastrooesophageal reflux disease. Because endoscopy is frequently normal and the diagnosis is often not made by radiology, manometric investigation is necessary if the condition is to be recognised and treated at an early stage.

Adolescent

Systematic comparison of conventional oesophageal manometry with oesophageal motility while eating bread.

Conventional oesophageal manometry is seldom accompanied by symptoms and may indeed be normal in patients with a history of dysphagia. We have recently shown that oesophageal manometry during eating may be helpful in the evaluation of patients with dysphagia but there has been little systematic comparison of fed oesophageal motor patterns with conventional clinical manometry. Oesophageal manometry in response to water swallows and during eating was therefore examined in 58 consecutive patients who had been referred for clinical oesophageal function studies. The patients were divided into three groups according to the percentage of peristaltic activity during conventional manometry: group 1 (n = 21) had 100% peristalsis; group 2 (n = 29) had 1-99% peristalsis and group 3 (n = 8) were aperistaltic. All the patients in group 3 had achalasia and remained aperistaltic during eating, however, was less than with water swallows in both group 1 (53% compared with 100%) and group 2 (49% compared with 82.3%) patients. Synchronous contractions and non-conducted swallows were correspondingly increased during eating. Although there was a significant correlation between the amplitude of peristaltic contractions with water and bread in groups 1 and 2, mean peristaltic amplitudes were less with bread than with water swallows. The data show that there are substantial differences in the distal oesophageal motility patterns produced by water swallows and by eating. Conventional manometry with water swallows does not allow prediction of the fed oesophageal motility pattern, except in patients with achalasia.

Bread

Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease.

The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.

Adult

Definitions of dyspepsia.

The definition of the term dyspepsia and of derived terms such as organic dyspepsia, functional dyspepsia, reflux-like dyspepsia, and non-ulcer dyspepsia continues to provoke controversy. In recent literature, however, it is apparent that a measure of agreement is now emerging with regard to 'dyspepsia', which is considered simply to denote episodic or persistent symptoms that include abdominal pain or discomfort and which are referable to the upper gastrointestinal tract. Particular symptom patterns may justify the use of descriptions such as reflux-like dyspepsia, ulcer-like dyspepsia, or dysmotility-like dyspepsia, but these terms should not carry any implication that the symptom patterns can be attributed to particular pathogenetic processes. In many patients with dyspepsia, clinical assessment and investigation fail to identify any abnormality to which the symptoms can reasonably be attributed. The label of 'functional dyspepsia' is well-established medical parlance in these circumstances and is generally accepted as the converse of 'organic dyspepsia', which denotes dyspepsia for which a responsible disease process has been identified.

Dyspepsia

Esophageal pH monitoring.

In the 25 years since it was first described, prolonged esophageal pH monitoring has gained increasing acceptance and popularity as a diagnostic and research technique in GER disease. Some recent developments that have contributed to its attraction include compact portable recorders, computerized analysis, short monitoring periods, the good discriminant value of the simple measurement of percent monitoring time that pH is less than 4, and the symptom index, allowing correlation of symptoms with reflux events. Nevertheless, there remain areas of uncertainty with regard to reproducibility and the conditions of monitoring, in particular whether strict dietary control and controlled activity and posture are necessary. There is no universally accepted normal range of values, but it is now apparent that normal and abnormal GER are not appropriately differentiated by simply defining the upper limit of normal using a formula of the mean plus two standard deviations, so other statistical techniques have emerged. Indications for the technique include atypical symptoms, particularly noncardiac chest pain, respiratory symptoms, and, in young children, apneic attacks and recurrent vomiting associated with failure to thrive. The technique is having an impact on the assessment prior to, during, and after medical and surgical therapy for GER, as well as in helping to unravel the complexities of the pathogenesis of esophagitis.

Esophagitis, Peptic

Effect of gel fibre on gastric emptying and absorption of glucose and paracetamol.

To determine the part played by altered gastric emptying in the modification of glucose absorption by gel fibres, glucose tolerance tests were done in seven healthy volunteers with and without the addition of pectin to the ingested glucose solution and after pharmacological inhibition of gastric emptying with propantheline. Compared with the controls, pectin significantly reduced blood-glucose. Propantheline had a similar but more pronounced effect. Pectin and guar gum did not substantially alter glucose tolerance in a patient who had had total gastrectomy. In a further investigation, gastric emptying and paracetamol absorption were studied simultaneously in fourteen subjects. In eight of these the study was repeated after addition of guar gum and pectin to the ingested paracetamol. Both gastric emptying and paracetamol absorption were slower after gel fibre but the total absorption of the drug, reflected in urinary recovery, was not significantly reduced. The results suggest that the effects of guar gum and pectin on glucose tolerance and paracetamol absorption could be due simply to alteration in the rate of gastric emptying.

Absorption

Effects of 'elemental' diets on absorptive and enzymic activities and on 5-fluorouracil toxicity in rat small intestine.

1. Water absorption and cytoplasmic dipeptidase activities were determined in isolated rat small intestine after animals had fed on various 'elemental' diets or a standard rat diet and after a single injection of 5-fluorouracil. 2. Vivonex diets were associated with a decrease in dry weight of the small intestine and an increase in glucose and water absorption in vitro. 3. The nature of the dietary nitrogen profoundly affects the activities of intestinal peptidases. 4. Water absorption was severly depressed 3 days after 5-fluorouracil administration: the extent of depression was independent of the diet. Thus, any ameliorative effects of 'elemental' diets on 5-fluorouracil toxicity are unlikely to be mediated by direct protection of intestinal absorption.

