Paradoxical sphincter contraction is rarely indicative of anismus.

BACKGROUND: Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. AIMS: To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. METHODS: Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. RESULTS: Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p < 0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). CONCLUSIONS: Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare.

Symptoms in chronic constipation.

OBJECTIVES: This study was designed to evaluate whether detailed symptom analysis would help to identify pathophysiologic subgroups in chronic constipation. METHODS: In 190 patients with chronic constipation (age, 53 (range, 18-88) years; 85 percent of whom were women), symptom evaluation, transit time measurement (radiopaque markers), and functional rectoanal evaluation (proctoscopy, anorectal manometry, defecography) were performed. Patients were classified on the basis of objective data from all tests in four different groups ("disordered defecation," "slow gastrointestinal transit," "disordered defecation combined with slow-transit stool," and "no pathologic finding"). RESULTS: In 59 percent of patients, disordered defecation was found, and 27 percent had slow-transit stool. In 6 percent of patients, a combination of both was found; in only 8 percent of patients, there were no pathologic findings. Straining was reported by the vast majority in all groups (82-94 percent). Infrequent bowel movements and abdominal bloating were more common in slow-transit stool (87 and 82 percent vs. 69 and 55 percent, respectively; both P < 0.01). Feeling of incomplete evacuation was more common in disordered defecation (84 vs. 46 percent; P < 0.0001). However, specificity of these symptoms was discouraging (for slow-transit stool: infrequent bowel movements had a sensitivity of 87 percent and a specificity of 32 percent and abdominal bloating had a sensitivity of 82 percent and specificity of 45 percent; for disordered defecation: feeling of incomplete evacuation had a sensitivity of 84 percent and a specificity of 54 percent). Only the sense of obstruction and digital maneuvers were acceptably specific (79 and 85 percent, respectively) for disordered defecation, but sensitivity was low. CONCLUSIONS: Definition of chronic constipation by infrequent bowel movements alone is of little value; the symptom "necessity to strain" is much better suited (94 percent sensitivity). Specificity of infrequent bowel movements for slow-transit stool was discouraging. Sense of obstruction and digital manipulation for evacuation are relatively specific for disordered defecation but insensitive. Therefore, symptoms of chronically constipated patients are not well suited to differentiate between the pathophysiologic subgroups suffering chronic constipation.

Clinical response to dietary fiber treatment of chronic constipation.

OBJECTIVES: To determine the clinical outcome of dietary fiber therapy in patients with chronic constipation. METHODS: One hundred, forty-nine patients with chronic constipation (age 53 yr, range 18-81 yr, 84% women) at two gastroenterology departments in Munich, Germany, were treated with Plantago ovata seeds, 15-30 g/day, for a period of at least 6 wk. Repeated symptom evaluation, oroanal transit time measurement (radiopaque markers), and functional rectoanal evaluation (proctoscopy, manometry, defecography) were performed. Patients were classified on the basis of the result of dietary fiber treatment: no effect, n = 84; improved, n = 33; and symptom free, n = 32. RESULTS: Eighty percent of patients with slow transit and 63% of patients with a disorder of defecation did not respond to dietary fiber treatment, whereas 85% of patients without a pathological finding improved or became symptom free. CONCLUSION: Slow GI transit and/or a disorder of defecation may explain a poor outcome of dietary fiber therapy in patients with chronic constipation. A dietary fiber trial should be conducted before technical investigations, which are indicated only if the dietary fiber trial fails.

Decreased substance P levels in rectal biopsies from patients with slow transit constipation.

