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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 55 records · Page 3Linked to original sources
PubMed2000

Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole.

BACKGROUND: In patients with severe gastro-oesophageal reflux disease (GERD), proton pump inhibitors are being used increasingly in twice-daily regimens to improve control of gastric acidity. Few data exist to compare the ability of the most-often used proton pump inhibitors, omeprazole and lansoprazole, to control gastric acid at twice-daily dosage regimens. Nocturnal acid breakthrough, defined as gastric pH < 4.0 continuously for > 60 min, may compromise treatment goals in patients with GERD. AIM: To compare the effects of omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. on gastric acidity and the relative ability of each dosage regimen to prevent acid breakthrough. METHODS: In a crossover pharmacodynamic study, 20 healthy volunteers (10 male, 10 female, mean age 38 years) were given omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. for 7 days each, in a randomized manner. Each dosage regimen was separated by a minimum 7-day period where no medication was administered. On day 7 of each regimen, 24-h intragastric pH-metry was performed. The percentage of time for which gastric pH was below 4.0 and 3.0, the occurrence of daytime and nocturnal acid breakthrough, and the duration of action of each regimen were compared. Non-parametric statistics for paired data were used. RESULTS: The percentage time for which gastric pH was below 4.0 was significantly lower with omeprazole 20 mg b.d. (median 14.8%) than with lansoprazole 30 mg b. d. (median 24.2; P=0.0372). Fourteen subjects showed more effective acid control when taking omeprazole; these were significantly more often H. pylori-negative patients compared with those for whom acid control was better on lansoprazole (P < 0.001). Nocturnal acid breakthrough occurred in seven patients (35%) on omeprazole and in 10 (50%) on lansoprazole (N.S.). CONCLUSION: In healthy volunteers, twice-daily dosing of omeprazole 20 mg b.d. appears to be significantly more effective than lansoprazole 30 mg b.d. in controlling gastric acidity. The clinical importance of such a difference remains to be defined in GERD patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Proton pump inhibitors: better acid suppression when taken before a meal than without a meal.

BACKGROUND: Proton pump inhibitors including omeprazole and lansoprazole inhibit gastric acid secretion by selectively and non-competitively inactivating the H+, K+ ATPase molecules of the parietal cell, but possibly only those that are actively secreting acid. This might imply that stimulation of acid secretion by a meal is necessary for optimal inhibition of gastric secretion. AIM: To quantify and compare the effect on daytime gastric acidity of omeprazole 20 mg or lansoprazole 30 mg daily taken 15 min before breakfast, with that of the same drug taken without a meal. METHODS: Twenty-one healthy volunteers were randomized to receive either omeprazole or lansoprazole. They were given the drug for two separate periods of 7 days in randomized order and at least 7 days apart. During one period the study medication was taken before breakfast; during the other it was taken at the same hour, but with no meal until 12:00 hours. Lunch was standardized. On day 7, intragastric pH-metry was performed, starting at 08:00 hours. Tracings were analysed for the 8-h period from 08:00 hours until 16:00 hours with regard to percentage time for which gastric pH was below 4.0 and 3.0, and median gastric pH. Tracings were also analysed after removing the 1 h breakfast period, to exclude the buffering effect of the meal. RESULTS: When taking the drug with breakfast, the median percentage time for which gastric pH < 4.0 was 17.2 (interquartile range 4.6-45.5), compared with 42.0 (interquartile range 31.4-48.8) when taken without food (P=0.01). Fifteen subjects had better control of gastric acidity when the medication was taken with breakfast. A pH threshold of 3 and median pH showed similar differences. When the breakfast period was removed, the differences were no longer statistically significant. CONCLUSIONS: When therapy with omeprazole or lansoprazole is indicated, medication should be taken before a meal for optimal control of daytime gastric acidity.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease.

BACKGROUND: Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro-oesophageal reflux disease (GERD). METHODS: To investigate the potential clinical utility of tegaserod in GERD, a five-period crossover study (balanced Latin square) was designed to evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour manometry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2-week treatment period in 19 patients with mild-to-moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure. RESULTS: Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistically significant decreasing (P < 0.05) for the entire treatment group (percentage time for which pH < 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose=8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sphincter relaxations frequency decreased in the 1-2.5 h post-dose. CONCLUSIONS: Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.

