Search PubMed⌕ Search

Biomedical subjects

N E Schindlbeck

Publications and source records attributed to N E Schindlbeck.

At least 19 recordsLinked to original sources

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.

Anal Canal↗

[Diagnosis and clinical course in gastroesophageal reflux].

METHODS: We have previously shown, that longterm pH-monitoring is of high clinical value for the diagnosis of gastro-oesophageal reflux disease. With this method, we were able to define a sample of 166 patients with proven reflux disease. All patients had typical reflux symptoms (heartburn and/or acid regurgitation) and pathologic pH-monitoring (diurnal reflux time > 8.2% and/or nocturnal reflux time > 3.0%). They were followed up by questionnaire and interview for a mean of 41 (range: 7-86) months after diagnosis of reflux disease. RESULTS: Ten patients died of causes unrelated to reflux. In 117 (75%) of the remaining 156 patients data on the further course of the disease could be obtained. Twelve patients underwent anti-reflux surgery. Forty-one (39%) of the remaining 105 patients stopped taking medication, 13 of whom had no longer any symptoms. Sixty-four (61%) patients continued to use medication (40 as needed, 24 regularly). In comparison with baseline, symptoms were either unchanged or worse without medication in 71 patients, and better in 21. Patients with persisting symptoms during follow-up had significantly more nocturnal reflux initially (p < 0.05). The parameters oesophageal erosions at initial endoscopy, duration of reflux, age, sex, and smoking habits had no predictive value for the course of the disease. In conclusion, reflux symptoms appear to clear up spontaneously only in a minority of patients. More than half of all patients continue to use medication either as needed or regularly, with quite good results. Severe nocturnal reflux is an unfavorable prognostic factor.

Adult↗

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.

Biopsy↗

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.

Adult↗

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.

Adolescent↗

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.

Adult↗

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.

Adolescent↗

[Kidney failure as a consequence of sarcoidosis].

A 27-year-old man was admitted to hospital because of weight loss, fatigue and lack of appetite over the previous few weeks and cervical lymphadenopathy. Chest X-ray demonstrated several patchy infiltrates in both lungs. There was also evidence of progressive renal failure (creatinine concentration: 3,0 mg/dl) and hypercalcaemia (2,8 mmol/l). Bronchoalveolar lavage and renal biopsy confirmed sarcoidosis. Fundoscopy revealed eye involvement (several circumscribed, partly confluent, whitish nodules). Wegener's granulomatosis was excluded because no anticytoplasmic antibodies were demonstrated. Administration of steroids (at first daily 60 mg methylprednisolone) quickly resulted in a normal blood calcium level and normal renal function. These findings suggest that the early stage of sarcoidosis consists of in principle reversible functional changes. The differential diagnosis from systemic diseases is often difficult. If sarcoidosis is suspected one must search for rare organ manifestations so that therapy can be started as soon as possible.

Adult↗

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.

Adult↗

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.

Adolescent↗

Symptoms in gastro-oesophageal reflux disease.

Symptomatology was evaluated in 304 patients referred for 24 h oesophageal pH monitoring. Of several symptoms thought to be related to gastrooesophageal reflux disease (GORD), only heartburn (68% vs 48%) and acid regurgitation (60% vs 48%) occurred in more of the patients with GORD (as determined by pH monitoring) than of those with normal pH monitoring. When heartburn or acid regurgitation clearly dominated the patient's complaints, they had very high specificity (89% and 95%, respectively) but low sensitivity (38% and 6%) for GORD. A third of the patients reported such inconclusive symptomatology at history-taking that no preliminary diagnosis about the presence or absence of GORD could be made. In the remaining 200 patients, a clinical diagnosis by history had a sensitivity of 78% and specificity of 60%. A discriminant analysis of symptoms was inferior to a history taken by an experienced gastroenterologist.

Esophagus↗

Behavioral modification of colonic function. Can constipation be learned?

We challenged the two hypotheses: first, that defecation can be suppressed for an extended time, and second, if so, that this has an effect on upper colonic motility. Thus we studied 12 male volunteers with conditions of identical nutrition and patterns of physical activity over a two-week period, where one week with normal defecation and one week with voluntary prolonged suppression of defecation followed each other in randomized order. Frequencies of defecation, stool weights, total and segmental colonic transit times (using radiopaque markers) were compared. Frequency of defecations and stool weights were lower during suppressed defecation [8.9 +/- 0.66 vs 3.7 +/- 0.41 (mean +/- SE) bowel movements per week, P = 0.003, and 1.30 +/- 0.09 vs 0.98 +/- 0.13 kg/week, P = 0.01]. Total transit times were increased from 28.8 +/- 4.4 to 53.1 +/- 4.3 hr, P = 0.004. Segmental transit times were increased in the rectosigmoid (from 8.83 +/- 3.6 to 32.1 +/- 5.6 hr, P = 0.04) and right hemicolon (from 14.5 +/- 0.9 hr to 19.7 +/- 1.5 hr, P = 0.02) by suppression of defecation. We conclude that defecation habits may induce changes in colonic function such as those seen in constipation and that functional anorectal outlet obstruction may, probably by reflex mediation, affect the right colon.