OBJECTIVE: Previous studies in patients with chronic constipation found abnormalities in the nervous tissue of the large intestine, predominantly in the muscularis externa. Since there is evidence that the nervous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation. DESIGN AND METHODS: Twenty-two patients (17 females, 5 males) with chronic slow transit constipation (oro-anal transit with radio-opaque markers on high fibre diet > 70 h) and long-term use of laxatives, and 20 controls (12 females, 8 males) with no history of constipation, were included in this study. Large rectal biopsy specimens including the submucosa were obtained from 5 cm above the dentate line and frozen in liquid nitrogen. After microdissection of the biopsies into mucosa and submucosa the neuropeptides were extracted by boiling and homogenizing the tissue in acetic acid and determined using validated radioimmunoassays. RESULTS: Patients with slow transit constipation showed, compared to healthy controls, significantly lower levels of the excitatory neurotransmitter substance P in the mucosa and submucosa of rectal biopsies. There was no difference between the two groups concerning the levels of the inhibitory neurotransmitters, VIP and somatostatin. CONCLUSION: Slow transit constipation is associated with abnormalities of the substance P content of the enteric nervous system of mucosa and submucosa. This seems not to be related to chronic laxative use, since anthranoids cause a reduction in the levels of inhibitory neurotransmitters (VIP, somatostatin), but not of substance P, in the rat colon.

Diagnostic value of histology in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: In the absence of oesophageal erosions longterm pH monitoring is the present gold standard for diagnosing gastro-oesophageal reflux disease (GORD). This method, however, is invasive, time consuming, expensive, and not generally available. AIMS: As histological changes have been described in GORD, this study looked at the possibility of whether the diagnosis of non-erosive reflux disease could be made by histological examination routinely during endoscopy. SUBJECTS: A total of 24 prospectively selected patients with symptoms suggestive of GORD and seven healthy volunteers. METHODS: Oesophageal erosions and other peptic lesions were excluded by oesophago-gastroduodenoscopy. Oesophageal pinch biopsy specimens were taken 2 cm and 5 cm above the oesophagogastric junction and evaluated blindly for the histological parameters cellular infiltration, basal zone hyperplasia, and papillary length. Twenty four hour pH monitoring was used as gold standard for the definition of reflux disease. It was abnormal in 13 patients (reflux patients) and normal in 11 patients (symptomatic controls) and in seven healthy volunteers. RESULTS: Sparse infiltration of the epithelium with lymphocytes in at least one biopsy specimen was found in all patients and volunteers, with neutrophils in three reflux patients, and with eosinophils in two reflux patients and in two healthy volunteers. The basal zone thickness was increased in three reflux patients, in one symptomatic control, and in one healthy volunteer. The papillary length was greater than two thirds of total epithelium in six of 13 reflux patients in contrast with none in 11 symptomatic controls (p < 0.05) and to one healthy volunteer. The sensitivity of the parameter papillary length hence was only 46%. CONCLUSIONS: Although gastro-oesophageal reflux produces slight histological changes apart from oesophageal erosions in a few subjects, none of the established histological parameters can fulfil the for the diagnosis of GORD in patients without visible oesophageal erosions.

Functional diagnostic work-up in patients with irritable bowel syndrome.

The first aim of the study was to find a cause of symptoms in patients suffering from "irritable bowel syndrome" using diagnostic tests aimed at functional disorders of lower gut. A second aim was to test, whether the presence of irritable bowel syndrome (or, synonymously, absence of classic organic disease) can be predicted by specific symptoms. 134 consecutive patients (50 +/- 16 SD years, range 17 to 88, 94 women) presenting in our gastroenterological outpatient department with abdominal pain and altered bowel habits were included. A conventional diagnostic work-up aimed at classic organic diseases and, if negative, a functional diagnostic work-up aimed at gastrointestinal malfunction such as dietary fibre trial, functional proctoscopy, defecography, colonic transit of radiopaque markers, anorectal manometry, and lactose tolerance test were done. A classic organic disease was found in only 15 of 134 patients by conventional diagnostic tests. Functional diagnostic work-up yielded a diagnosis in 70 of the remaining 119 patients that else would have been labeled to suffer from IBS (25 slow transit constipation, 20 disordered defecation, nine low fibre intake, and nine lactose intolerance among them). When symptoms were evaluated with a standardized questionnaire, "constipation" and the "necessity of straining to open bowels" were very specific for functional bowel disorder (92% and 100%), but sensitivity of both symptoms was only about 60%. The so-called "Manning criteria" had a very low prevalence in our sample and so were not discriminatory. Since in more than half of the patients with "irritable bowel syndrome" a specific diagnosis can be reached, functional tests should be considered in such patients. The symptom "constipation" in patients with lower gut complaints predicted a functional disorder rather than a classic organic disease with a high specificity.

