Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China

Esophageal transit scintigraphy seems to be a valid methodology to assess impaired esophageal motility in early stages of disease. The purpose of this study was to discriminate patients with primary Raynaud's phenomenon (RP) and patients with systemic sclerosis (SSc) from healthy subjects by esophageal scintigraphy with a semisolid meal. METHODS: We studied 32 patients with primary RP, 18 with SSc and 13 healthy subjects. Dysphagia, acid regurgitation and heartburn were scored. After an overnight fast, all subjects underwent esophageal scintigraphy, using a semisolid orally ingested bolus (10 mL apple puree) labeled with 99mTc-sulfur colloid. Esophageal transit and emptying time and integral value were evaluated with the subjects in the upright (sitting) and supine positions. Transit time was defined as the time from the entry of 50% of radioactivity into the upper esophagus until the clearance of 50% of the bolus from the whole esophagus. Emptying time was defined as the time from the entry of 50% of radioactivity into the upper esophagus, until the clearance of 100% of the bolus from the whole esophagus. Integral value was defined as the total counts under the time-activity curve normalized to the maximum. RESULTS: Esophageal transit and emptying time and integral value, evaluated in both positions, were significantly higher in patients with SSc than in healthy subjects and than in patients with RP. Moreover, patients with RP had all three parameters, assessed in supine position, significantly longer compared to healthy subjects. Clinical scores regarding dysphagia, acid regurgitation and heartburn were not significantly different between patients with RP and SSc. CONCLUSION: Esophageal transit and emptying time and integral value appear to be able to discriminate patients with primary RP from patients with SSc and patients with RP from healthy subjects, suggesting an early mild esophageal dysfunction in RP.     

Barrett's esophagus. Clinical review of 26 cases

Barrett's esophagus was diagnosed in 26 men in a five-year period by demonstrating esophageal specialized columnar epithelium in target biopsies obtained at endoscopy or in peroral suction biopsies of the esophageal mucosa. The clinical, radiologic and manometric features of these patients were reviewed retrospectively. Esophageal lesions associated with this epithelium included distal and midesophageal strictures and ulcers, alone or in combination, or simply esophagitis. One patient had an associated adenocarcinoma. Twenty of 26 (77%) had heartburn or regurgitation, 16 (62%) had easily elicited reflux of barium while supine and 16 of 17 tested had lower esophageal sphincter pressure in the incompetent range. Ninety-six percent had one or more of these parameters positive. This series demonstrates a wide spectrum of esophageal lesions in Barrett's esophagus, and supports the concept that this lesion occurs as a consequence of gastroesophageal reflux and erosive esophagitis. The case of adenocarcinoma in this series adds to the concern that the columnar lined lower esophagus may be a premalignant lesion.     

How familial is familial tremor? The genetic epidemiology of essential tremor

BACKGROUND & AIMS: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium. METHODS: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal-appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient. RESULTS: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls. CONCLUSIONS: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Pyloric muscle in asymptomatic infants: sonographic evaluation and discrimination from idiopathic hypertrophic pyloric stenosis

Nissen fundoplication is now the most common antireflux operation for gastroesophageal reflux disease. This study is a report on the laparoscopically performed floppy Nissen procedure. Two hundred consecutive patients were analyzed (84 women, 116 men, mean age 49 years, mean duration of symptoms 5 years) after laparoscopic Nissen fundoplication between 1992 and 1996. The main indications for surgery were daily heartburn, retrosternal pain, and regurgitation demanding continuous medical therapy. Eight patients (4%) had esophageal stricture, and 21 (11%) had Barrett's esophagus with intestinal metaplasia. All patients underwent upper gastrointestinal endoscopy, 24-h esophageal pH monitoring, and esophageal manometry before and 3 months after the operation. In addition, a questionnaire was completed an average of 2.2 years (range 1.0-4.6) after the operation. The results of the study were as follows: mortality was zero, and the morbidity rate was 5%. The mean hospital stay was 3.8 +/- 2.8 days, and sick leave was 14.3 +/- 10.4 days. Postoperatively, esophagitis was healed or significantly improved in all but 4 patients (98%), and 24-h pH and lower esophageal sphincter pressure were normal. After 2 years, 87% of the patients had Visick scores of I-II. It is concluded that laparoscopic floppy Nissen fundoplication provides an efficient and safe alternative for surgical treatment of gastroesophageal reflux disease.     

