Biomedical subjects

Richard H Holloway

Publications and source records attributed to Richard H Holloway.

18 recordsLinked to original sources

PubMed2007

Proximal gastric motility in critically ill patients with type 2 diabetes mellitus.

AIM: To investigate the proximal gastric motor response to duodenal nutrients in critically ill patients with long-standing type 2 diabetes mellitus. METHODS: Proximal gastric motility was assessed (using a barostat) in 10 critically ill patients with type 2 diabetes mellitus (59 +/- 3 years) during two 60-min duodenal infusions of Ensure (1 and 2 kcal/min), in random order, separated by 2 h fasting. Data were compared with 15 non-diabetic critically ill patients (48 +/- 5 years) and 10 healthy volunteers (28 +/- 3 years). RESULTS: Baseline proximal gastric volumes were similar between the three groups. In diabetic patients, proximal gastric relaxation during 1 kcal/min nutrient infusion was similar to non-diabetic patients and healthy controls. In contrast, relaxation during 2 kcal/min infusion was initially reduced in diabetic patients (P < 0.05) but increased to a level similar to healthy humans, unlike non-diabetic patients where relaxation was impaired throughout the infusion. Duodenal nutrient stimulation reduced the fundic wave frequency in a dose-dependent fashion in both the critically ill diabetic patients and healthy subjects, but not in critically ill patients without diabetes. Fundic wave frequency in diabetic patients and healthy subjects was greater than in non-diabetic patients. CONCLUSION: In patients with diabetes mellitus, proximal gastric motility is less disturbed than non-diabetic patients during critical illness, suggesting that these patients may not be at greater risk of delayed gastric emptying.

Adult↗

PubMed2007

Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release.

Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3-O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min (P<0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine (P<0.005). Overall, blood glucose (P<0.01) and plasma 3-OMG concentrations (P<0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially (t=20 min) lower during hyoscine (P<0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.

3-O-Methylglucose↗

PubMed2007

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.

OBJECTIVE: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. MEASUREMENTS AND MAIN RESULTS: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. CONCLUSIONS: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.

APACHE↗

PubMed2007

Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness.

OBJECTIVE: This study aimed to a) compare the efficacy of metoclopramide and erythromycin in the treatment of feed intolerance in critical illness; and b) determine the effectiveness of "rescue" combination therapy in patients who fail monotherapy. DESIGN: Randomized controlled trial. SETTING: Level III mixed medical and surgical intensive care unit. PATIENTS: Ninety mechanically ventilated, medical patients with feed-intolerance (gastric residual volume>or=250 mL). INTERVENTIONS: Patients received either metoclopramide 10 mg intravenously four times daily (n=45) or erythromycin 200 mg intravenously twice a day (n=45) in a double-blind, randomized fashion. After the first dose, nasogastric feeding was commenced and 6-hourly nasogastric aspirates were performed. If a gastric residual volume>or=250 mL recurred on treatment, open-label, combination therapy was given. Patients were studied for 7 days. Successful feeding was defined as 6-hourly gastric residual volume<250 mL with a feeding rate>or=40 mL/hr. MEASUREMENTS AND MAIN RESULTS: Demographic data, blood glucose levels, and use of inotropes, opioids, and benzodiazepines were similar between the two groups. After 24 hrs of treatment, both monotherapies reduced the mean gastric residual volume (metoclopramide, 830+/-32 mL to 435+/-30 mL, p<.0001; erythromycin, 798+/-33 mL to 201+/-19 mL, p<.0001) and improved the proportion of patients with successful feeding (metoclopramide=62% and erythromycin=87%). Treatment with erythromycin was more effective than metoclopramide, but the effectiveness of both treatments declined rapidly over time. In patients who failed monotherapy, rescue combination therapy was highly effective (day 1=92%) and maintained its effectiveness for the study duration (day 6=67%). High pretreatment gastric residual volume was associated with poor response to prokinetic therapy. CONCLUSIONS: In critical illness, erythromycin is more effective than metoclopramide in treating feed intolerance, but the rapid decline in effectiveness renders both treatments suboptimal. Rescue combination therapy is highly effective, and further study is required to examine its role as the first-line therapy.

