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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 37 records · Page 2Linked to original sources
PubMed2002

Dose-dependent control of intragastric pH by pantoprazole, 10, 20 or 40 mg, in healthy volunteers.

BACKGROUND: Proton pump inhibitors have emerged as the most effective class of drugs for the treatment of gastro-oesophageal reflux. Pantoprazole is a proton pump inhibitor that has demonstrated high clinical efficacy. AIM: To evaluate the effect of once-daily doses of pantoprazole, 10, 20 and 40 mg, on gastric acidity in healthy volunteers. METHODS: Thirty-six subjects received pantoprazole in a three-way crossover design study. Ambulatory 24-h intragastric pH and distal oesophageal pH were monitored at baseline and on the last day of each treatment period. The measured endpoints were the median intragastric and oesophageal pH, the percentage of time the intragastric pH < 4 and oesophageal pH < 4 and the area under the curve for gastric acidity over 24 h. Safety was evaluated by incidence and severity of adverse events. RESULTS: Pantoprazole demonstrated a linear dose- dependent suppression of gastric acidity over the dose range 10-40 mg. The dose of 40 mg demonstrated a significantly greater response than the lower doses, particularly at night. All pantoprazole doses were well tolerated. CONCLUSIONS: Pantoprazole demonstrates a dose-related effect in the range 10-40 mg once daily. The once-daily dose of 40 mg provides the highest and most consistent control of gastric pH, especially at night.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Combined multichannel intraluminal impedance and pH-metry: an evolving technique to measure type and proximal extent of gastroesophageal reflux.

The accepted "gold standard" for measuring gastroesophageal reflux (GER), distal esophageal pH recording, has limited ability to measure nonacid GER, a potentially important cause of symptoms, in an era of potent acid-suppressing medications. A combination of multichannel intraluminal impedance (MII) and pH- metry offers an advantage over pH measurement alone. MII can detect GER at multiple levels of the esophagus independent of pH. In addition, use of MII enables refined characterization of intraluminal events, including presence, type (air, liquid, or mixed), and spaciotemporal characterization of a bolus. MII has the potential to become a useful clinical tool to assess ongoing reflux in patients on acid-suppression therapy.

Electric Impedance↗
PubMed2001

Repetitive proximal esophageal contractions: a new manometric finding and a possible further link between Parkinson's disease and achalasia.

Repetitive, spontaneous contractions of the proximal esophagus have recently been identified as a feature of achalasia. This article documents similar findings in six patients with Parkinson's disease. Parkinson's disease and achalasia share many common features neurologically. Both have Lewy bodies in the esophageal myenteric plexuses and the substantia nigra, in addition to evidence of degeneration of the dorsal motor nucleus of the vagus. The esophageal features radiologically and manometrically are also similar. Repetitive proximal esophageal contractions may represent another link between these diseases. They have also been reported in scleroderma. We speculate that the common link between all three disease processes may be poor distensibility of the esophagus.

Aged↗
PubMed2001

Maximal acid reflux control for Barrett's oesophagus: feasible and effective.

UNLABELLED: The treatment of patients with Barrett's oesophagus is controversial. Debate exists regarding the use and value of high dose acid suppression as the standard of practice. Despite prolonged use of high dose proton pump inhibitors (40 mg omeprazole, 60 mg lansoprazole), most studies have shown no convincing evidence of significant regression of Barrett's length. These studies, however, have used fixed doses of proton pump inhibitors and did not regularly document control of oesophageal acid exposure. AIM: To determine whether regression of Barrett's epithelium can be achieved with documented maximal acid suppression. METHODS: We have prospectively followed nine patients with Barrett's oesophagus (eight male; mean age 60 years) for more than 1 year. They were all treated using medical therapy with pH monitoring documenting oesophageal acid exposure over 24 h < 1.6% of the time, and with two or more esophagogastroduodenoscopies performed by the same endoscopist. RESULTS: Acid control was individually tailored and achieved with proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) and ranitidine at bedtime (HS) (Ran) if necessary. All nine patients (100%) showed some evidence of regression. All nine patients (100%) showed a decrease in Barrett's length (mean 2 cm, range 1-3 cm). Six out of nine (66.67%) patients showed evidence of squamous islands on the last oesophagogastroduodenoscopy. The mean total distal oesophageal acid exposure was 0.38% (range: 0-1.5%). The mean follow-up of patients was 54 months (range: 13-118 months). CONCLUSIONS: Consistent and individually tailored maximal acid suppression documented by pH-metry is achievable and may result in decreased length and development of squamous islands in patients with Barrett's epithelium. This approach should be further evaluated as potentially the preferred medical treatment for these patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mg.

