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Biomedical subjects

R H Holloway

Publications and source records attributed to R H Holloway.

At least 19 recordsLinked to original sources
PubMed2005

Assessment of oesophageal motor function using combined perfusion manometry and multi-channel intra-luminal impedance measurement in normal subjects.

Multichannel intraluminal impedance (MII) is being used increasingly to assess oesophageal bolus clearance. However, there is no good standardization of the impedance parameters that define 'effective bolus clearance'. The aim of this study was to define these important impedance parameters and to determine their normal values. Concurrent perfusion manometry and MII were performed in 42 healthy volunteers. Ten, 5-mL liquid (saline) boluses and then, 10x5-mL low impedance viscous boluses were tested in each subject in the right-lateral position. Normal values for bolus presence time (BPT) at each site and total bolus transit time (TBTT) were determined from either 'normal' peristaltic responses (amplitude>or=30 mmHg in distal oesophagus) or 'super-normal' peristaltic responses (amplitudes>or=50 mmHg at all sites). The relationship between BPT and TBTT within a response and per-individual performance was determined. A total of 840 swallows of liquids and viscous responses were analysed. BPT and TBTT of viscous swallows were longer than those for liquids. Non-peristaltic responses were significantly more likely not to clear a viscous than a liquid bolus. Within a response, the number of sites with prolonged BPT strongly predicted the incidence of prolonged TBTT. Using impedance criteria, normal oesophageal bolus clearance is defined when an individual completely clears at least 70% of liquid responses and at least 60% of viscous responses. This study provides normal values for impedance measurement of bolus clearance when combined with perfusion manometry. These values will allow standardization of impedance application in oesophageal function testing, in both research and clinical setting.

Adolescent↗
PubMed2005

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease.

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 +/- 23 s and 41 +/- 5 s, respectively, P < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.

Adult↗
PubMed2003

Delivery of radiofrequency energy to the lower oesophageal sphincter and gastric cardia inhibits transient lower oesophageal sphincter relaxations and gastro-oesophageal reflux in patients with reflux disease.

BACKGROUND AND AIMS: Radiofrequency energy (RFe) treatment to the lower oesophageal sphincter (LOS) and gastric cardia is a new luminally delivered therapy proposed as an alternative treatment for gastro-oesophageal reflux disease (GORD). However, it is unclear how RFe achieves its antireflux effect. This study investigated the effects of RFe on mechanisms of spontaneous reflux in patients with GORD. METHODS: Twenty patients with GORD underwent endoscopy, symptom evaluation, and combined postprandial oesophageal manometry and pH monitoring before and six months after RFe, and 24 hour ambulatory pH monitoring before and at six and 12 months after treatment. RESULTS: RFe reduced the rate of postprandial transient LOS relaxations from 6.8 (5.7-8.1) (median (interquartile range) per hour to 5.2 (4.2-5.8) per hour (p<0.01), and increased mean basal LOS pressure from 5.2 (SEM 0.3) mm Hg to 8.0 (SEM 0.4) mm Hg (p<0.01). The number of reflux events was reduced from 10 (2-15.3)/3 hours to 5 (3.5-8.5)/3 hours (p<0.05) and there was an associated significant reduction in acid exposure time from 5.4% (0.4-14.7) to 3.9% (0.4-6.6) (p<0.05). RFe significantly reduced ambulatory oesophageal acid exposure from 10.6% (7.8-13.0) to 6.8% (3.1-9.1) (p<0.01) at six months and 6.3% (4.7-10.9) (p<0.05) at 12 months. All patients required acid suppressant medication for symptom control before RFe. Six months after treatment, 15 patients (75%) were in symptomatic remission and 13 (65%) at 12 months. CONCLUSIONS: RFe has significant effects on LOS function that are associated with improvement in the antireflux barrier. Uncontrolled clinical data also suggest a beneficial effect in the control of reflux symptoms in these patients.

Adult↗
PubMed2002

Role of CCK(A) receptors in postprandial lower esophageal sphincter function in morbidly obese subjects.

To reduce weight, some morbidly obese patients are treated with an intragastric balloon, often resulting in increased reflux symptoms. As transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism underlying reflux and can be reduced by cholecystokinin-A (CCK(A)) blockade, we hypothesized that the CCK(A)-receptor antagonist loxiglumide could reduce gastroesophageal reflux in these subjects. Postprandial manometric studies were performed in 12 obese subjects during infusion of placebo or loxiglumide. Before balloon placement, loxiglumide did not significantly reduce the rate of TLESRs but attenuated the postprandial decrease in LES pressure. After 10 weeks of balloon treatment, loxiglumide significantly reduced the rate of TLESRs. Postprandial LES pressure was significantly increased, whereas the meal-induced decrease in LES pressure was absent. Neither loxiglumide nor balloon placement affected gastroesophageal reflux. In conclusion, CCK(A) receptors play an important role in post-prandial LES pressure decrease and are involved in the reflex pathway underlying the triggering of TLESRs, at least after balloon placement.

