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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 19 recordsLinked to original sources
PubMed1992

Chest pain of undetermined origin: overview of pathophysiology.

Patients with unexplained chest pain represent a major clinical dilemma for primary-care physicians, gastroenterologists, and cardiologists. References to this prevalent clinical problem date to more than 150 years ago; confusion about its pathophysiology has resulted in the use of a variety of descriptive terms such as "noncardiac," "atypical," and "angiographically negative" chest pain. Since none of these terms applies to all cases, the description "chest pain of undetermined origin" may be preferable. Because the esophagus has a similar location and innervation as the heart, an esophageal source for unexplained chest pain syndromes has been frequently suggested. Recent studies have emphasized the importance of gastroesophageal reflux as a likely component of esophageal pain. Moreover, "irritable esophagus" is an emerging concept that implies a generalized alteration in esophageal pain threshold, that is, abnormal nociception. The potential effects of stress or altered psychological states in this phenomenon must be considered, and the role of "panic attacks" in the production of pain in these patients needs to be clarified. In addition, stress may produce altered esophageal motility and lead to manometric abnormalities such as the "nutcracker esophagus" or a hypertensive lower esophageal sphincter. Finally, the precise contribution of the heart in producing pain in patients with normal coronary angiograms remains unclear because the precise role of microvascular angina has yet to be clarified.

Angina Pectoris↗
PubMed1992

Esophageal balloon distention and cerebral evoked potential recording in the evaluation of unexplained chest pain.

A minority of patients presenting with the common clinical challenge of unexplained chest pain can be diagnosed as having an esophageal etiology for their pain using conventional manometric and provocative (acid infusion and edrophonium) testing. Esophageal balloon distention may provide an important adjuvant to routine testing. Most pain from the esophagus is mediated by visceral sensory receptors located near the myenteric plexus; these receptors respond to movements of the organ wall in response to contractions or distention. Balloon distention can be used to simulate this wall movement. Early clinical studies have been expanded by recent investigations demonstrating a lowered pain threshold in response to balloon distention in patients with both unexplained chest pain and nonobstructive dysphagia. The physiologic basis for this increased sensitivity is not clear. Balloon distention has several effects on esophageal motility that may play a role in producing pain. The recording of cerebral evoked potentials is a technique newly developed to provide an objective measurement of the subjective sensation of pain. Electrical and mechanical stimulation of the esophagus has been shown to produce cerebral evoked potentials. Recent investigations of cerebral potentials evoked by balloon-induced esophageal stimulation have confirmed that this response depends on pain production, have clarified the appropriate stimulus parameters, and have localized the site of origin of the evoked potential to the balloon site. Balloon distention may prove to be an important addition to current esophageal provocative testing, although widespread applicability has been hampered by the lack of a commercially available standardized balloon. Recording evoked potentials produced by esophageal stimulation may provide additional clues in unraveling the mystery of unexplained chest pain.

Brain↗
PubMed1992

Continuous versus intermittent acid exposure in production of esophagitis in feline model.

Our morphometric feline model of acid-induced esophageal damage histologically resembles human reflux esophagitis. The histologic scoring system includes intensity and linear extent of basal cell hyperplasia, intraepithelial and subepithelial segmented leukocytes, and ulcers. Each of these four categories is scored from 0 to 4, for a potential total score of 16. Some reports have indicated that the long-duration acid exposure episodes during recumbent nighttime reflux are apt to be associated with greater injury than shorter episodes during daytime upright exposure. We tested the hypothesis that longer single exposures to acid would incite greater morphologic damage in the cat than would multiple, shorter acid exposures. To study the influence of continuous versus intermittent hydrochloric acid exposure, groups of six cats each were infused continuously (single infusion) for 15, 20, or 30 min, and compared with cats infused for 2-min acid infusion times. Our studies indicate that total acid exposure and mucosal damage are more likely to be greater after multiple episodes of the same total duration with adequate clearing (ie, awake upright reflux) than after single long episodes of acid exposure that are poorly cleared (ie, sleeping).

Analysis of Variance↗
PubMed1992

Prolonged intraesophageal pH monitoring with 16-hr overnight recording. Comparison with "24-hr" analysis.