Empiric therapy for gastroesophageal reflux disease.

BACKGROUND: In the absence of highly specific symptoms and without esophageal erosions, long-term pH monitoring is necessary for diagnosing gastroesophageal reflux disease. This method, however, is not generally available. OBJECTIVE: To determine whether gastroesophageal reflux disease can be diagnosed empirically by acid suppression in patients with normal results of endoscopy. METHODS: We studied 33 consecutive outpatients with pathologic findings on pH monitoring who had symptoms compatible with gastroesophageal reflux disease and normal results of esophagogastroduodenoscopy, particularly a normal appearance of the esophageal mucosa. The severity of symptoms was graded on a visual analog scale from 1 to 10 by the patient. The patients were treated for at least 7 days with either ranitidine, 150 mg twice daily (patients 1 through 10), omeprazole, 40 mg/d (patients 11 through 21), or omeprazole, 40 mg twice daily (patients 22 through 33). A reassessment of symptoms and second pH monitoring were performed during the last day of treatment. RESULTS: Omeprazole, 40 mg/d, significantly reduced the severity of symptoms from 7.1 (range, 4 to 9) to 3.7 (0 to 8) and the reflux measure mean acidity from 0.98 mmol/L (0.21 to 76 mmol/L) to 0.02 mmol/L (0 to 0.47 mmol/L). Omeprazole, 40 mg twice daily, significantly reduced the severity of symptoms from 6.8 (3 to 10) to 0.6 (0 to 2) and the mean acidity from 0.38 mmol/L (0.13 to 8.5 mmol/L) to 0.01 mmol/L (0 to 0.14 mmol/L). Both doses of omeprazole were superior to ranitidine, 150 mg twice daily. When a 75% reduction of symptoms was defined as positive, the "omeprazole test" with 40 mg twice daily had a sensitivity of 83.3%, whereas the sensitivity with 40 mg/d was only 27.2%. CONCLUSION: In practice, the diagnosis of gastroesophageal reflux disease can be ruled out if symptoms do not improve with a limited course of high-dose proton pump inhibitors.

The influence of arginine-vasopressin on stool output and gastrointestinal transit time in healthy volunteers.

OBJECTIVE: It was asked whether continuous infusion of arginine-vasopressin (AVP) could decrease stool output and gastrointestinal transit time in healthy volunteers. DESIGN: Randomised single blind cross-over-design. SUBJECTS: 5 healthy male volunteers. INTERVENTIONS: Continuous s.c. infusion of AVP (7.5 micrograms/d) for one week vs. 0.9% NaCl-solution (placebo). Some days before the experiment started, the volunteers underwent a two-day-thirsting-period (< 500 ml/day). MEASUREMENTS: AVP-levels in serum, urine output, AVP-urine-excretion, stool frequency, stool weight, colonic transit time. RESULTS: As compared to saline infusion both serum-levels of AVP and AVP-excretion in urine were about four times higher during AVP-infusion whereas they were doubled during thirsting. Accordingly urine output was lower when AVP-levels were high. Parameters of colonic motility did not differ significantly (stool frequency 6.8 +/- 0.8/week for placebo vs. 6.8 +/- 0.5/week during AVP, stool weight 200.3 +/- 25.0 g/d vs. 210.6 +/- 21.1 gld, total colonic transit 22.9 +/- 7.0 hours vs. 25.7 +/- 5.8 hours). CONCLUSION: 1. AVP is well absorbed when applied subcutaneously. 2. AVP in the dosage given has no major influence on stool output and gastrointestinal transit time in healthy volunteers.

Polyethylene glycol 4000 for slow transit constipation.