BACKGROUND: Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity. AIM: To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control. METHODS: Study I: 12 Helicobacter pylori-negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24-h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean +/- s.d. RESULTS: (1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night-time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 +/- 19% vs. 48 +/- 14%, P < 0.001), and night-time periods (34 +/- 21% vs. 26 +/- 14%, P < 0.05). (3) A large inter-subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 +/- 18% vs. 51 +/- 15%, P=0.015) than omeprazole 20 mg. CONCLUSION: These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Bedtime H2 blockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors.

AIM: Proton pump inhibitors taken twice daily before meals (proton pump inhibitor b.d. AC) effectively controls daytime gastric pH; however, nocturnal gastric acid breakthrough (NAB) occurs in more than 75% of patients. Adding an H2-blocker at bedtime decreases NAB in normal subjects. The efficacy of this regimen has not been evaluated in GERD patients. The aim of this study was to assess the effects of proton pump inhibitor b.d., both with and without bedtime H2-blocker on intragastric pH and the occurrence of NAB in GERD patients. METHODS: Prolonged ambulatory pH studies in GERD patients were reviewed. Group A: 60 patients (mean age 53 years, male 30) taking either omeprazole 20 mg or lansoprazole 30 mg b.d. Group B: 45 patients (mean age 49 years, male 23) on proton pump inhibitor b.d. (omeprazole 20 mg or lansoprazole 30 mg) plus an H2-blocker at bedtime (ranitidine 300 mg, famotidine 40 mg or nizatidine 300 mg). Eleven patients were evaluated during treatment with both regimens (group C). The percentage time of nocturnal and daytime intragastric pH > 4 and per cent of patients with gastric NAB were analysed. In the patients with NAB, its duration and associated oesophageal acid exposure also were analysed. RESULTS: Median percentage time intragastric pH > 4 overnight was 51% in group A, compared to 96% in group B (P < 0.0001). Median percentage daytime pH > 4 was 73% in group A and 79.8% in group B (P=0.14). Median percentage time intragastric pH >p 4 overnight increased from 54.6% without H2RA to 96.5% after adding bedtime H2RA (P=0.0013) in group C patients. NAB occurred in 82% patients in group A and 40% in group B (P < 0.0001). The mean duration of oesophageal acid exposure during NAB was significantly shorter in group B (18 +/- 6 min) than in group A (42 +/- 9 min, P=0.04). SUMMARY: Adding a bedtime H2-blocker to the treatment enhanced nocturnal gastric pH control and decreased NAB compared to the proton pump inhibitor b.d. regimen. A bedtime H2-blocker also decreased oesophageal acid exposure during NAB. CONCLUSION: Adding a bedtime H2-blocker to a proton pump inhibitor b.d. regimen should be considered in patients who require continued nocturnal gastric acid control whilst taking proton pump inhibitor b.d.

Anti-Ulcer Agents↗
PubMed2001

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.

Aged↗
PubMed2001

Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole.

BACKGROUND & AIMS: Nonacid reflux may explain symptoms in acid-suppressed patients. Simultaneous intraesophageal impedance and pH measurement was used to evaluate the frequencies of postprandial acid and nonacid reflux before and after omeprazole administration. METHODS: Twelve heartburn patients underwent two 2-hour studies of intraesophageal impedance and pH in the right lateral decubitus position after a refluxogenic meal; session 1 without medication, session 2 after 7 days of omeprazole twice daily. Acid and nonacid reflux were quantified. RESULTS: Two hundred seventeen reflux episodes were detected before and 261 after omeprazole treatment (P > 0.05). Percentage of acid reflux decreased (from 45% to 3%, P = 0.02) and nonacid reflux increased (from 55% to 97%, P = 0.03) after omeprazole. Heartburn and acid taste were more commonly linked to acid reflux but were also produced by nonacid reflux. Regurgitation was reported equally in acid and nonacid reflux. Delta(pH) > 1 did not help predict the presence of symptoms during nonacid reflux. CONCLUSIONS: During treatment with omeprazole, postprandial reflux becomes predominantly nonacid. Symptoms are more common with acid reflux but are also produced by nonacid reflux. Simultaneous intraesophageal impedance and pH may be useful in evaluating the role of nonacid reflux in symptoms that persist despite adequate acid suppression.