Adult↗
PubMed2000

Peristaltic pressure profiles of the human esophagus.

Using a low-compliance pneumohydraulic infusion system, we mapped the entire esophagus of nine volunteers with no history of esophageal disease, centimeter by centimeter, to see if there was pressure symmetry throughout the esophagus during 5 mL wet swallows. We found that esophageal length varied from 21-25 cm. The esophageal low-pressure zone (LPZ) varies in distance from the upper esophageal sphincter (UES) (4-8 cm). The length of this LPZ is 2-3 cm in most subjects but low pressures (<50 mmHg) may occur for longer intervals in some. The amplitudes of most paired swallows were within 10 mmHg of each other, and in only 10% of swallows was the pressure difference more than 15 mmHg. We conclude that there is radial pressure symmetry throughout the normal esophagus. The LPZ coincides closely to the 50-50 point where the percentage of striated and smooth muscle distribution in the circular and longitudinal muscles is equal.

Adult↗
PubMed2000

Prior sensitization of esophageal mucosa by acid reflux predisposes to reflux-induced chest pain.

Esophageal acid exposure is believed to be a major source of unexplained chest pain; but, individual episodes of reflux in pH study are not consistently associated with chest pain. Our aim was to discover whether prior sensitization of esophageal mucosa by acid reflux predisposes to reflux-induced chest pain. Ambulatory pH studies of patients referred to our laboratory from January 1991 to November 1996 with noncardiac chest pain was reviewed. We compared the frequency of esophageal acid exposure in the 30 minutes preceding chest pain episodes with a positive symptom/reflux association (+SRA) to reflux with the frequency of acid exposure in the 30 minutes preceding those chest pain episodes that were not associated with reflux negative symptom/reflux association (-SRA). We analyzed the time esophageal pH <4, symptom index (SI) defined as percentage of chest pain episodes associated with reflux in the preceding 5 minutes, and amount of reflux in the 30 minutes preceding each chest pain episode. Of 104 patients, 52 had chest pain during their pH study, 10 had high SI (> or =50%), and 42 had low SI (<50%). Those with a high SI were significantly more likely to have an abnormal pH study (p = 0.015). Chest pain associated with reflux in proceeding 5 minutes (+SRA) was strongly associated (p < 0.002) with additional reflux episodes in the preceding 25-minute period. Chest pain related to reflux is associated with sensitization of the esophageal mucosa by prior reflux events.

Adult↗
PubMed2000

Effect of different recumbent positions on postprandial gastroesophageal reflux in normal subjects.

OBJECTIVE: Gastroesophageal reflux (GER) is increased in the right compared to the left recumbent position. Esophageal acid exposure is related to the acidity at the cardia, but the effect of body position on the acidity at the cardia has not yet been investigated. We aimed to investigate the mechanisms underlying increased esophageal acid exposure in the right recumbent position. METHODS: On 2 separate days a 4-h combined esophageal and lower esophageal sphincter (LES) manometry and pH recording of esophagus, gastric cardia, and corpus was performed in the right and left recumbent position after a high fat meal in 10 healthy subjects. RESULTS: In the right recumbent position a prolonged esophageal acid exposure (7.0% vs 2.0%, p < 0.03), a higher incidence of reflux episodes (3.8 vs 0.9/h, p < 0.03), more transient LES relaxations (TLESRs) (6.5 vs 3.2/h, p < 0.03), and higher percentage TLESRs associated with reflux (57.0% vs 22.4% p < 0.03) was recorded than in the left supine position. Acidity at gastric cardia and corpus was not affected by body position. CONCLUSIONS: Increased esophageal acid exposure in the right recumbent position relative to the left recumbent position is the result of a higher incidence of GER episodes caused by an increased incidence of TLESRs and higher percentage of TLESRs associated with GER. Body position does not affect the acidity at the gastric cardia and corpus.

Adult↗
PubMed2000

Total acid suppression and its effect on Barrett's esophagus.