Adult↗
PubMed2002

Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease. METHODS: In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7-15.5)). CONCLUSIONS: In patients with reflux disease, the GABA(B) agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux disease.

Adult↗
PubMed2001

Systemic pharmacomodulation of transient lower esophageal sphincter relaxations.

Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism of reflux in patients with gastroesophageal reflux disease. They are therefore attractive targets for pharmacotherapy. During the past 5 years, there has been a burgeoning interest in the neural pathways that control these events and in the pharmacologic receptors involved in these pathways. Several agents have been shown to reduce the rate of TLESRs, including cholecystokinin-A antagonists, anticholinergic agents, nitric oxide synthase inhibitors, morphine, somatostatin, serotonin type 3-receptor antagonists, and gamma-aminobutyric acid-B (GABA(B)) agonists. Their predominant site of action appears to be on either the afferent pathways and/or the central integrative mechanisms within the dorsal vagal complex in the brainstem. Most of the agents tested are unsuitable for clinical use either because of side effects or because of the lack of an orally effective formulation. The most promising agents identified to date are the GABA(B) agonists. Baclofen, the prototype GABA(B) agonist, inhibits the rate of TLESRs by more than 50%. Control of TLESRs is a major new approach to the treatment of reflux disease. It is likely to be applicable to the majority of patients, particularly those without macroscopic mucosal lesions or only mild erosive disease. Further development of more effective agents will depend both on a better understanding of the neural pathways and receptors involved in the control of TLESRs, as well as on investigation of other novel agents. At present, inhibition of TLESRs is at the threshold of transition from concept to practical use. Whether it makes the final leap into the mainstream of therapy will depend on the development of new, novel, and well-targeted pharmacologic agents.

Cholecystokinin↗
PubMed2000

Esophageal body motor response to reflux events: secondary peristalsis.

The esophageal body is a major component of the antireflux mechanism. Disruption of esophageal peristalsis affects both volume clearance and delivery of swallowed saliva to the distal esophageal body. The esophageal body responds to reflux by an increase in primary peristalsis through stimulation of swallowing and secondary peristalsis through esophageal distension. Primary peristalsis is the most common motor event after reflux and accounts for up to 90% of initial and subsequent motor activity. Secondary peristalsis is uncommon but may be important during sleep when swallowing is relatively suppressed. Some patients with reflux disease, particularly those with severe esophagitis, exhibit impaired esophageal responses to reflux. It is likely that this impairment prolongs acid clearance and may also influence the proximal extent of the refluxate within the esophageal body.

Deglutition↗
PubMed2000

Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects.

BACKGROUND & AIMS: Transient lower esophageal sphincter (LES) relaxations are the major mechanism of gastroesophageal reflux in normal subjects and in most patients with reflux disease. gamma-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter within the central nervous system which is present in regions of the brainstem that are believed to mediate transient LES relaxations. The aim of this study was to investigate the effect of a GABA(B) agonist baclofen on postprandial gastroesophageal reflux and transient LES relaxations. METHODS: In 20 healthy volunteers, esophageal motility and pH were measured, with the subjects in the sitting position, for 3 hours after a 3000-kJ mixed nutrient meal. On separate days at least 1 week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal. RESULTS: Baclofen significantly reduced the rate of reflux episodes by more than 60% from 1.0 (0.3-2.7) to 0.3 (0-1.0) per hour (median [interquartile range]). Baclofen also reduced the rate of transient LES relaxations from 5.7 (4.9-7.8) to 2.2 (1.3-3.8) per hour and increased basal LES pressure from 8.7 +/- 1.4 to 10.8 +/- 0.8 mm Hg. CONCLUSIONS: In normal human subjects, the GABA(B) agonist baclofen significantly inhibits gastroesophageal reflux by inhibition of transient LES relaxations. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux in patients with gastroesophageal reflux disease.

Adolescent↗
PubMed2000

Belching and bloating: facts and fantasy after antireflux surgery.

BACKGROUND: Fundoplication is commonly complicated by belching difficulty and abdominal bloating. Postoperative belching ability, however, is difficult to assess; subjective patient reporting is often used but may be unreliable. Manometric measurement of the gastro-oesophageal 'common cavity' is an objective marker of gastro-oesophageal gas reflux. METHODS: Twenty patients who had undergone Nissen fundoplication and 11 healthy controls underwent oesophageal manometry at rest and during gastric distension for 10 min with 750 ml of gas. RESULTS: Half of the patients reported an inability to belch; the other half reported varying degrees of belching difficulty, most of whom were rarely able to relieve bloating by belching. During gastric distension, none of the patients had transient lower oesophageal sphincter relaxation, while the controls had a median of 1 (range 0-1). Patients had fewer common cavities than controls; however, none of the belch urges experienced during gastric distension in patients was associated with a common cavity, compared with 48 per cent in controls. CONCLUSION: After fundoplication, patients do not belch as a result of gastro-oesophageal gas reflux; rather it may be due to oesophagopharyngeal reflux of swallowed air. Subjective reporting of belching ability is inaccurate and manometric measurement of common cavities provides a better means of assessment.