Adult↗
PubMed2001

Radiofrequency energy delivery to the gastroesophageal junction for the treatment of GERD.

BACKGROUND: In this multi-center study, the feasibility, safety, and efficacy of radiofrequency (RF) energy delivery to the gastroesophageal junction (GEJ) for the treatment of gastroesophageal reflux disease (GERD) were investigated. METHODS: Forty-seven patients with classic symptoms of GERD (heartburn and/or regurgitation), a daily anti-secretory medication requirement, and at least partial symptom response to drugs were enrolled. All patients had pathologic esophageal acid exposure by 24-hour pH study, a 2 cm or smaller hiatal hernia, grade 2 or less esophagitis, and no significant dysmotility or dysphagia. RF energy was delivered with a catheter and thermocouple-controlled generator to create submucosal thermal lesions in the muscle of the GEJ. GERD symptoms and quality of life were assessed at 0, 1, 4, and 6 months with the short-form health survey (SF-36). Anti-secretory medications were withdrawn 7 days before each assessment of symptoms and pH/motility study. Medication use, endoscopic findings, esophageal acid exposure, and motility were assessed at 0 and 6 months. RESULTS: Thirty-two men and 15 women underwent treatment. At 6 months there were improvements in the median heartburn score (4 to 1, p < or = 0.0001), GERD score (26 to 7, p < or = 0.0001), satisfaction (1 to 4, p < or = 0.0001), mental SF-36 (46.2 to 55.5, p = 0.01), physical SF-36 (41.1 to 51.9, p < or = 0.0001), and esophageal acid exposure (11.7% to 4.8%, p < or = 0.0001). Esophagitis was present in 25 patients before treatment (15 grade 1 and 10 grade 2) and 8 had esophagitis at 6 months (4 grade 1 and 4 grade 2, p = 0.005). At 6 months, 87% no longer required proton pump inhibitor medication. There was no significant change in median lower esophageal sphincter pressure (14.0 to 12.0 mm Hg, p = 0.19), peristaltic amplitude (64 to 66 mm Hg, p = 0.71), or lower esophageal sphincter length (3.0 to 3.0, p = 0.28). There were 3 self-limited complications (fever for 24 hours, odynophagia lasting for 5 days, and a linear mucosal injury that was healed after 3 weeks). CONCLUSION: RF energy delivery significantly improved GERD symptoms, quality of life, and esophageal acid exposure while eliminating the need for anti-secretory medication in the majority of patients with a heterogeneous spectrum of clinical disease severity but with minimal active esophagitis or hiatal hernia.

Adult↗
PubMed2001

Medical, surgical, and endoscopic treatment of gastroesophageal reflux disease and Barrett's esophagus.

Over the past decade, medical and surgical approaches to the patient with gastroesophageal reflux disease (GERD) have improved dramatically. Proton pump inhibitors have become the dominant medical therapy because of their high efficacy and safety. Laparoscopic surgical approaches have improved concomitantly with the advances in medical therapy, resulting in the perception that either continuous medical therapy or surgery are appropriate options for long-term maintenance of this chronic disorder. Recent approval of new endoscopic treatments for GERD has generated considerable interest, but acceptance of these techniques should be limited by the small number of patients studied to date, the lack of placebo controls, and the short duration of follow-up.

Anti-Ulcer Agents↗
PubMed2001

Effect of age on differences in upper esophageal sphincter and pharynx pressures between patients with dysphagia and control subjects.

OBJECTIVES: The aim of this study was to explore the effect of age and food consistency on manometric data of the swallow sequence in patients with dysphagia. METHODS: Manometric data from 41 patients (age range, 32-88 yr) and 41 age-matched control subjects was examined for differences between subgroups < 60 yr and > or = 60 yr of age, as well as for changes with food consistency. RESULTS: Only pharynx peak pressure showed an age-dependent decrease (144.1 +/- 21.4 mm Hg vs 95.8 +/- 15.1 mm Hg, p < 0.05) in patients. Significant higher upper esophageal sphincter residual pressure and delayed onset of upper esophageal sphincter relaxation were noted in patients aged <60 yr compared to age-matched controls, whereas only pharynx peak pressure was significantly lower in patients compared to controls aged > or = 60 yr. Food consistency did not have a consistent effect on manometric results in patients with dysphagia. CONCLUSIONS: This is the first study to systematically explore the influence of age and food consistency on manometric parameters in dysphagia patients. These results may provide useful insights when identifying actual manometric abnormalities in patients with dysphagia. They also suggest possible different underlying mechanisms of dysphagia in younger versus older patients.