Barrett's esophagus is a complication of gastroesophageal reflux disease (GERD) and may result from prolonged acid exposure in the esophagus. As a result, clinicians are investigating a possible relationship between acid suppression and a decrease in the risk of Barrett's esophagus progression. Some studies suggest that the length of Barrett's esophagus may be reduced with total acid suppression therapy. Other studies indicate that patients with Barrett's esophagus are less sensitive to acid-induced symptoms (e.g., heartburn). While these patients may feel better symptomatically, the acid may not be sufficiently reduced to prohibit further damage. Acid suppression, even on high-dose pharmacotherapy, does not always eliminate the nocturnal acid breakthroughs. The contrasting study results on this issue are discussed.

Antacids↗
PubMed1999

A practical approach to heartburn.

Heartburn and other symptoms of gastroesophageal reflux disease can be a lifelong problem, affecting millions of Americans each year. Fortunately, treatment has improved dramatically over the past decade. Medications currently available are remarkably safe and, with proper selection, almost universally effective. When indicated, surgical treatment is also highly effective.

Anti-Ulcer Agents↗
PubMed1999

Gastroenterology: a career for a lifetime.

Following is an edited reprint of the Presidential Address delivered by Donald O. Castell, M.D., during the AGA Plenary Session at Digestive Disease Week 1999.

Gastroenterology↗
PubMed1999

Medical therapy. Management of the refractory patient.

Although relatively rare, GERD patients refractory to medical therapy remain a challenge for the clinician. Refractoriness can be diagnosed only if the patient is properly studied on medication and if what should be adequate medical therapy has been given a sufficient therapeutic trial. Use of 24-hour intragastric and intraesophageal pH-metry has improved the ability to manage patients who appear to be nonresponders. Simple advice and minor adjustments to medical therapy are usually all that is needed for most patients, but in some, management requires knowledge of the principles outlined in this article. If followed, only a small group of patients should be medically refractory.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Prospective randomized comparison of pneumatic dilatation technique in patients with idiopathic achalasia.

We performed a randomized prospective study of pneumatic dilatation comparing a 30-mm and 35-mm Microvasive balloon dilator inflated for either 15 or 60 sec in patients diagnosed with idiopathic achalasia who were previously untreated. Twenty-four patients, 11 men, 13 women, mean age 45, range 18-81 years), were prospectively randomized for dilatation. History and physical examination, esophageal manometry, and barium swallow were performed before dilatation. Symptom self scores were assessed before dilatation, and one month and six months after dilatation. Pneumatic dilatation was successfully completed in all 24 patients, with one patient experiencing a confined perforation. Conservative treatment was employed, and the patient recovered fully. Two patients experienced a recurrence of symptoms and required a second dilatation. Evaluation of posttreatment symptom self scores indicates no difference between the 30-mm and 35-mm Microvasive balloon or inflation durations of either 15 or 60 sec. These data indicate that the more conservative 30-mm dilator inflated for just 15 sec delivers a symptom response equal to a more aggressive approach with the larger dilator inflated over longer duration.

Adolescent↗
PubMed1999

Effect of cyclic hormonal changes during normal menstrual cycle on esophageal motility.

Pregnancy has an inhibitory effect on motility of the gastrointestinal tract most likely related to increased levels of circulating female sex hormones. Similar fluctuations of hormones occur during the normal menstrual cycle, but to a much lesser degree. We studied the effect of these sequential hormonal changes on esophageal motility and acid exposure by performing an ambulatory esophageal motility/pH study (AEM/pH) during the follicular (days 2-4) and luteal phases [days 4-8 after the luteinizing hormone (LH) surge] of the menstrual cycle. Ten normal menstruating women aged 21-39 years, (mean age 31) were studied with a Konigsberg catheter positioned such that the pH probe was 5 cm above and pressure transducers 7 and 15 cm above the LES. Ovulation was predicted by LH detection kit, and serum progesterone levels were obtained in the luteal phase. Each study was performed for 16 hr and included meal, upright, and supine periods. Peristaltic contractions increased during the meal periods and decreased during supine periods. Simultaneous and isolated contractions increased during supine periods and decreased with meals. Number and amplitude of distal esophageal contractions did not differ significantly between follicular and luteal phase during meal, upright and supine periods. Median percentage of time of distal esophageal pH<4 and median acid clearance were similar between the two phases. In conclusion, esophageal motility and acid exposure, as measured by AEM/pH, are not affected by the hormonal changes that occur during the menstrual cycle.

Adult↗