Slow transit constipation is notoriously difficult to treat. We tested whether polyethylene glycole 4000 (PEG) improves slow transit constipation. Eight female outpatients with symptoms of constipation and a colonic marker transit of more than 60 h were included (age 46 +/- 4y, duration of complaints 17 +/- 3y) in a randomised controlled cross-over study. During a 6-week placebo and 6-week PEG-phase (60g PEG/d) the following parameters were measured: 1. subjective well-being with respect to defeacation on a visual analogue scale (-8 cm very bad, +8 cm very good), 2. in the first 5 weeks of each phase, average dose of sodium picosulfate (prescribed as only allowed laxans, dose adjusted and protocolled on a diary by patient) 3. stool frequency, 4. colonic transit of radiopague polythene pellets in the last week of each phase (the use of laxative was strictly prohibited in this last week). Both subjective and objective parameters of colonic function improved significantly. Visual analog scale ratings improved from -4.65, [-8; 0.5] to 4.65, [-8; 7.5]cm (median, range) (p = 0.028), the self-administered dose of sodium picosulfate decreased from 4, [0; 37] to 0, [0; 11] drops per day (p = 0.028), stool frequency increased from 3.1, [1; 30] to 11, [2; 33] defeacations per week (p = 0.017), and total colonic transit decreased from 91, [67; 116] to 43 h, [17; 76]h (p = 0.017). In conclusion, PEG improves colonic function in patients with slow transit constipation subjectively and objectively. PEG should be considered as an additional option in patients refractory to established forms of treatment.

Interobserver agreement in defecography.

PURPOSE: This study was designed to test the reproducibility of the diagnostic assessment of defecographies in patients with a suspected disorder of defecation. METHODS: To evaluate interobserver agreement, 100 defecographic series of patients with complaints suggesting a disordered defecation were evaluated independently by three observers with a standardized questionnaire. After six weeks, a random sample of 35 of 100 defecographies was evaluated a second time with clinical data provided (history, proctologic examination). To evaluate whether the position of residual volume in the rectum would affect agreement, patients with substantial retention either in the upper or lower rectum were also evaluated separately. RESULTS: Total agreement regarding rectocele and internal prolapse was 0.81 and 0.75, respectively (1.0 = complete agreement), and was significantly higher than chance agreement. Total agreement regarding residual volume in the rectum at the end of defecography and clinical relevance of findings was not different from chance agreement, providing clinical data did not significantly improve agreement. When residual volume was situated in the lower rectum, agreement regarding incompleteness of emptying and its clinical relevance was much better (0.93). CONCLUSIONS: Interobserver agreement is good regarding the deformation of the rectum during defecography but not different from chance agreement regarding the completeness of evacuation.

How effective is nonlaxative treatment of constipation?

In almost any textbook of medicine so-called simple measures are proposed for treating constipation, such as increasing physical activity, drinking more fluid, triggering the gastrocolonic response by, e.g., drinking a glass of water or a cup of coffee, and bowel training. All of these have not been formally evaluated in constipated patients. Biofeedback training is useful for paradoxical puborectal contraction ('anismus'). Dietary fibre, e.g. in the form of wheat bran, increases stool weight and decreases colonic transit time. So every patient should have an empiric treatment with an adequate amount of fibre. Some patients, especially those with slow transit constipation and those with stasis in the right hemicolon, are not likely to respond to a therapy with bran, however.

Body acupuncture: effect on colonic function in chronic constipation.

Acupuncture has been claimed to be an efficacious treatment for chronic constipation, though there are no studies to prove this. We therefore investigated the effect of body acupuncture on stool frequency and colonic transit time of radiopaque markers in 8 constipated patients (58 +/- 6 years, 3 female; vigorous straining necessary to open bowels without the use of laxatives for more than one year, total colonic marker transit > 60 h) in a control period and during a three weeks treatment period with six sessions. Acupuncture was performed as body acupuncture with electric needles (10 Hz, current titrated to individual threshold, 25 min each session) on acupuncture points Di4 [He Gu], Ma25 [Tian Shu], Le3 [Yuan], and B125 [Da Chang Yu]). Two patients dropped out during acupuncture because symptoms of constipation worsened. In the other 6 patients, stool frequencies and colonic transit times were not significantly different during control and acupuncture period (0.38 +/- 0.09 vs. 0.40 +/- 0.14 defecations per day +/- s.e.m., 95% confidence interval for the difference control minus acupuncture [-0.34; 0.30], and 97 +/- 17 vs. 108 +/- 24h, 95% Cl [-50; 27]). Segmental transit times for right and left hemicolon, and rectosigmoid colon did not differ significantly either. In conclusion, acupuncture as performed in this study does not influence objective parameters of colonic function to a clinically relevant degree.