Critical Illness↗

PubMed2006

Relationship between pressure wave amplitude and esophageal bolus clearance assessed by combined manometry and multichannel intraluminal impedance measurement.

OBJECTIVES: Esophageal wave amplitude is an important determinant of esophageal clearance. A threshold of 30 mmHg is widely accepted as the threshold for effective clearance in the distal esophagus. However, the precise relationship between wave amplitude and clearance has received relatively little attention. The aim of this study was to assess the impact of peristaltic wave amplitude on esophageal volume clearance using multiple intraluminal impedance (MII) measurement. METHODS: Concurrent manometry and MII were performed on 42 healthy asymptomatic volunteers and 13 patients with ineffective esophageal motility. Esophageal motility was measured at four sites 5-cm apart, starting 2 cm above the lower esophageal sphincter. MII was measured at corresponding sites with electrodes incorporated into the manometric assembly. Ten 5-mL liquid (saline) boluses and ten 5-mL low impedance viscous boluses were tested in each subject. Pressure wave amplitude was determined at each site as well as peristaltic success of the responses. Bolus clearance was measured from individual recording segment and from the esophagus as a whole. RESULTS: The proportion of liquid boluses cleared at each site was directly related to wave amplitude and did not increase significantly above a threshold of 25 mmHg in the proximal esophagus, 22 mmHg in the mid-esophagus, and 30 mmHg in the distal esophagus. Corresponding wave amplitudes for total esophageal clearance were 35-40 mmHg. There was a good correlation between the wave amplitude at one site of the esophagus and those of the rest of the esophagus. For both liquid and viscous boluses, the likelihood of impaired clearance was directly related to the number of segments with hypotensive pressure waves. CONCLUSION: The findings confirm the validity of the wave amplitude threshold required for effective liquid bolus clearance and have established the amplitude threshold for clearance of viscous boluses. However, the number of hypotensive pressure waves required for the definition of ineffective motility may be too low.

Adolescent↗

PubMed2006

Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial.

PURPOSE: The aim of this study was to compare the toxicity and efficacy of radiation therapy (RT) for localized carcinoma of the prostate, using a hypofractionated (55 Gy/20 fractions/4 weeks) vs. a conventionally fractionated (64 Gy/32 fractions/6.5 weeks) dose schedule. METHODS AND MATERIALS: A total of 217 patients were randomized to either the hypofractionated (108 patients) or the conventional (109 patients) dose schedule, with planning with two-dimensional (2D) CT scan planning methodology in the majority of cases. All patients were followed for a median of 48 (6-108) months. Gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated before RT and after its completion using modified late effects of normal tissue-subjective, objective, management, analytic (LENT-SOMA) scales and the European Organization for Research and Treatment of Cancer sexual function questionnaire. Efficacy of RT based on clinical, radiologic, and prostate-specific antigen data were also evaluated at baseline and after RT. RESULTS: Gastrointestinal and GU toxicity persisted 5 years after RT and did not differ between the two dose schedules other than in regard to urgency of defecation. However, 1-month GI toxicity was not only worse in patients with the hypofractionated RT schedule but also adversely affected daily activities. Nadir prostate-specific antigen values occurred at a median of 18.0 (3.0-54.0) months after RT. A total of 76 biochemical relapses, with or without clinical relapses, have occurred since; of these, 37 were in the hypofractionated and 39 in the conventional schedule. The 5-year biochemical +/- clinical relapse-free and overall survival was 55.9% and 85.3% respectively for all patients, and did not differ between the two schedules. CONCLUSIONS: Radiation therapy for prostate carcinoma causes persistent GI toxicity that is largely independent of the two dose schedules. The hypofractionated schedule is equivalent in efficacy to the conventional schedule.

