Vagal function in relation to gastro-oesophageal reflux and associated motility changes.

Vagal function in 28 patients with gastro-oesophageal reflux was examined by determining gastric secretory response to insulin-induced hypoglycaemia and pulse-rate variation with respiration. Gastric secretory studies were also performed on 13 patients with duodenal ulcer who had not undergone operations. In all patients the presence and degree of oesophagitis were determined endoscopically and mucosal biopsy and oesophageal manometry were performed. Seven of the 28 patients with gastro-oesophageal reflux showed evidence of impaired vagal efferent function in the upper alimentary tract. No such impairment was found in those patients who showed manometric evidence of oesophageal spasm secondary to gastro-oesophageal reflux. Low pulse-rate variation with respiration was found in 12 of 27 patients with gastro-oesophageal reflux, suggesting dysfunction of cardiac vagal fibres. Impairment of efferent vagal supply may be a causative factor in some patients with gastr-oesophageal reflux but does not seem to be important in oesophageal spasm secondary to gastro-oesophageal reflux.     

Comparison of barium swallow and ultrasound in diagnosis of gastro-oesophageal reflux in children.

Fifty one infants and older children with suspected gastro-oesophageal reflux entered a study comparing the diagnostic accuracy of a standard barium swallow examination with that of ultrasound scanning. All children were examined by both techniques. In 40 cases there was unequivocal agreement between the examinations. Of the remaining patients, four had definite reflux by ultrasonic criteria but showed no evidence of reflux on barium swallow examination, four had positive findings on ultrasound but showed only minimal reflux on barium swallow, and one showed minimal reflux on ultrasound but had a negative barium meal result. In two children the ultrasound study was inconclusive. Ultrasound has an important role in the diagnosis and follow up of patients under the age of 5 years with gastro-oesophageal reflux.     

Effect of imidapril in dipper and nondipper hypertensive patients: comparison between morning and evening administration

The purpose of the study was to identify differences in the patterns of efficacy and duration of effects of imidapril administered at different times of the day (morning versus evening) in dipper and nondipper hypertensive patients. Twenty patients with untreated hypertension were classified into two groups: dippers (n = 9) and nondippers (n = 11). Imidapril (10 mg) was given at 07:00 or 18:00 for 4 weeks in a crossover fashion. Blood pressure (BP) and heart rate (HR) were monitored before and after morning and evening treatment every 30 min for 48h by ambulatory BP monitoring (ABPM). In dipper hypertension, the mean 48h BP was reduced with both doses. The decrease in the diurnal BP was stronger when the drug was administered in the evening than morning, but without significant difference. In nondipper hypertension, the systolic BP decreased at night with both doses, but the extent of the nocturnal reduction in systolic BP was greater after morning therapy. There were no significant differences in the decrease in BP during the day or night between the morning and evening administrations. When imidapril was administered in the morning, its serum concentration reached a maximum at 16:00, and when the drug was administered in the evening, it reached a maximum at 6:00. In dipper hypertension, the time taken for the blood concentration of imidapril to reach a maximum changed depending on its time of administration, and the time when the maximum antihypertensive effect of the drug appeared was different. In nondipper hypertension, decreases in the BP were confirmed at night regardless of the time of administration; this might be caused by angiotensin converting enzyme (ACE) inhibitors effectively blocking the BP from increasing by activating the parasympathetic nervous system. Therefore, when assessing the effectiveness of antihypertensive agents, factors such as the various patterns of BP before therapy and administration time must be considered.     

Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux

Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Studies in humans or in animals have suggested that these responses involve cholinergic nerves. The purpose of this study was to investigate the role of the efferent vagal component on airway microvascular leakage induced by instillation of hydrochloric acid (HCl) into the oesophagus of guinea-pigs and the subtype of muscarinic receptors involved. Airway microvascular leakage induced by intra-oesophageal HCl instillation was abolished by bilateral vagotomy or by the nicotinic receptor antagonist, hexamethonium. HCl-induced leakage was inhibited by pretreatment with atropine, a non-specific muscarinic receptor antagonist, and also by pretreatment with either pirenzepine, a muscarinic M(1) receptor antagonist, or 4-DAMP, a muscarinic M(3) receptor antagonist. Pirenzepine was more potent than atropine and 4-DAMP. These antagonists were also studied on airway microvascular leakage or bronchoconstriction induced by intravenous administration of acetylcholine (ACh). Atropine, pirenzepine and 4-DAMP inhibited ACh-induced airway microvascular leakage with similar potencies. In sharp contrast, 4-DAMP and atropine were more potent inhibitors of ACh-induced bronchoconstriction than pirenzepine. Methoctramine, a muscarinic M(2) receptor antagonist, was ineffective in all experimental conditions. These results suggest that airway microvascular leakage caused by HCl intra-oesophageal instillation involves ACh release from vagus nerve terminals and that M(1) and M(3) receptors play a major role in cholinergic-mediated microvascular leakage, whereas M(3) receptors are mainly involved in ACh-induced bronchoconstriction.     

Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms.

During 24 hour oesophageal pH monitoring 52 patients who had angina pectoris and normal coronary angiograms underwent exercise testing, as far as their symptoms allowed, on a treadmill to determine whether gastro-oesophageal reflux occurred during exertion. In 11 patients the 24 hour oesophageal pH score was abnormally high; 10 of these showed exertional gastro-oesophageal reflux, and in nine this was associated with their usual chest pain. A further 13 patients had a normal 24 hour pH score but had exertional reflux coincident with chest pain during exercise testing. The mean lower oesophageal sphincter pressure in both of these groups of patients was appreciably lower than that in 28 patients who had a normal 24 hour pH score and no exertional reflux. These findings suggest that exertional gastro-oesophageal reflux accounts for the symptoms of a large proportion of patients who have angina pectoris and normal coronary angiograms and that oesophageal pH monitoring during exercise testing on a treadmill enables this group of patients to be identified.     

Ambulatory electrocardiography (Holter monitoring) in caged monkeys

A swivel-tethering and jacket system was used in conjunction with vinyl patch electrodes and Holter recorders to obtain continuous ECG recordings in 12 rhesus monkeys on a long-term (12 day) study. Animals were custom-fitted with nylon mesh jackets that were connected to a swivel unit by a flexible, stainless steel tether. Lead wires from the chest electrodes passed through the tether to the electrical swivel apparatus located at the top of the cage. Wires from the upper part of the swivel were attached to a reel-to-reel Holter recorder. This technique was used to obtain 24-h continuous ECG recordings, which were later processed using a computer-assisted Holter analysis system.     

Single-mouse urine collection and pH monitoring system.

A glass cage with minimal surface area was designed and used to house mice for 24-hour urine collections. An experiment was performed with a radio-labeled compound excreted in the urine to assess the collection efficiency of the cage. In this experiment 74.2 +/- 6.5% of the excreted radioactivity was recovered in the urine, with 25.8 +/- 6.5% found adhering to the cage surfaces. When a flow-through pH electrode, meter, and recorder were attached, the system provided a continuous pH versus time urination record.