Esophageal dysfunction in syndrome X

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.     

Symptomatic gastroesophageal reflux: incidence and precipitating factors

The incidence and precipitating factors associated with symptomatic gastroesophageal reflux were evaluated by a questionnaire in 446 hospitalized and 558 nonhospitalized subjects. Of 385 control subjects 7% experienced heartburn daily, 14% noted heartburn weekly, and 15% experienced it once a month, giving a total of 36% of subjects having heartburn at least monthly. Daily heartburn occurred at a significantly greater (P less than 0.05) rate for 246 medical inpatients (14%) and for 121 patients seen in outpatient gastroenterological clinic (15%). Pregnant women seen in uncomplicated obstetrical clinic had symptoms of significantly greater (P less than 0.01) incidence: daily (25%) and at least once monthly (52%). Age, sex, or hospitalization did not significantly affect incidence. Fried foods, "spicy" foods, and alcohol were the most common precipitating factors.     

Self-medication of dyspepsia: how appropriate is it?

BACKGROUND: The scope of self-medication is increasing in many countries, and drugs for dyspepsia are a popular group for deregulative activities. This study investigated what kind of upper gastrointestinal symptoms people self-medicate and how appropriate this self-medication is. METHODS: An anonymous questionnaire was give to 50 consecutive customers buying antacids, alginates, or sucralfates in 10 pharmacies in the capital area in Finland in 1995. In half of the pharmacies the questionnaire was returned by mail, and in the other half the questionnaire was filled out at the pharmacy. The response rate was 53% (n = 292). RESULTS: The commonest reasons for self-medication were heartburn (88%), gastrointestinal pain (31%), and acid regurgitation (32%). Seventy-five per cent of respondents had used dyspepsia drugs for more than a year. The commonest way to self-medicate was to interchange regular and occasional use. Knowledge about the proper use of dyspepsia drugs was poor, and 6% of respondents had symptoms contraindicating self-medication but had not visited a physician during the past year. Patients more than 60 years old were especially at risk of potential inappropriate use. CONCLUSIONS: Over-the-counter (OTC) drugs for dyspepsia are likely to be used improperly. A physician's advice on the use of OTC dyspepsia drugs, in addition to detailed printed information about drug action and proper administration, would be important means to guarantee appropriate use of these drugs.     

Identification and characterization of cerebral cortical response to esophageal mucosal acid exposure and distention

BACKGROUND & AIMS: Esophageal acid exposure is a common occurrence in healthy individuals and patients with esophagitis. Clinically, perception of this exposure ranges from no perception to severe heartburn and chest pain. Cerebral cortical response to esophageal mucosal contact to acid has not been systematically studied. The aim of this study was to elucidate cerebral cortical response to esophageal acid exposure in normal individuals by functional magnetic resonance imaging (FMRI). METHODS: We studied 10 normal healthy volunteers. Cortical FMRI response to 10 minutes of intraesophageal perfusion of 0.1N HCl (1 mL/min) was determined, and the results were compared with those of saline infusion and balloon distention. RESULTS: Acid perfusion did not induce heartburn or chest pain but increased FMRI signal intensity by 6.7% +/- 2.0% over the preperfusion values. No increase was detected for saline infusion. FMRI signal intensity to balloon distention was similar to that of acid perfusion. Activation latency, activation to peak, and the deactivation periods for response to acid perfusion were significantly longer than those of balloon distention (P < 0.05). CONCLUSIONS: Contact of esophageal mucosa with acid, before inducing heartburn, evokes a cerebral cortical response detectable by FMRI. Temporal characteristics of this response are significantly different from those induced by esophageal balloon distention.     

Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells

Patients admitted acutely to hospital may be at risk of increased morbidity and mortality as a result of gastroesophageal reflux and its complications. The recognized association of gastroesophageal reflux with cardiac and respiratory disease, the use of drugs that reduce lower esophageal sphincter pressure, and the supine position in which many patients are nursed may increase the risk of gastroesophageal reflux. This study aimed to determine the prevalence and severity of refluxlike symptoms in a series of consecutive unselected patients admitted acutely through the accident and emergency department of a district general hospital and to study the effect of hospitalization on these symptoms. Patients were interviewed by questionnaire on two occasions: immediately following admission and again 7-10 days later. The frequency of symptoms of heartburn, acid regurgitation, dysphagia, nausea, and belching were recorded on a 6-point scale, in addition to whether these symptoms occurred at night. Medication history, the number of days spent on bed rest, nasogastric intubation, and operation history were also recorded. In all, 275 patients were interviewed, of whom 229 had a second interview; 27% (62) had symptoms at least once a week (49% reported symptoms at least once a month) prior to admission, of whom 4% (9) had daily heartburn and/or acid regurgitation. Following admission to hospital there was a significant (P < 0.001) fall in the prevalence and frequency of refluxlike symptoms. There was a significant association of refluxlike symptoms with number of days spent in bed (P < 0.05) and with the use of nonsteroidal antiinflammatory drugs in hospital (P < 0.0001). Logistic regression analysis confirmed the association of NSAIDs with refluxlike symptoms. Nasogastric intubation and surgery were not associated with heartburn. In conclusion, symptoms of heartburn and acid regurgitation become less frequent following admission to hospital. This probably relates to a reduction in physical exertion following hospital admission but may reflect a reduction in anxiety levels or treatment of underlying disease. Patients on prolonged bed rest and those given non-steroidal anti-inflammatory drugs are at increased risk of refluxlike symptoms and may require antireflux measures.     

Laparoscopic Toupet fundoplication for gastroesophageal reflux disease with poor esophageal body motility

Impaired esophageal body motility is a complication of chronic gastroesophageal reflux disease (GERD). In patients with this disease, a 360-degree fundoplication may result in severe postoperative dysphagia. Forty-six patients with GERD who had a weak lower esophageal sphincter pressure and a positive acid reflux score associated with impaired esophageal body peristalsis in the distal esophagus (amplitude <30 mm Hg and >10% simultaneous or interrupted waves) were selected to undergo laparoscopic Toupet fundoplication. They were compared with 16 similar patients with poor esophageal body function who underwent Nissen fundoplication. The patients who underwent Toupet fundoplication had less dysphagia than those who had the Nissen procedure (9% vs.44%; P=0.0041). Twenty-four-hour ambulatory pH monitoring and esophageal manometry were repeated in 31 Toupet patients 6 months after surgery. Percentage of time of esophageal exposure to pH <4.0, DeMeester reflux score, lower esophageal pressure, intra-abdominal length, vector volume, and distal esophageal amplitude all improved significantly after surgery. Ninety-one percent of patients were free of reflux symptoms. The laparoscopic Toupet fundoplication provides an effective antireflux barrier according to manometric, pH, and symptom criteria. It avoids potential postoperative dysphagia in patients with weak esophageal peristalsis and results in improved esophageal body function 6 months after surgery.     