Adult↗
PubMed2001

Classification of oesophageal motility abnormalities.

Manometric examination of the oesophagus frequently reveals abnormalities whose cause is unknown and whose physiological importance is not clear. A large body of literature dealing with oesophageal motility abnormalities has evolved over the past few decades but comparisons among studies have been compromised by the lack of a widely accepted system for classifying the abnormal motility patterns, and by the lack of uniform diagnostic criteria for the putative disorders. Based on an extensive review and analysis of the literature, this report suggests an operational scheme to be used for the general classification of oesophageal motility abnormalities, and proposes standardised manometric criteria for the putative oesophageal motility disorders. By applying the guidelines proposed in this report, clinicians and researchers can determine if their patients fulfil the manometric criteria for a putative motility disorder. This should facilitate and improve comparisons among patients and studies. However, it is important to emphasise that fulfilment of the proposed criteria does not establish the clinical importance of the motility abnormalities.

Adult↗
PubMed2001

Esophageal function testing using multichannel intraluminal impedance.

Multichannel intraluminal impedance (MII) is a new technique for evaluation of bolus transport. We evaluated esophageal function using bolus transport time (BTT) and contraction wave velocity (CWV) of liquid, semisolid, and solid boluses. Ten healthy subjects underwent MII swallow evaluation with various boluses of sterile water (pH 5), applesauce, three different sized marshmallows, and iced and 130 degrees F water. The effect of bethanechol was also studied. There was no difference in BTT or CWV for all water volumes from 1 to 20 ml. There was significant linear increase of BTT with progressively larger volumes of applesauce, and BTT of applesauce was longer than for water. BTT was significantly longer with large marshmallows vs. small and medium and was longer than for water. BTT for iced water was similar to 130 degrees F water. Applesauce showed a significant linear decrease of CWV with progressively larger volumes and was slower than water. Marshmallow showed significantly slower CWV with the large vs. small, and CWV for ice water was significantly slower than 130 degrees F water. Therefore, BTT of liquid is constant, whereas BTT of semisolid and solid are volume dependent and longer than liquids. CWV of semisolids and solids are slower than liquids. CWV of cold liquids is slower than warm liquids. MII can be used as a discriminating test of esophageal function.

Adult↗
PubMed2001

Medical therapy for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a chronic condition that ranges from mild, intermittent symptoms to more severe cases of esophageal strictures and possibly adenocarcinoma of the esophagus. The etiology of GERD is multifactorial, although transient lower esophageal sphincter relaxations are thought to play an important role in addition to poor esophageal clearance and weak lower esophageal sphincter pressures. Lifestyle modifications and over-the-counter medications may be used to treat GERD. After these methods are tried, therapy with histamine receptor type 2 antagonists is the best treatment, although increasingly, proton pump inhibitors are being used. Long-term therapy needs to be maintained in patients with GERD, in contrast to those patients with peptic ulcer disease. The role of lifestyle modifications is described, and the costs of the various regimens are compared.

Antacids↗
PubMed2001

Aggressive acid control: minimizing progression of Barrett's esophagus.

Barrett's esophagus (BE) is a change in the cellular structure of the lower esophagus believed by many to be caused by frequent acid exposure. The condition is troublesome because of a tendency toward cell proliferation, dysplastic transformation, and cancerous changes within the lesions. It is speculated that the pronounced increase in esophageal adenocarcinoma during the past 25 years may be attributable to acid reflux and associated BE. Strict acid control may cause lesion regression in these patients. However, pH monitoring to confirm adequate acid control is essential, and more than 1 drug may be needed to achieve adequate acid control and manage many patients. More research is needed to determine whether aggressive acid control reduces the dysplasia and cancer risk associated with BE.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Medical therapy of supraesophageal gastroesophageal reflux disease.

Medical therapy of supraesophageal gastroesophageal reflux disease (GERD) is based on the principals for treating patients with heartburn and erosive esophagitis, observations from the few available clinical trials, and clinical experience. In general, patients with supraesophageal GERD require higher doses of antireflux therapy, principally with proton pump inhibitors, for longer periods of time to effectively relieve symptoms compared with patients with heartburn and/or erosive esophagitis. This article reviews the current literature and discusses a suggested approach to medical management of these often complex patients.

Algorithms↗