Adult↗

PubMed2006

Long-standing type II diabetes mellitus is not a risk factor for slow gastric emptying in critically ill patients.

OBJECTIVE: Delayed gastric emptying (GE) is common both in critical illness and in patients with diabetes mellitus (DM). The effect of DM on the incidence of slow GE in these patients is unknown. We evaluated the effect of DM on liquid GE in critically ill patients. METHODS: Retrospective analysis of GE using a standard [13C]octanoic acid breath test in 12 type 2 DM patients compared with (a) 44 critically ill patients without DM, including (b) a subgroup of 15 age- and sex-matched patients and (c) 15 healthy volunteers. We determined the gastric emptying coefficient (GEC) and the gastric half-emptying time (t50). Mean APACHE II scores, blood glucose levels and use of morphine were similar between patient groups. RESULTS: GE was faster in critically ill patients with DM (t50 122 +/- 11 min, GEC: 3.8 +/- 0.3) than in patients without DM (t50 168 +/- 16 min, GEC 2.8 +/- 0.1) and in age- and sex-matched controls (t50 165 +/- 13 min, GEC 2.7 +/- 0.2) and was similar to that in healthy volunteers (t50 148 +/- 13 min, GEC 3.5 +/- 0.1). The proportion of patients with slow emptying (GEC < 3.2) was greater in non-DM (all = 56%, matched = 60%) than in DM patients (25%) and healthy subjects (26%). CONCLUSION: Long-standing type diabetes mellitus is not a risk factor for slow GE in critically ill patients.

APACHE↗

PubMed2006

Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study.

INTRODUCTION: Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients. METHODS: Studies were performed in 19 unselected mechanically ventilated critically ill patients (12 males; 48 +/- 7 years old) in a randomised, single-blind fashion. Subjects received a 60-minute duodenal infusion of Ensure at either 1 or 2 kcal/minute. Blood samples were collected at baseline and at 20, 40, 60, and 180 minutes following commencement of the nutrient infusion for the measurement of plasma PYY and CCK concentrations (using radioimmunoassay). Patient data were compared to 24 healthy subjects (17 males; 43 +/- 2 years old). RESULTS: Fasting PYY concentration was higher in patients (P < 0.05), particularly in those with feed intolerance (P < 0.05). Plasma PYY concentrations were higher in patients during nutrient infusion (area under the curve [AUC] at 1 kcal/minute: 2,265 +/- 718 versus 1,125 +/- 138 pmol/l.min, P < 0.05; at 2 kcal/minute: 2,276 +/- 303 versus 1,378 +/- 210 pmol/l.min, P = 0.01) compared to healthy subjects. The magnitude of PYY elevation was greater in patients during the 1 kcal/minute infusion (AUC: 441 +/- 153 versus 186 +/- 58 pmol/l.min, P < 0.05), but not the 2 kcal/minute infusion. Fasting and nutrient-stimulated plasma CCK concentrations were higher in patients (P < 0.05). There was a relationship between plasma PYY and CCK concentrations during fasting (r = 0.52, P < 0.05) and nutrient infusion (r = 0.98, P < 0.0001). CONCLUSION: In critical illness, both fasting and nutrient-stimulated plasma PYY concentrations are elevated, particularly in patients with feed intolerance, in conjunction with increased CCK concentrations.

Adult↗

PubMed2005

Inhibition of transient lower esophageal sphincter relaxations by electrical acupoint stimulation.