Gastrointestinal hemorrhage in patients with systemic sclerosis and CREST syndrome

OBJECTIVES: Systemic sclerosis (SSc) and calcinosis, Raynaud's phenomenon, esophageal disease, sclerodactyly, telangiectasia (CREST) syndrome present distinctive microvasculature lesions that are thought to be responsible for tissue damage and disease progression. Involvement of the gastrointestinal tract may lead to the occurrence of profuse hemorrhage. We performed a study to assess the incidence and characteristics of gastrointestinal hemorrhage in a large group of patients with SSc and CREST syndrome. METHODS: We reviewed the medical records of 144 patients with SSc/CREST seen at our institution during the period 1985-1996. Endoscopic findings and clinical data were correlated. Data are expressed as means +/- SD. RESULTS: Twenty-two of 144 (15.2%) patients had at least one episode of gastrointestinal hemorrhage (16 women, 6 men; mean age, 59.4 +/- 17.6 yr). Eight patients (8/22; 36%) had multiple episodes and four (4/22; 18%) required chronic transfusion therapy. Mucosal telangiectasias were the most common cause of bleeding (9/22; 40.9%), followed by peptic ulcer disease (7/22; 31.8%) and erosive gastritis (3/22; 13.6%). Bleeding telangiectasias occurred in the entire gastrointestinal tract, including oral cavity (n = 1), esophagus (n = 1), stomach (n = 3), duodenum (n = 1), ileum (n = 1), cecum (n = 2), and colon (n = 2). Mortality was 22.7% in patients with gastrointestinal bleeding, compared with 7.3% in patients without bleeding. CONCLUSIONS: Patients with SSc/CREST syndrome are at risk of developing severe gastrointestinal hemorrhage. This complication is associated with frequent hospitalization, blood transfusions, and increased mortality. Mucosal telangiectasias are the most common source of bleeding. Appropriate endoscopic intervention is recommended in evaluating and preventing bleeding in patients with SSc/CREST.     

Carcinoma of the esophagus and esophagogastric junction: sensitivity of radiographic diagnosis

OBJECTIVE: The purpose of this study was to determine the sensitivity of barium studies in revealing carcinoma of the esophagus and esophagogastric junction. MATERIALS AND METHODS: We retrospectively reviewed 50 cases of squamous cell carcinoma of the esophagus (n = 25) and adenocarcinoma of the esophagus (n = 14) or esophagogastric junction (n = 11) in which double-contrast (n = 46) or single-contrast (n = 4) barium studies had been done. The original radiology reports were reviewed to determine whether the lesions had been seen on barium studies and whether cancer had been diagnosed. Records were also reviewed to determine the number of patients who underwent esophageal endoscopy because of findings suggestive of cancer on barium studies at some point from January 1992 through December 1992. Pathology records were then reviewed to determine the number of true- and false-positive barium studies during this same period. RESULTS: Lesions were shown on barium studies in 49 (98%) of 50 patients, and carcinoma of the esophagus or esophagogastric junction was diagnosed or suspected in 48 patients (96%). In a separate part of the study, we found that endoscopy had been recommended to rule out malignant tumor in only 26 (1%) of 2484 patients who underwent barium studies at some point from January 1992 through December 1992. Endoscopy revealed cancer in 11 of those 26 patients; the remaining 15 were assumed to have false-positive radiologic examinations. Barium studies therefore had a positive predictive value of 42%. CONCLUSION: The double-contrast barium study is a sensitive technique for the diagnosis of carcinoma of the esophagus and esophagogastric junction. This high sensitivity can be achieved while recommending endoscopy in only about 1% of all patients who undergo barium studies.     

Effect of pneumatic dilation on gastroesophageal reflux in achalasia

The aims of this study were to assess the effect of pneumatic dilation on gastroesophageal reflux in achalasia, differentiate esophageal acid due to lactate from acid due to gastroesophageal reflux, and determine if chest pain and heartburn are reliable indicators of gastroesophageal reflux. Eight untreated achalasia patients underwent pre- and postdilation esophageal fluid/food residue lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom assessment. All patients had a successful clinical outcome and a decrease in lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients before and two patients after dilation. Postdilation acid exposure was mild. Lactate was detected before dilation in all patients. A lactate concentration >2 mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile. There was no correlation between an abnormal 24-hr pH test and age, lower esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare in untreated achalasia and esophageal acidity may result from ingestion of acidic foods or production of lactate. Mild gastroesophageal reflux occurs after dilation but is of no clinical significance. Chest pain and heartburn are not indicators of acid reflux in achalasia.     

