Variables influencing parental perception of inherited metabolic diseases before and after genetic counselling

BACKGROUND: Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. AIM: To report the clinical and laboratory features of patients with gastroesophageal reflux. PATIENTS AND METHODS: Five hundred thirty-four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. RESULTS: There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. CONCLUSIONS: Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations.     

Design and synthesis of small semi-mimetic peptides with immunomodulatory activity based on myelin basic protein (MBP)

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett's esophagus, but clinical studies in patients with adenocarcinoma arising in Barrett's esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatic volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett's esophagus, and 14 patients with early adenocarcinoma arising in Barrett's esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopic Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett's esophagus and was highest in patients with early carcinoma in Barrett's esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett's esophagus and 11 (78.6%) of 14 patients with early adenocarcinoma in Barrett's esophagus. Nissen fundoplication but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett's esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone.     

Oesophageal acid clearance in patients with severe reflux oesophagitis

Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease.     

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, in fact, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.     

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.     

Esophagitis in Sprague-Dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.     

Recognition of a 31,000 molecular weight protein synthesized by the mussel Mytilus galloprovincialis Lmk. during Dinophysis spp. algal bloom in the Gulf of Trieste (upper Adriatic Sea)

OBJECTIVES: To demonstrate gastroesophageal reflux induced by proximal gastrectomy and to report preventive measures, such as total gastrectomy followed by Roux-en-Y esophagojejunostomy. METHODS: Thirteen patients underwent proximal gastrectomy (PG), and six patients underwent total gastrectomy (TG). Two of the 13 patients who received PG later underwent completion total gastrectomy. All patients were followed with endoscopy, radionuclide scintigraphy, and 24-h pH monitoring. RESULTS: Endoscopic examination revealed evidence of esophagitis in all PG group patients; however, none of the TG group had esophagitis. Prolonged esophageal transit was observed in 11 patients (10 in the PG group, one in the TG group). Increased residual fraction was found in 10 patients (nine in the PG group, one in the TG group). An increase in the retrograde index was found in 14 cases (11 in the PG group, three in the TG group). Positive enterogastroesophageal reflux was identified in 11 patients (eight in the PG group, three in the TG group). Twenty-four hour pH monitoring resulted in 10 positives (10 in the PG group, none in the TG group). CONCLUSIONS: Frequently, proximal gastrectomy will lead to significant gastroesophageal reflux and, subsequently, to varying degrees of esophagitis. The clinical symptoms are usually characteristic. However, the severity of esophagitis and the mechanism of reflux can be determined only by integrated interpretation of a reflux study. The study should include endoscopy, radionuclide scintigraphy, and 24-h pH monitoring. Although a total gastrectomy with Roux-en-Y diversion can reduce the incidence of acid reflux, neutral enteroesophageal reflux may be observed during a radioactive isotope study. Fortunately, neutral refluxes rarely cause esophagitis. A proximal gastrectomy should be avoided in adenocarcinoma of the gastric cardia, except in early cancer. Symptomatic palliation can be relieved by medication. However, completion total gastrectomy is the only effective method for eradicating unrelenting symptoms.     

Omeprazole as a diagnostic tool in gastroesophageal reflux disease

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.     

Leprosy patients with lepromatous disease recognize cross-reactive T cell epitopes in the Mycobacterium leprae 10-kD antigen

BACKGROUND: Cough associated with gastroesophageal reflux (GER) may originate in extrathoracic airway receptors made hypersensitive by acid-induced mucosal injury. OBJECTIVE: We investigated the role of laryngeal disease and dysfunction in the pathogenesis of GER-associated cough in nonasthmatic patients. METHODS: Seven patients with GER-associated cough were compared with 7 patients with GER but no cough. The patients underwent fiberoptic endoscopy for assessment of laryngitis and esophagitis (expressed by scores); esophageal manometry; 24-hour pH monitoring; lung function tests; and histamine inhalation challenge with assessment of bronchial threshold (concentration provoking 10% fall in FEV1 [PC10]), extrathoracic airway threshold (concentration provoking 25% fall in the maximal midinspiratory flow [PC25MIF50]), and cough threshold (concentration provoking 5 or more coughs PCcough). The patients were reevaluated after 3 months of medical treatment for GER. RESULTS: Patients with cough, compared with those without cough, had significantly higher laryngitis scores (P = .002), lower esophageal sphincter pressures, longer time with pH below 4 (P = .003), greater number of episodes of reflux longer than 5 minutes (P = .016), longer esophageal clearance time (P = .048), and significantly lower PC25MIF50 (P = .005) and PCcough (P = .008) values. Laryngitis score was significantly inversely related to either PCcough (P < .001) or PC25MIF50 (P <.01) but not to PC10. Laryngitis score, PC25MIF50, and PCcough were all closely related to GER severity. After GER treatment, laryngitis, PC25MIF50, and PCcough were all significantly improved. CONCLUSIONS: These findings suggest that GER-associated cough is strongly associated with laryngeal disease and dysfunction consequent to acid reflux injury in nonasthmatic patients.     