[Smoking and gastrointestinal function]. / Rauchen und gastrointestinale Funktion.

Aspects of gastrointestinal function pathogenetically related to peptic ulcer have been studied extensively. Even as to secretion of gastric acid and pancreatic bicarbonate a definite statement concerning the impact of smoking is difficult. Most of the available studies found that smoking increases acid secretion and decreases pancreatic secretion. This may, at least in part, explain the untoward effect of smoking in ulcer disease. Gastric emptying is slightly decreased by smoking. Gastro-oesophageal and duodenogastric reflux are obviously not influenced to a clinically relevant extent. With regard to the colon, we did not retrieve any relevant publications. In summary, in patients with ulcer disease there is one good reason more to discourage from smoking.

What is behind dyspepsia?

The first aim of the present study was to determine the cause of dyspepsia after negative conventional diagnostic work-up. In such patients, an extended diagnostic work-up was performed including esophageal pH monitoring and manometry, gastric and hepatobiliary scintigraphy, and lactose tolerance test. In 88 of 220 dyspeptic patients (mean age 49 years, range 17-87; 114 women) presenting to our gastroenterological outpatient department, a cause for dyspepsia was found by conventional work-up. Thirty-one of the remaining patients did not enter extended work-up because of minor symptoms. In 47 of 101 patients entering extended work-up, a diagnosis was established (21 endoscopy-negative gastroesophageal reflux disease, 11 gastric stasis, 6 biliary dyskinesia, and 5 lactase deficiency among them). A second aim of the study was to determine whether clusters of symptoms such as "gastroesophageal reflux-like," "dysmotility-like," and "dyspepsia of unknown origin" reliably predict the groups of diseases suggested by these terms. This was not the case. In conclusion, in 40% of dyspeptic patients, a conventional diagnostic work-up led to a diagnosis that explained a patient's symptoms. After a negative conventional diagnostic work-up, an extended diagnostic work-up with functional tests yielded a possible explanation for their symptoms in 47% of patients. In such patients symptomatology was of little help for predicting the diagnosis.

Three year follow up of patients with gastrooesophageal reflux disease.

Data on the natural course of gastrooesophageal reflux disease are sparse. One hundred and sixty six patients with typical reflux symptoms (heartburn and/or acid regurgitation) and pathologic pH monitoring (reflux time > 8.2% upright and/or > 3.0% supine) were studied. The patients were followed up by questionnaire and interview for a mean of 41 (seven to 86) months after diagnosis of reflux disease. Ten patients had died of diseases not reflux related. In 117 (75%) of the remaining 156 patients data on the course of gastrooesophageal reflux disease could be obtained. In 12 patients anti reflux surgery had been performed. Forty one (39%) of the remaining 105 patients have stopped taking medical therapy, in 13 of these patients symptoms had completely disappeared. Sixty four patients continued on medication (40 on demand, 24 regularly). When asked how their symptoms would be if they completely stopped medication, 71 patients considered their symptoms to be equal or worse and 21 patients to be improved as compared with the initial investigation. Patients with persisting symptoms at follow up had significantly more supine reflux (p < 0.05) at the initial pH monitoring as compared with patients with improved symptoms. The presence and grade of oesophageal erosions at initial endoscopy, duration of symptoms, age, sex, and smoking habits had no influence on the course of gastrooesophageal reflux disease. In conclusion, reflux symptoms disappear only in a minority of patients with proven gastrooesophageal reflux disease. More than half of all patients continue medication, either on demand or regularly. Severe supine reflux is an unfavourable prognostic factor.

Simultaneous assessment of bolus transport and contraction parameters in multiple-swallow investigations.