Thrombolysis with i.v. recombinant human tissue-type plasminogen activator in patients with bypass graft occlusion: a good adjunctive therapeutic mode (preliminary and case reports)

OBJECTIVES: To determine the incidence of gastroesophageal reflux in patients with subglottic stenosis (SGS) and to determine if upper esophageal reflux occurs in addition to lower esophageal reflux in these patients. DESIGN: Esophageal pH probe studies were reviewed in patients diagnosed as having SGS. SETTING: A tertiary care pediatric medical center. PATIENTS: All patients diagnosed as having SGS between January 1990 and July 1996 who had undergone monitoring with an overnight esophageal pH probe. Seventy-four patients qualified for the study. All 74 patients underwent lower probe testing, and 55 of the 74 underwent dual (upper and lower) probe testing. MAIN OUTCOME MEASURES: The percent of time a pH measurement of less than 4.0 was recorded in the upper and lower esophagus. A lower probe pH measurement of less than 4.0 more than 10% of the study time was considered high risk for developing reflux-associated pathologic symptoms. A lower probe pH measurement of less than 4.0 for 5% to 10% of the study time was considered a marginal risk for developing reflux-associated pathologic symptoms. Upper probe criteria for reflux-associated symptoms have not been established. Therefore, patients were grouped as having a pH of less than 4.0 in the upper esophagus for 0%, 0.1% to 0.9%, 1.0% to 1.9%, 2.0% to 3.0%, or more than 3% of the study time. RESULTS: Thirty-seven of the 74 patients who underwent lower probe testing had a pH of less than 4.0 more than 5% of the study time, and 24 had a pH of less than 4.0 more than 10% of the study time. Twelve of the 55 patients who underwent upper probe testing had no measurable reflux; 27 of the 55 had a pH of less than 4.0 more than 1% of the study time; 14 had a pH of less than 4.0 more than 2% of the study time, and 11 had a pH of less than 4.0 more than 3% of the study time. CONCLUSIONS: Gastroesophageal reflux is frequently present in patients with SGS. Gastric contents frequently reach the upper and lower esophagus in these patients. In addition, the high incidence of gastroesophageal reflux in these patients suggests that it may play a role in the development of SGS. The possible effect of gastroesophageal reflux on the surgical repair of SGS requires further study.     

Evaluation by a randomized trial of the usefulness of endoscopy after treatment of a flare-up of non-severe esophagitis

OBJECTIVES: The clinical usefulness of esophageal endoscopy at the end of a treatment of non-severe esophagitis due to gastro-esophageal reflux is unknown. The aim of this randomized trial was to compare two strategies for the management of non-severe esophagitis, one with endoscopy at the end of the initial treatment including a retreatment of persistent ulcerations (group 1) and one without final endoscopy (group 2). PATIENTS AND METHODS: Eligible patients had heartburn and endoscopically proved esophagitis, non-confluent or confluent erosions and must have been relieved of their heartburn after a 4 to 6 week treatment with H2 blockers or by proton pump inhibitor. When the ulcerations were healed in group 1 and immediately at the end of the initial treatment in group 2, a self-care treatment by sodium alginate was prescribed. A total of 369 patients were randomized, 178 in group 1, 191 in group 2. RESULTS: At 6 months, there was no difference in the percentage of patients with clinical and endoscopical success, 52% and 55% in group 1 versus 47% and 60% in group 2 respectively. In group 1, 29 patients (16%) needed another treatment than alginate versus 31 patients in group 2 (16%, NS). Among patients with endoscopy at 6 months, the percentage of patients with confluent erosions was 4% (5/140) and with non-confluent erosion 26% (37/140) in group 1 versus 6% (9/158) and 22% (34/158) in group 2 respectively (NS). The percentage of patients with at least one sick day related to reflux was 12% in group 1 versus 5% in group 2 (P = 0.03). There was no difference in pharmacy costs (331,40 vs 264,3 Francs). CONCLUSION: Endoscopic verification is not necessary in patients with non-severe esophagitis who have been clinically improved by an initial treatment by H2 blockers or proton pump inhibitor, even among patients with confluent esophageal erosions.     