Physiology and biophysics in electrocardiography

Simultaneous esophageal and gastric manometry and intraesophageal pH monitoring were performed in 12 patients with gastroesophageal reflux diseases in order to compare the frequency and mechanism of reflux in upright and supine postures. It was found that there was no differences in the number of reflux episodes, acid clearance time and percentage time of pH below 4 (P > 0.05). Frequency of reflux associated with lower esophageal sphinter relaxation (LESR) and gastric press increase was similar in two postures (P > 0.05). The results suggest that upright reflux may be as important as supine reflux in the development of reflux esophagitis. The main machanism of reflux in the two postures is LESR. Increase of gastric press may be a factor leading to gastroesophageal reflux.     

Double-blind crossover study of ranitidine and ebrotidine in gastro-esophageal reflux disease

Gastroesophageal reflux disease (GERD) is multifactorial disorder in which acid exposure has a central role in the mucosal damage, and the mainstay of medical treatment is the suppression of gastric acid secretion justifying the use of H2 receptors antagonists. In our study we compared the effects of ranitidine and ebrotidine, a novel H2 antagonist with gastroprotective properties, on the motor, pH and endoscopic aspects of GERD in randomized cross-over trial in humans. Twenty patients with endoscopic evidence of erosive esophagitis were included in the study. Esophageal manometry and 24-hour pH-metry were done with the use Synectics (Sweden) systems. The same examinations were repeated after 20 days period of treatment with either ranitidine or ebrotidine, given in single dose 300 and 800 mg (nocte) respectively. The pressure within the lower esophageal sphincter (LES) in the untreated and treated with ebrotidine or ranitidine patients remained lowered. Patients with GERD showed increase in duration and decrease in amplitude and propagation of peristaltic waves in the esophageal body which were not improved after treatment. Complete healing after 40 days of treatment was comparable with ebrotidine and ranitidine and averaged about 40%. The pH-metry showed improvement in treated patients in the reflux frequency and time pH below 4, ranitidine being more effective than ebrotidine. It can be concluded that GERD patients showed weaker primary peristalsis unrelated to LES pressure and treatment. Treatment with ebrotidine or ranitidine reduced significantly the endoscopic and self-assessment score, ebrotidine and ranitidine being equally effective in healing of esophageal mucosal lesions.     

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.     

pH-metric analysis after successful antireflux surgery: comparison of 24-hour pH profiles in patients undergoing floppy fundoplication or Roux-en-Y duodenal diversion

Fundoplication is the most widely used antireflux method, whereas Roux-en-Y duodenal diversion (partial gastrectomy, vagotomy, and Roux-en-Y reconstruction) has been used in fewer patients with more complicated gastroesophageal reflux disease. Abnormal esophageal pH values are normalized after successful fundoplication. However, very little is known about possible changes in the pH profile after successful Roux-en-Y duodenal diversion. A total of 37 patients with severe gastroesophageal reflux disease were treated by fundoplication (n=22) or Roux-en-Y duodenal diversion (n=15). Postoperatively all patients in both groups were symptom free and healing of esophagitis was verified endoscopically. After fundoplication, the 24-hour esophageal acid exposure decreased significantly (P=0.03) and the pH profile normalized (pH<4 in 5.8%+/-2.4% of the recorded time). However, the decrease in esophageal acid exposure was not significant (P=0.77) after successful Roux-en-Y reconstruction and the pH profile remained abnormal (pH<4 in 15.1%+/-4.3%). It was concluded that 24-hour esophageal pH monitoring is a reliable means of assessing the results of fundoplication, but the current test criteria should be reexamined in evaluating the results of Roux-en-Y duodenal diversion. Healing of esophagitis after Roux-en-Y duodenal diversion despite abnormal acid reflux, as shown by 24-hour pH measurements, suggests that duodenal contents also have a role in the pathogenesis of esophagitis in an acid milieu.     