Adaptation, Physiological↗

Esophageal 24-h pH monitoring: is prior manometry necessary for correct positioning of the electrode?

In 24-h esophageal pH monitoring, the electrode is usually positioned 5 cm above the manometrically localized esophagogastric junction. In order to replace esophageal manometry for this purpose, we tested whether the esophagogastric junction can be identified correctly by fluoroscopy or the determination of the pH-step between stomach and esophagus, compared with esophageal manometry. The distance from the nares to the esophagogastric junction was determined three times with each of the three methods in 46 patients and 14 volunteers. Fluoroscopy assumed the esophagogastric junction 1.23 +/- 0.23 cm (mean +/- SE) lower than the peak pressure point determined at manometry, pH-step only 0.45 +/- 0.16 cm. With pH-step, only one subject had a difference of more than 3 cm to the manometrically defined esophagogastric junction, whether gastroesophageal reflux disease (as proven by pH monitoring) was present or not. We conclude that the esophagogastric junction can usually be identified with sufficient accuracy by the measurement of the pH-step between stomach and esophagus. Fluoroscopy is far less accurate than pH-step, and should not be used.

Adult↗

[Measurement of colon transit time].

Several methods have been described to measure colonic transit times. The physical properties of all types of markers used allow to analyze and quantify them in stool samples or in the colon. The selective measurement of colonic (ceco-anal) transit time requires complicated intubation techniques. For most purposes it is sufficient to approximate the colonic transit by the whole gut transit, since oro-cecal transit time usually is only about a tenth of whole gut transit time. For this purpose the marker can be administered orally. In order to measure segmental colonic transit times it is necessary to monitor the distribution of the markers within the colon. For that purpose scintigraphic techniques are suited, but they require special equipment and are time consuming. Radio-opaque pellets, in contrast, are cheap, easy to handle, and have no known side effects. The following procedure is recommended: the patient swallows a gelatin capsule which contains 20 radio-opaque pellets on each of 6 consecutive days at the same time when on day seven a single abdominal x-ray is obtained. Then, segmental and total colonic transit times can be calculated from the number of retained pellets.

Carmine↗

Low fluid intake lowers stool output in healthy male volunteers.

Inadequate fluid intake is though to be one frequent cause of chronic constipation, although this has never been shown. In order to test whether fluid deprivation has an influence on colonic function, we studied eight healthy male volunteers (median age 23 y, range 21-28 y) with respect to stool frequency, stool weight and mean oroanal transit of radiopaque markers in a control week with a fluid intake of more than 2500 ml beverages per day and in a week with a fluid intake of less than 500 ml beverages per day. The two weeks followed each other in randomised order (with a wash out week in-between) and were standardised as to nutrition and physical activity. Stool frequency diminished from 6.9 +/- 0.9 to 4.9 +/- 0.3 (mean +/- SEM) defaecations per week (p = 0.041) and stool weight from 1.29 +/- 0.20 to 0.94 +/- 0.17 kg per week (p = 0.048) during fluid restriction. Mean oroanal transit times were similar in the two weeks. In conclusion, our study shows that a relatively short period of fluid deprivation decreases stool frequency and stool weight in healthy volunteers. Therefore, a low fluid intake may well be an aetiologic factor for chronic constipation in some patients and too low a fluid intake should be corrected. There is no evidence, however, that an increase of fluid intake within feasible limits has a beneficial effect on chronic constipation.

Adult↗

Relation between fasting antroduodenal motility and transpyloric fluid movements.

The effect of fasting antroduodenal motility on duodenogastric fluid movements was studied in 12 healthy volunteers. Antroduodenal motility was recorded using a multilumen manometry tube. Gastric emptying and secretion and the duodenogastric reflux of bile acids and marker were measured simultaneously by means of a marker dilution technique. Gastric emptying and acid secretion were higher in phase II than in phase I of the fasting motor activity cycle [median (range) 1.74 (1.2-4.2) ml/min vs. 0.90 (0.0-2.4) ml/min and 63.5 (6.4-115.0) vs. 37.9 (5.8-86.4) mumol/min, P less than 0.01]. The duodenogastric reflux rates of bile acids and marker were similar in all phases and showed large intra- and interindividual variations. There was no correlation between antroduodenal coordination during phase II motility and gastric emptying and duodenogastric reflux. It is concluded that the interdigestive motility pattern has moderate effects on fasting emptying of liquid gastric contents and on gastric secretion but no effects on duodenogastric reflux.

Adult↗