Acupuncture has been shown to modulate visceral sensation and function. Traditionally, stimulation at the Neiguan (pericardial meridian) has been used to treat upper gastrointestinal symptoms. Some of the effects of acupuncture may be mediated through release of endogenous opioids and are reversed by naloxone. Gastric distension is the major trigger for transient lower esophageal sphincter (LES) relaxations (TLESRs). The aim of this study was to investigate the effect of electric stimulation at the Neiguan and naloxone on the TLESRs. In 14 healthy volunteers, electrical acupoint stimulation was applied at the Neiguan and a sham point on the hip in randomized order on the same day. In 12 healthy volunteers, the effects of naloxone (80 microg/kg iv bolus injection) and saline on electrical acupoint stimulation were compared on separate days at least 1 wk apart. Esophageal motility was measured during distension of the proximal stomach with 500 ml of air using a barostat balloon. Electric acupoint stimulation at the Neiguan decreased the rate of TLESRs by approximately 40% from a median of 6/h to 3.5/h (P < 0.02). Acupoint stimulation had no effect on basal LES pressure, the residual LES pressure during TLESRs, the duration of TLESRs, or gastrointestinal symptoms of fullness, bloating, discomfort, or nausea. The effect of acupoint stimulation was not inhibited by naloxone. Electric acupoint stimulation at the Neiguan significantly inhibits the frequency of TLESRs in response to gastric distention in healthy subjects. This effect does not appear to be mediated through mu-opioid receptors.

Acupuncture Points↗

PubMed2005

Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism of gastroesophageal reflux but are not the cause of reflux disease.

In healthy subjects, the rate of acid reflux during transient lower esophageal sphincter relaxations (TLESRs) is more frequent at the proximal margin of the LES. In this study, we investigated the hypothesis that the rate of acid reflux at the proximal margin of LES during TLESRs is similar in reflux disease to that in healthy subjects. Concurrent esophageal manometry and pH monitoring were performed in the sitting position for 3 hr after a standard meal in 10 patients with reflux disease and 10 age-matched healthy controls. The rate of TLESRs in patients with reflux disease (5.0/hr [3.3-6.7]; median [interquartile range]) was similar to that of controls (4.5/hr [3.7-5.7]). The incidence of acid reflux 7 cm above the LES during TLESRs in patients (48.1% [27.2-71.4%]) was significantly higher than that in controls (10.9% [0.0-18.8%]) but there was no difference 2 cm above the LES (75.0 [69.2-87.5] vs. 74.3 [55.5-90.0%]). The rate of TLESRs and the incidence of acid reflux during TLESRs are not increased in reflux disease. These findings, therefore, indicate that reflux disease is not a disorder of TLESRs and relates more to the proximal extent of the refluxate.

Adult↗

PubMed2005

Mechanisms of gastroesophageal reflux in critically ill mechanically ventilated patients.

BACKGROUND & AIMS: Gastroesophageal reflux is a major problem in mechanically ventilated patients and may lead to pulmonary aspiration and erosive esophagitis. Transient lower esophageal sphincter relaxations are the most common mechanism underlying reflux in nonventilated patients. The mechanisms that underlie reflux in critically ill ventilated patients have not been studied. The aim of this study was to determine the mechanisms underlying gastroesophageal reflux in mechanically ventilated patients in the intensive care unit. METHODS: In 15 mechanically ventilated intensive care unit patients, esophageal motility, pH, and intraluminal impedance (11/15 patients) were recorded for 1 hour before and 5 hours during continuous nasogastric feeding. RESULTS: Basal lower esophageal sphincter pressure was uniformly low (2.2 +/- 0.4 mmHg). The median (interquartile range) acid exposure (pH <4) was 39.4% (0%-100%) fasting and 32% (7.5%-94.2%) fed. Acid reflux occurred in 10 patients, but slow drifts in esophageal pH were also an important contributor to acid exposure. If esophageal pH decreased to pH <4, it tended to remain so for prolonged periods. A total of 46 acid reflux events were identified. Most (55%) occurred because of absent lower esophageal sphincter pressure alone; 45% occurred during straining or coughing. CONCLUSIONS: Gastroesophageal reflux in mechanically ventilated patients is predominantly due to very low or absent lower esophageal sphincter pressure, often with a superimposed cough or strain. These data suggest that measures that increase basal LES pressure may be useful to prevent reflux in ventilated patients.