Are frequent short gastro-oesophageal reflux episodes the cause of symptoms in patients with non-ulcer dyspepsia responding to treatment with ranitidine?

BACKGROUND: Patients with non-ulcer dyspepsia (NUD) responding to treatment with H2-receptor antagonists have no clinically useful characteristics. This trial compares the gastro-oesophageal reflux pattern as measured by 24-h oesophageal pH monitoring in patients responding to ranitidine with that of non-responders. METHODS: Thirty-one patients with NUD were randomized to 6 weeks' double-blind alternating treatment with 150 mg ranitidine twice daily or placebo and classified as responders or non-responders. RESULTS: Pathologic gastro-oesophageal reflux was seen in 3 of the 13 responders and 4 of the 18 no-responders (NS). The responders had frequent short reflux episodes (< 1 min in duration). When 4 patients with > or = 5 reflux episodes longer than 5 min were excluded, the number of short reflux episodes (median) in responders and non-responders was 32 and 14, respectively. The difference is statistically significant (p = 0.025). There were no other differences between the groups. CONCLUSIONS: In this study patients with NUD responding to ranitidine were characterized by frequent short reflux episodes in the absence of numerous long reflux episodes.     

Nissen fundoplication for reflux esophagitis. Long-term clinical and endoscopic results in 109 of 127 consecutive patients

OBJECTIVE: This study evaluates the clinical and endoscopic long-term results of Nissen fundoplication in reflux esophagitis. SUMMARY BACKGROUND DATA: Nissen fundoplication has been reported to give good results in the treatment of gastroesophageal reflux with success rates up to 78-97%. Most of the previous studies on long-term results of fundoplication have, however, been based on interviews with only sporadic endoscopic examinations. METHODS: Of 127 patients consecutively treated with Nissen fundoplication for reflux esophagitis, 109 were available for follow-up after a median of 77 months. Upper gastrointestinal endoscopy was done in 105 cases, and all the patients with reflux symptoms or abnormal endoscopic observations were referred to esophageal 24-hour pH monitoring and manometry. RESULTS: No symptoms of gastroesophageal reflux were reported by 73 of the 109 patients, but dysphagia was present in 47. Endoscopy showed defective fundic wrap in 24 patients. Objective evidence of reflux was found in 24 patients (endoscopic esophagitis in 18 and pathologic 24-hour pH score without esophagitis in 6). Esophagitis was found in 14 of the 24 patients with defective wrap, but in only 4 of the 81 with infact wrap. CONCLUSIONS: Nissen fundoplication alleviated symptoms of gastroesophageal reflux and cured esophagitis in great majority of cases. The main determinant of outcome was the state of the fundic wrap.     

Clinical applications of esophageal manometry and pH monitoring

In summary, GERD patients are usually well managed using a careful medical history, endoscopy, and empirical trials of antireflux medications. Extended esophageal pH monitoring is unnecessary in most patients but can be of considerable value in managing patients with typical or atypical symptoms who are refractory to standard therapy for GERD. Furthermore, the test can be useful in documenting abnormal reflux in an individual without esophagitis being evaluated for antireflux surgery. The test is done with compact, portable data loggers, miniature pH electrodes, and computerized data analysis. The pH electrode should be positioned 5 cm above the manometrically defined upper limit of the LES, and patients should undergo the test on an unrestricted diet. In terms of data analysis, the total percentage time of pH < 4 provides as much information as any other scheme of quantifying esophageal acid exposure, but symptom association is essential when evaluating atypical or sporadic symptoms. Enthusiasm for 24-h pH monitoring must, however, be tempered with an analysis of its proven clinical utility in patient management with its utility rightfully compared with that of an empirical trial of anti-reflux therapy. Ambulatory pH monitoring is probably most useful in examining patients without typical reflux symptoms or patients who have either partially or completely failed a trial of anti-reflux therapy. To date, there have not been any prospective, controlled clinical trials evaluating these uses. Suggested clinical indications for ambulatory pH monitoring are listed in Table 5 (53).     