UNLABELLED: From studies in 43 patients (17 male, 26 female, mean age 51 years), we compared the analysis of the routine complete "24-hr" ambulatory esophageal pH monitoring study to that of the 16-hr overnight interval (4:00 PM to 8:00 AM). The latter included a major meal with an upright postprandial period and a recumbent period. All patients were monitored for at least 20 hr (median = 22.6 hr). The percent distal esophageal pH less than 4.0 and number of reflux episodes were measured for the total, upright, and recumbent periods of both the 16-hr and "24-hr" monitoring times. Significant (P less than 0.001) positive correlations were found for all comparisons between the two monitoring periods including percent time of pH less than 4.0 (total: r = 0.98; upright: r = 0.96) and number of episodes (totals r = 0.97; upright: r = 0.93). Patients were separated into normal and abnormal refluxers based on results of "24-hr" monitoring (pH below 4.0 greater than 4.2% total time; greater than 6.0% upright; greater than 1.2% recumbent). Based on this, sensitivity and specificity for 16-hr monitoring were as follows: total study: 86% and 95%; upright: 80% and 91%; recumbent: 100% for both. CONCLUSIONS: (1) a 16-hr overnight pH monitoring period can provide a reliable representation of "24-hr" distal esophageal acid exposure, (2) this shorter monitoring may improve patient acceptability and compliance, and (3) the symptom index was changed in 26.3% of patients using the 16-hr evaluation.

Electrodes↗
PubMed1992

Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid.

This study tested the hypothesis that (alginic) acid may have a preferential effect on reflux in the upright position. We evaluated the effect of a compound containing alginic acid plus antacid (extra-strength Gaviscon) versus active control antacid with equal acid-neutralizing capacity on intraesophageal acid exposure following a high-fat meal (61% fat: sausage, egg, and biscuit). In random sequence, each of the 10 volunteers received either alginic acid-antacid or control antacid immediately following and 1, 2, and 3 hr after the meal. The sequence was repeated for both test drugs in the supine and upright positions with constant pH monitoring. Alginic acid-antacid significantly decreased postprandial reflux in the upright position compared to an equal amount of antacid. This effect did not occur in the supine position. These findings support the hypothesis that alginic acid is primarily effective in the upright position and the clinical observations of the effectiveness of alginic acid on daytime reflux symptoms.

Alginates↗
PubMed1992

Effects of nifedipine on esophageal tone and perception of esophageal distension.

The effects of nifedipine (20 mg orally) on esophageal body resting tone and perception of esophageal distension were compared with those of placebo in 10 healthy volunteers, using a double-blind crossover design. A 3-cm silicon balloon positioned 10 cm above the lower esophageal sphincter was inflated with 2-20 ml of air, in 2-ml increments. The subjects scored their chest sensations, while pressure in the balloon was continuously recorded. In each experiment three series of measurements were made, at baseline and 15 and 30 min after administration of nifedipine or placebo. Bench tests were run to determine pressure-to-volume relationships for each of the balloons used in the study. Thirty minutes after nifedipine ingestion, a significant decrease in systolic blood pressure (from 112.6 +/- 2.3 to 99.0 +/- 2.0 mm Hg) was observed. Amplitude and duration of esophageal peristaltic contractions were significantly decreased by nifedipine (from 128.1 +/- 16.7 to 98.7 +/- 10.6 mm Hg and from 3.9 +/- 0.3 to 3.3 +/- 0.2 sec, respectively). With balloon volumes of 8 ml and higher, balloon pressures were higher with the balloon in the esophagus than on the bench, the difference being determined by the compliance of the esophagus. This difference rose from 18.5 +/- 6.8 to 40.2 +/- 7.2 mm Hg (8-20 ml) with placebo and from 23.1 +/- 3.7 to 35.9 +/- 5.8 mm Hg with nifedipine. No significant differences between nifedipine and placebo were found. The esophageal sensation scores increased linearly with increasing balloon volume from 6 ml onwards. Nifedipine had no significant effect on the perception of esophageal balloon distension.

Adult↗
PubMed1992

Randomized, double-blind, placebo-controlled crossover trial of pirenzepine in patients with gastroesophageal reflux.

A muscarinic receptor subtype 1 (M1) antagonist, pirenzepine, recently has been shown to be relatively free of the usual anticholinergic side effects on esophageal smooth muscle and thus has been implicated for the treatment of gastroesophageal reflux disease (GERD). However, the effect of pirenzepine on GERD remains to be defined. Thirteen patients who demonstrated GERD in a baseline 24-hr ambulatory intraesophageal pH monitoring study were randomized in a double-blind crossover fashion to receive pirenzepine and placebo. An ambulatory 24-hr intraesophageal pH monitor was used to assess reduction in reflux (esophageal pH less than 4.0) with respect to position (upright vs supine), to total number of reflux episodes, and to episodes greater than 5 min. A significant effect for pirenzepine was seen for episodes greater than 5 min (t = 2.61, P = 0.023) and a trend towards significance was seen for total (upright and supine positions combined) percent time of reflux (t = 2.13, P = 0.055). Although not statistically significant, pirenzepine consistently showed greater reduction in all parameters of reflux tested. A greater reduction in percent time of reflux in supine vs upright positions (pirenzepine: 58.9% vs 21.4%; placebo: 43.6% vs 7.3%) may be clinically important in prevention of esophageal injury due to reflux in the recumbent position. Pirenzepine may provide a unique alternative for some GERD patients who may be refractory to other therapies of GERD.