Adult↗

PubMed2005

Multichannel intraluminal impedance monitoring in the evaluation of patients with non-obstructive Dysphagia.

BACKGROUND: Non-obstructive dysphagia (NOD) often poses diagnostic problems. The aim of this study was to evaluate the value of the addition of multichannel intraluminal impedance (MII) recording to esophageal manometry in the work-up of patients with NOD. METHODS: A total of 40 consecutive patients with NOD underwent combined esophageal MII recording and perfusion manometry. Ten liquid and 10 viscous boluses were tested in each patient. Values for bolus presence time (BPT) at each of the four recording sites and total bolus transit time (TBTT) were calculated. Bolus transit (BT) was considered to be normal when BPT at all sites and TBTT were within the normal limits defined in 42 healthy subjects. Patients were judged to have normal transit if >or=80% of liquid and >or=70% of viscous swallows showed normal transit. RESULTS: The following manometric diagnoses were made: normal motility (20), ineffective esophageal motility (IEM) (13), diffuse esophageal spasm (DES) (4), and achalasia (3). Abnormal transit for liquid and/or viscous boluses was found in 35.3% of patients with normal motility, in 66.7% of DES patients, and in 100% of achalasia patients. In patients with achalasia quantification of BT was often made impossible by low initial impedance baseline. Two IEM patients (15.4%) showed normal liquid and viscous transit. Swallows showing normal transit had significantly longer duration of LES relaxation in patients with normal manometry and IEM (p < 0.05). CONCLUSIONS: MII recording identifies esophageal function abnormalities in NOD patients with normal manometry, IEM, and DES. The MII technique seems to be less suitable for the most severe end of the dysphagia spectrum like achalasia.

Adult↗

PubMed2005

Recent developments in esophageal motor disorders.

PURPOSE OF REVIEW: Over the past year, further insights into the control of esophageal motility and disturbances associated with motor disorders, and additional information about the treatment of esophageal motor disorders has emerged. This review outlines the major developments in these areas. RECENT FINDINGS: The pharyngeal and esophageal phases of swallowing appear to be controlled by different areas within the vagal nuclei. Differences in the density and activation of calcium channels may explain differences in activity between the circular and clasp fibers of the lower esophageal sphincter and in the peristaltic function of the esophageal body. Tonic cholinergic input is the major determinant of esophageal tone. Experimental diabetes mellitus alters the mechanics of the esophageal body. Subtle abnormalities of peristalsis have been identified by high-resolution manometry and 24-hour ambulatory manometry that are not evident on standard manometry in patients with non-obstructive dysphagia. In achalasia, additional support has been provided for vagal damage in some patients with achalasia as well as evidence for a viral-induced immune damage to the myenteric plexus. The three main treatments for achalasia - botulinum toxin, pneumatic dilatation, and minimally invasive myotomy have been re-evaluated. Myotomy continues to provide the best results. Intraoperative manometry would seem to be a useful aid to minimize the risk of incomplete myotomy. The usefulness of glucagon in relieving food bolus obstruction has been revisited in a retrospective study. SUMMARY: These studies provide further information with which to more effectively manage esophageal motor disorders.

Animals↗

PubMed2004

Impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter function and gastroesophageal reflux in patients with reflux disease.

OBJECTIVES: Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD. METHODS: In 15 patients (7 males) with GERD (heartburn, % time esophageal pH < 4 greater than 4%, +/- history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment. RESULTS: Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p < 0.05) and basal LES pressure had increased from 4.3 +/- 2.2 mmHg to 6.2 +/- 2.1 mmHg (p < 0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0-12.1) to 7.4% (3.9-10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up. CONCLUSIONS: In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.

Adult↗

PubMed2004

Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate.

OBJECTIVES: To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate. METHODS: Thirty-eight patients, median age 68 (range 60-82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4-6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology. RESULTS: There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules. CONCLUSIONS: Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.

Aged↗

PubMed2004

Effect of hyperglycemia on triggering of transient lower esophageal sphincter relaxations.