Animals

Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying.

Gastric acid secretion, gastric emptying, fasting serum gastrin and the serum gastrin response to a meal were measured in duodenal ulcer patients before, and at least five days after completing prolonged treatment with cimetidine (1 or 2 g/day for four or eight weeks followed by 600 mg twice daily for six months). Fasting serum gastrin and the gastrin response were also measured during treatment. Compared with pretreatment values, fasting serum gastrin concentrations were raised both during and five to 31 days after stopping treatment (P less than or equal to 0.02). The integrated gastrin response and the rate of gastric emptying of the solid component of the meal were increased during treatment (P less than 0.001 and P less than 0.002 respectively) but returned to pretreatment levels after stopping therapy. No significant changes were observed in the basal or maximal acid outputs or the rate of emptying of the liquid component of the meal. The results imply that the hypergastrinaemia associated with long-term cimetidine therapy does not result in increased gastric acid secretion.

Cimetidine

High flow oxygen therapy for pneumatosis coli.

Symptomatic and radiological resolution of pneumatosis coli was achieved by intermittent high flow oxygen therapy in five patients. In each case the extent of the disease was defined by colonoscopy and contrast radiography before treatment. Despite the confirmation of pneumocyst resolution, recurrence of colonic gas cysts was noted in two patients at six months and one year after treatment. Bacteriological studies indicated that resolution of the disease, induced by oxygen therapy, was not associated with eradication of anerobic bacteria from stool and colonic mucosa. The clinical features and response to treatment of this group of patients are discussed, with particular reference to previously reported methods of oxygen administration.

Aged

A single scan technique for estimating acid output.

A single scan technique using 99mTc has been developed for the measurement of gastric acid output. After an overnight fast, pentagastrin (6 microgram/kg S.C.) was given 15 min before 99mTc (1 mCi i.v.), and a scan of the abdomen was performed 15 min later using a double-headed scanner. Accumulation of isotope within the stomach was then calculated from the scan and expressed as a percentage of the injected dose. Pentagastrin-stimulated intragastric activity correlated with acid output measured conventionally on a separate occasion (r = 0.87, P less than 0.0001). The test is rapidly performed with minimal inconvenience and discomfort to the patient, and the dose of irradiation used is small. The advantages of the method compared with intubation and gastric aspiration are discussed.

Gastric Acidity Determination

Kinetics of acetaminophen absorption and gastric emptying in man.

Eight healthy male volunteers ingested an aqueous solution containing acetaminophen (20 mg/kg) and a nonabsorbable isotopic marker. The concentrations of unconjugated acetaminophen in samples of blood plasma taken at frequent intervals were measured by gas-liquid chromatography. The data points followed a smooth curve in most cases and were fitted to the classical two-compartment pharmacokinetic model to obtain KA, the apparent first-order rate constant for absorption from the gastrointestinal tract. Gastric emptying was measured simultaneously from serial scintiscans of the subject's abdomen. The subjects were also studied after intramuscular injection of meperidine (150 mg) and pentazocine (60 mg) with and without naloxone (1.2 mg). The acetaminophen absorption curves and gastric emptying patterns were consistent with negligible absorption from the stomach. A new model is proposed in which the conventional single compartment used to represent the gastrointestinal tract is replaced by two compartments: one represents the stomach and the other the small intestine, from which absorption occurs rapidly. Pharmacokinetic analysis using this model showed good agreement in all cases, and provided an estimate of KA, the first-order rate constant for drug transfer from the intestinal lumen into the systemic circulation. The mean half-time for transfer was 6.8 +/- 0.9 min. As expected, KA was greater than KG (the first-order rate constant for gastric emptying), showing that gastric emptying was rate-limiting in the absorption of acetaminophen. The value of KA was greater than KA and the two were not related. The value of KA was not equal to KG in most studies because gastric emptying was not a single exponential process.

Acetaminophen

Changes in absorptive and peptide hydrolase activities in rat small intestine after administration of 5-fluorouracil.

1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil. 2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine. 3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal L-Leu-Gly hydrolase activity. 4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.

Animals

Premedication for upper gastrointestinal endoscopy: a comparative study of flunitrazepam, diazepam and neuroleptanalgesia.

Flunitrazepam or diazepam with atropine and a combination of phenoperidine, droperidol and cyclizine (neuroleptanalgesia) were compared as premedication in three groups of 25 patients undergoing routine upper gastrointestinal endoscopy. Drug doses were titrated carefully against response and all three regimes were found to be similar in terms of safety, patient co-operation, relaxation and speed of recovery. Neuroleptanalgesia however produced a statistically significant rise in endtidal pCO2 and systolic blood pressure. The benzodiazepines, and in particular flunitrazepam, produced a significantly greater amnesia for the procedure, patients given these drugs being more willing to undergo repeat endoscopy.

Anti-Anxiety Agents

Lower oesophageal sphincter response to gastrin--pharmacological or physiological?

The response of the lower oesophageal sphincter (LOS) to intragastric instillation of protein was assessed in 10 healthy volunteers. Sphincter pressures were measured by a rapid pull-through technique and serum gastrin concentrations during each test were determined by radioimmunoassay. Despite stimulation of gastrin release by protein instillation, no significant change in LOS pressure was observed. However, intravenous pentagastrin (0.25 and 0.5 microgram/kg) produced an immediate increase in sphincter pressure, which then returned to the basal level within four minutes. Thus, although pentagastrin is an effective pharmacological stimulant of the sphincter, endogenous gastrin appears not to be a physiological determinant of LOS pressure in man.

Adult