Adult↗
PubMed2000

Evaluation of miniature manometric techniques for the measurement of esophageal body pressure waves.

BACKGROUND AND AIMS: Perfused miniature manometric assemblies with lumina of 0.4-0.5 mm i.d. have been developed. Reduced luminal size offers the advantages of reduced assembly bulk and increased assembly complexity with greater numbers of lumina and lower manometric infusion volumes because of a slower perfusion rate. This study investigated the recording fidelity of miniature manometric assemblies in the measurement of esophageal peristalsis. METHODS: Four miniature manometric assemblies, each containing manometric lumina of either 0.4 or 0.5 mm i.d., were evaluated at 100 and 180 cm lengths. The fidelity of miniature manometric luminal recordings were evaluated in vivo during esophageal peristalsis by using a simultaneous comparison with the standard lumina and an intraluminal strain gauge. RESULTS: During esophageal peristalsis, miniature manometric lumina recorded the peak amplitude of pressure waves, with an accuracy at perfusion rates of 0.04 mL/min (0.4 mm, i.d.) and 0.15 mL/min (0.5 mm, i.d.). CONCLUSION: Miniature manometric assemblies of lengths that are practical for use in humans are suitable for recording esophageal peristalsis.

Adult↗
PubMed2000

The anti-reflux barrier and mechanisms of gastro-oesophageal reflux.

The lower oesophageal sphincter (LOS) is the major component of the anti-reflux barrier. The majority of reflux episodes occur because of intermittent brief complete lower oesophageal sphincter relaxations, transient LOS relaxations, rather than from chronic absence of LOS pressure. Recent advances in the understanding of the neural mechanisms and the receptors involved in the triggering of transient LOS relaxations have provided new insights into their control and offer the potential for the development of pharmacological therapy of reflux based on control of these events. Extrinsic support by the crural diaphragm is also important and loss of this support through development of hiatus hernia significantly compromises LOS function. This chapter reviews the components of the anti-reflux barrier, the patterns and mechanisms of LOS dysfunction underlying reflux episodes, and the interplay between sphincteric and non-sphincteric factors.

Esophagitis↗
PubMed2000

Endoscopy-negative reflux disease.

The majority of patients with symptoms of gastro-oesophageal reflux have no endoscopic evidence of oesophagitis. There has been remarkably little systematic gathering of information about this group of patients. It is commonly believed that they have a mild form of reflux disease, with low levels of dysfunction that usually respond to simple therapeutic measures. Emerging data from recent studies indicate that this is not the case. Endoscopy-negative patients have symptom severities comparable to those with erosive disease, and which significantly impair their quality of life. The limited data available on the pathophysiology of endoscopy-negative reflux disease suggest that, in the majority of patients, it is as much a disease of excessive gastro-oesophageal reflux as it is in patients with oesophageal lesions. The same principles that apply to successful treatment in patients with oesophagitis also hold true for patients with endoscopy-negative disease.

Anti-Ulcer Agents↗
PubMed2000

Effect of atropine on proximal gastric motor and sensory function in normal subjects.

BACKGROUND AND AIMS: Distension of the proximal stomach is a major stimulus for triggering transient lower oesophageal sphincter (LOS) relaxations. We have shown recently that atropine inhibits triggering of transient LOS relaxations in both normal subjects and patients with gastro-oesophageal reflux disease. Atropine could potentially act centrally by inhibiting the central integrating mechanism in the brain stem, or act peripherally by altering the response of the stomach to distension. The aim of this study was to investigate the effect of atropine on fasting gastric compliance and postprandial gastric tone using an electronic barostat. METHODS: Fasting and postprandial proximal gastric motor and sensory functions were assessed in 10 normal healthy volunteers. Oesophageal manometry and pH were simultaneously measured. On separate days, atropine (15 microg/kg bolus, 4 microg/kg/h intravenous infusion) or saline was given and maintained for the duration of the recording period. RESULTS: In the fasting period, atropine significantly reduced minimum distending pressure (5.5 (0.4) v 4.4 (0.4) mm Hg; p<0.005) and increased proximal gastric compliance (81.3 (5.3) v 102. 1 (8.7) ml/ mm Hg; p<0.05). In response to a meal, maximal gastric relaxation was similar on both study days. However, during atropine infusion, there was no recovery of proximal gastric tone in the two hour postprandial observation period. Postprandial fullness scores were higher during atropine infusion and correlated with changes in intrabag volume. Atropine significantly reduced the rate of postprandial transient LOS relaxations: first hour, 7.0 (5.3-10.0) v 3.0 (1.0-4.0) (p<0.02); second hour, 5.0 (3.3-5.8) per hour v 1.0 (0-3.0) per hour (p<0.05). CONCLUSIONS: In humans, fasting and postprandial proximal gastric motor function is under cholinergic control. Atropine induced inhibition of transient LOS relaxations is unlikely to be caused by its effect on the proximal stomach, but rather by a central action on the integrating mechanisms in the brain stem.

Adult↗