A better understanding of scintigraphic findings may lead to a wider acceptance of esophageal transit studies. The purpose of this study, therefore, was to correlate standard manometric parameters with the quantitative and qualitative characteristics of liquid and semi-solid bolus transport. Twenty-nine patients were simultaneously investigated with esophageal scintigraphy and manometry. Single-swallow and sum-image data of six consecutive swallows were analyzed. No significant relationship between transit time and the velocity of the peristaltic wave could be identified, which suggests that factors other than peristaltic velocity (e.g., pharyngeal pump) essentially modulate esophageal transit. There was also no linear correlation between esophageal emptying and peristaltic amplitudes. Emptying was normal in patients with amplitudes greater than 30 mmHg and reduced in those with amplitudes less than 30 mmHg. This suggests that a threshold pressure greater than 30 mmHg is necessary to propel a test bolus adequately. Patterns in condensed images have been shown to specifically reflect the events in corresponding manometric recordings. Normal and different pathologic types of peristalsis presented analogous findings in both modalities. Thus, an analysis of the relationship between bolus transport and contraction parameters in simultaneous studies increases understanding of quantitative and qualitative scintigraphic results.

Abdominal wall massage: effect on colonic function in healthy volunteers and in patients with chronic constipation.

Colonic massage has been claimed to be an efficacious treatment for chronic constipation, though there are no studies to prove this. We therefore investigated the effect of abdominal wall massage on stool frequency and colonic transit time of radiopaque markers in 9 constipated patients (68 +/- 5 years, 5 female, colonic transit greater than 60 h) and in 7 healthy male volunteers (27 +/- 1.2 years) in a control phase and during a three week treatment phase with 9 sessions. Massage was performed as propulsive abdominal wall massage along the presumed course of the colon in an aboral direction (each session 20 min). Stool frequency did not change significantly from control to massage, neither in patients [0.59 +/- 0.08 to 0.68 +/- 0.09 defaecations per day, 95% CI control-massage (-0.23; 0.04)] nor in healthy volunteers 1.11 +/- 0.11 to 0.86 +/- 0.13, 95% CI (-0.01; 0.53)]. Total colonic transit times remained similar during the control and massage phase in patients (126 +/- 19 and 111 +/- 17 h, 95% CI (-11; 41)] and in healthy volunteers (40 +/- 7 and 38 +/- 6 h, 95% CI (-8; 13)]. Even when patients and healthy volunteers were statistically evaluated together, control and massage did not differ significantly. In patients, scores of well-being and stool consistency did not differ significantly during control and massage periods. So colonic massage does not change parameters of colonic function to a clinically relevant degree in healthy volunteers and constipated patients of the investigated age-groups.

Which pH threshold is best in esophageal pH monitoring?

Two questions were examined, namely, 1) whether pH 4 is really the optimal threshold for the definition of acid gastroesophageal reflux, and 2) to what extent shifting of the upper limits of normal affects sensitivity and specificity of 24-h pH monitoring. To answer these questions, we studied 74 patients with proven reflux disease and 37 asymptomatic volunteers, using ambulatory 24-h esophageal pH monitoring. Gastroesophageal reflux was defined as episodes with esophageal pH of less than the threshold values 3.0, 3.5, 4.0, 4.5, or 5.0, respectively. For each of these pH thresholds, the percentage time with esophageal pH below the threshold was calculated separately for periods of upright and supine body position. Two-dimensional receiver-operating-characteristic (ROC) analysis was used to define upper limits of normal. A maximum of sensitivity, specificity, and rate of correct decisions (all 89%) was obtained using pH 4 for the definition of gastroesophageal reflux, although other pH thresholds were not much worse. On the basis of pH 4, the upper limits of normal could be shifted around the "optimal upper limit of normal" within a certain limit without considerable loss of accuracy of pH monitoring. This may explain the divergences between upper limits of normal obtained by different laboratories. In conclusion, 1) the threshold pH 4 should further be used for the definition of acid gastroesophageal reflux, and, 2) within certain limits, shifting of the upper limits of normal has little effect on the accuracy of pH monitoring in gastroesophageal reflux disease.