Effect of hyperparathyroidism and hypercalcemia on lower esophageal sphincter pressure

Heartburn is a frequent and sometimes initial complaint in hyperparathyroidism, and it is often relieved by successful parathyroid surgery. Four of five patients with primary hyperparathyroidism and heartburn obtained relief of symptoms and had an increase in lower esophageal sphincter pressure after successful operative treatment. Four of five volunteers undergoing calcium infusion exhibited a decrease in lower esophageal sphincter pressure after about 2.5 to 3 hours of infusion. Calcium infusion in a treated patient who had an increase in lower esophageal sphincter pressure postoperatively resulted in a transient return of lower esophageal sphincter pressure to preoperative levels.     

Esophageal manometry in the opossum

The opossum esophagus is commonly used as an animal model of the human esophagus. We used esophageal manometry in normal animals to provide basal data about normal esophageal motor functions in vivo in this species. At rest, separate and distinct high pressure zones can be recorded at the level of the lower esophageal sphincter, diaphragmatic hiatus, aortic arch, and upper esophageal sphincter. Each zone demonstrates a characteristic pattern of pressures in the radii of the coronal section and a characteristic response to swallowing. The hiatal and aortic zones can be mistaken for the esophageal sphincters. Pressures in the sphincters fall with swallowing. Peristalsis is not bolus-dependent and occurs with 98% of swallows. Pressures generated by peristalsis are greater in the middle of the esophagus than at the ends. Values for resting lower esophageal sphincter pressure and the characteristics of peristalsis were reproducible between different studies in the same animals.     

No relationship between carbohydrate intake and effect of acarbose on HbA1c or gastrointestinal symptoms in type 2 diabetic subjects consuming 30-60% of energy from carbohydrate

OBJECTIVE: To determine the relationship between carbohydrate intake and the effect of acarbose on HbA1c in subjects with type 2 diabetes treated with acarbose alone, acarbose plus sulfonylurea, acarbose plus metformin, or acarbose plus insulin. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized placebo-controlled study in which subjects with diabetes in four treatment strata (77 on diet alone, 83 treated with metformin, 103 treated with sulfonylurea, and 91 treated with insulin) were randomized to treatment with placebo or acarbose for 12 months. Before randomization, and 3, 6, 9, and 12 months after randomization, fasting blood was obtained for HbA1c, and 3-day diet records were collected. Subjects who completed at least 6 months of acarbose therapy and provided at least three 3-day diet records were included. RESULTS: In the 114 subjects included in this analysis, carbohydrate intake varied from approximately 30-60% of energy There was no significant relationship between carbohydrate intake and change in HbA1c in any of the four treatment strata (diet: n=26, r=0.35, P=0.076; metformin: n=27, r=0.26, P=0.19; sulfonylurea: n=35, r=0.24, P=0.16; insulin: n=25, r=-0.27, P=0.19). In the 80 subjects consuming <50% of energy from carbohydrate, the fall in HbA1c (7.83 +/-0.17% at baseline to 6.72+/-0.13% on acarbose, P < 0.001) was no different from that of the 34 subjects consuming >50% of energy from carbohydrate (7.55+/-0.25% at baseline to 6.66+/-0.23% on acarbose, P < 0.001). There was no difference in carbohydrate intake between those who dropped out of the study because of gastrointestinal side effects and those who did not, and there was no relationship between severity of symptoms and the composition of the diet. CONCLUSIONS: In subjects with type 2 diabetes consuming 30-60% of energy from carbohydrate, the effect of acarbose on HbA1c and gastrointestinal symptoms was not related to carbohydrate intake. Because most people consume at least 30% of energy from carbohydrate, we conclude that no special diet is needed for acarbose to be effective in improving blood glucose control in the treatment of type 2 diabetes.