Acute changes in blood glucose concentration have major effects on gastrointestinal motor function. Patients with diabetes mellitus have an increased prevalence of gastroesophageal reflux. Transient lower esophageal sphincter (LES) relaxation (TLESR) is the most common sphincter mechanism underlying reflux. The aim of this study was to investigate the effect of acute hyperglycemia on triggering TLESRs evoked by gastric distension in healthy volunteers. TLESRs were stimulated by pressure-controlled and volume-controlled (500 ml) gastric distension using an electronic barostat and performed on separate days. On each day, esophageal manometry was performed in the sitting position during gastric distension for 1 h under euglycemia (5 mM), and either marked hyperglycemia (15 mM) or physiological hyperglycemia (8 mM) in randomized order was maintained by a glucose clamp. Marked hyperglycemia doubled the rate of TLESRs in response to both pressure-controlled [5 (3-10.5, median or interquartile range) to 10 (9.5-14.5) per hour, P < 0.02] and volume-controlled [4 (2.5-7.5) to 10.5 (7-12.5) per hour, P < 0.02] gastric distension but had no effect on basal LES pressure. Physiological hyperglycemia had no effect on the triggering of TLESRs or basal LES pressure. In healthy human subjects, marked hyperglycemia increases the rate of TLESRs. Increase in the rate of TLESRs is independent of proximal gastric wall tension. Mechanisms underlying the effect remain to be determined. Hyperglycemia may be an important factor contributing to the increased esophageal acid exposure in patients with diabetes mellitus.

Adult↗

PubMed2003

Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation and gastroesophageal reflux in dogs.

BACKGROUND: Delivery of radiofrequency energy to the lower esophageal sphincter and gastric cardia is a new endoluminal technique proposed for the treatment of reflux disease. The mechanisms by which it achieves its effects are unclear. The study assessed the effect of radiofrequency energy delivery to the gastric cardia on the triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux in dogs. METHODS: In 13 dogs, esophageal motility and pH were measured for 1 hour after a standard liquid meal and air infusion, as well as before and 3 months after radiofrequency energy treatment. At 7 months, histologic evaluation of the gastroesophageal junction was performed. RESULTS: Radiofrequency energy delivery reduced the frequency of transient lower esophageal sphincter relaxations from 4.0 (3.0-6.75) (median [interquartile range]) per hour to 3.0 (2.0-3.0) per hour (p < 0.05). This was accompanied by a significant reduction in acid reflux episodes and esophageal acid exposure. Basal lower esophageal sphincter pressure and lower esophageal sphincter relaxation during swallowing were unchanged. There was a 63% increase in wall thickness at the gastric cardia compared with that in 2 control dogs, but no gross or histopathologic abnormalities of the esophageal or gastric mucosa. CONCLUSION: Radiofrequency energy delivery to the gastric cardia in dogs inhibits the triggering of transient lower esophageal sphincter relaxations and thereby reduces gastroesophageal reflux.

Animals↗

PubMed2003

Gastroesophageal reflux disease.

Globally, gastroesophageal reflux disease (GERD) remains a common and important clinical disorder. This review summarizes the major advances in the understanding and treatment of GERD that have been made in the past 12 months. Epidemiologic studies have yielded additional data on the clinical presentation and natural history of GERD in the East. Further insights have been presented on the pathogenesis of GERD, including the immunoregulatory environment of GERD, the neurophysiology of transient lower esophageal sphincter relaxation (TLESR), the mechanics of the esophagogastric junction as well as the influence of Helicobacter pylori. Diagnostically, a new acid exposure sensor may be a helpful cost-effective tool. Developments have been made in pharmacotherapy for TLESR. There is ongoing interest in endoscopic therapy and further developments have been made in laparoscopic fundoplication. The cost-effectiveness of several management strategies has been evaluated, aiming to reduce the cost impact of GERD on the health care system.

Journal Article↗