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.     

A randomized controlled trial of two methods for collection of sterile urine in neonates

The cause of laryngeal and pharyngeal carcinomas is likely multifactorial. Smoking is an important factor, but mucosal damage from gastroesophageal reflux may also contribute. The purpose of this study was to determine whether gastroesophageal reflux is more common in patients with laryngeal or pharyngeal carcinomas than in those without these malignancies. Over an 8-year period, we correlated the results of clinical and radiographic examinations of the pharynx and esophagus to pH monitoring results in 798 patients with a variety of upper aerodigestive tract symptoms and who underwent both pH monitoring and barium esophagography. In this group, 63 patients (52 men, 11 women) had laryngeal or pharyngeal carcinomas, and 735 patients (319 men, 416 women) had neither malignancy. Abnormal pH findings were defined as a total percentage of esophageal acid exposure time of 6% or more as determined with the esophageal probe, or any reflux event detected with the pharyngeal probe. Thirty-four of 63 patients with carcinomas (54%) had abnormal pH-monitoring results: Esophageal acid exposure was abnormal in 10 patients, pharyngeal acid exposure was abnormal in 7 patients, and acid exposure was abnormal in both areas in 17 patients. Of the 735 patients without malignancies, 365 (50%) had abnormal pH-monitoring results (p > 0.05). In this population of patients, abnormal results of pH monitoring were common, occurring in 399 (50%) of 798 patients, but no significant difference was found between results in those with and without laryngeal or pharyngeal carcinomas. Therefore, our study found that gastroesophageal reflux as shown by pH monitoring was not more common in patients with these malignancies.     

Exclusion of the meal period improves the clinical reliability of esophageal pH monitoring

Meal period exclusion from 24-h pH testing allows better separation between controls and patients with gastroesophageal reflux disease. We reviewed the results of 24-h pH studies of 350 patients with reflux symptoms. They were divided into two groups based on the 95th percentile of the total percentage of time when pH was < 4 for healthy persons in our laboratory. Thus group A consisted of 212 patients with symptoms and normal acid exposure and group B consisted of 138 patients with symptoms and abnormal acid exposure. The change in upright reflux excluding the meal period was calculated for each patient. Meal period exclusion resulted in opposite effects for the two groups of patients, with a change in median upright reflux of -0.6% for group A and +0.5% for group B (p < 0.0001). After meal exclusion, five patients were reclassified as having reflux, with four (80%) of these responding to antireflux therapy. Nine other patients were recategorized as not having reflux after meal exclusion. Only one of seven patients (14%) for whom data were available responded to treatment (two patients were lost to follow-up). We recommend meal period exclusion from pH analysis because it improves the clinical reliability of esophageal pH monitoring.     

The molecular pathology of urological malignancies

BACKGROUND: Effective esophageal peristalsis is a major determinant of esophageal clearance function. The relation of esophageal body function with a mechanically defective lower esophageal sphincter and the development of esophageal mucosal injury in patients with gastroesophageal reflux disease is unclear. STUDY DESIGN: We analyzed the relations among the manometrically determined esophageal clearance function, lower esophageal sphincter dysfunction, esophageal acid exposure, and the presence and severity of esophageal mucosal injury in patients with gastroesophageal reflux disease. Normal values for the manometric assessment of esophageal clearance function were established in 50 normal volunteers and subsequently applied to 160 symptomatic patients with increased esophageal exposure to gastric juice and various grades of esophageal mucosal injury (no minimal surgery, esophagitis, stricture, and Barrett's esophagus). RESULTS: Defective clearance function was present in 47.5% of the patients; a defective lower esophageal sphincter was documented in 63.1%. Compromised esophageal clearance function was significantly more common in patients with a defective lower esophageal sphincter than in those with normal sphincter function (55% versus 33.8%). Esophageal acid exposure time and the prevalence and severity of esophageal mucosal injury were highest in patients with a defective sphincter and compromised clearance function. CONCLUSIONS: These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be due to persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. This may influence the choice and outcome of antireflux surgery. Surgical correction of a mechanically defective sphincter before the loss of esophageal body function is advocated.