Adult↗
PubMed1992

Acute esophageal hemorrhage from a vagal neurilemoma.

A man with known systemic neurofibromatosis developed an acute upper gastrointestinal hemorrhage while hospitalized after a neurosurgical procedure. Endoscopic evaluation showed a vascular lesion with an appearance consistent with a Dieulafoy-type lesion in the distal esophagus. Despite multiple endoscopic procedures with attempted coagulation of the bleeding lesion, the patient continued to have life-threatening hemorrhaging. At thoractomy, a tumor was found to arise from the vagus nerve at the site of bleeding. This tumor was resected and histologically determined to be a neurilemoma. Acute bleeding into the esophagus associated with this type of tumor has not been previously reported.

Cranial Nerve Neoplasms↗
PubMed1992

Cerebral potentials evoked by oesophageal distension in patients with non-cardiac chest pain.

Cerebral evoked potential recording was used to study the oesophagus-brain axis in 10 controls and 10 patients with non-cardiac chest pain with a manometric diagnosis of either nutcracker oesophagus or diffuse spasm and a positive edrophonium test. A series of 50 inflations (10/minute; inflation rate of 170 ml/second) of an intraoesophageal balloon (5 cm proximal to the lower oesophageal sphincter) was performed in each subject. Three different inflation volumes were used and were individually determined to cause no sensation, slight sensation, and definite sensation, respectively (volume ranges: 2-8 ml, 5-18 ml, and 8-22 ml). All signals were coded and their quality was scored on a scale from 0 (no recognisable pattern) to 5 (well defined potential of good quality) by four 'blinded' observers. The evoked potential quality scores and amplitude of the major peaks increased significantly (p less than 0.01) with increasing sensation, both in patients and in controls. In the patients, quality score and amplitude of all four peaks of the evoked potentials were lower (p less than 0.05) and latencies of two of the four peaks were longer (p less than 0.02) than in the controls. The volumes of air required to produce the various sensations were lower in the patients (p less than 0.01). When divided by the balloon volume, amplitude and quality of the evoked potential were no longer significantly different between the groups. These results suggest that the increased perception of oesophageal distension in patients with non-cardiac chest pain is caused by altered central processing rather than (functionally) abnormal receptors in the oesophageal wall.

Adult↗
PubMed1992

Transnasal US of the esophagus: preliminary morphologic and function studies.

High-frequency catheter-based ultrasound (US) transducers can be inserted into the esophagus transnasally to evaluate esophageal wall structures. Studies were performed in two sheep esophagus specimens in vitro, in 17 healthy human subjects, and in 16 patients with esophageal abnormalities (eight with achalasia, four with scleroderma, three with esophageal carcinoma, and one with esophagitis). In the sheep specimens, endoluminal US delineated seven layers of the esophageal wall; these results correlated closely with histologic findings. Real-time US of the normal esophageal wall was performed during resting and swallowing. Muscles at the lower esophageal sphincter (LES) were shown to be thicker than muscles in the body of the esophagus. Thickening of the muscular layers at the LES in achalasia, dilated blood vessels within the submucosa in esophagitis, and fibrotic changes within the muscular layers in scleroderma were demonstrated. Extramural structures adjacent to the esophagus were also seen. These preliminary results suggest that transnasal esophageal US may become an important diagnostic tool in evaluation of the esophagus.

Adult↗
PubMed1992

Abnormal upper esophageal sphincter function in achalasia.

We describe the results of pharyngeal and upper esophageal sphincter (UES) manometry, using new solid-state computerized technology in 19 patients with achalasia, compared with 14 healthy controls. The major manometric finding in achalasia is an increased residual pressure in the UES. Other differences seen in patients with achalasia include a reduction in the duration of UES relaxation with swallowing and a more rapid onset of pharyngeal contraction after UES relaxation. We review previous descriptions of suspected pharyngeal and UES abnormalities in achalasia and compare them to our own.

Adult↗
PubMed1992

Manometric aspects of Zenker's diverticulum.

Zenker's diverticulum is thought to result from disordered coordination between the pharynx and upper esophageal sphincter. Manometric studies of the upper esophagus have been helpful in testing the hypothesis of dysmotility in the formation and growth of a Zenker's diverticulum; however, the data have provided conflicting evidence. Manometric studies show that resting upper esophageal sphincter pressure is normal in some patients with Zenker's diverticulum and decreased in others. Abnormal premature relaxation and contraction of the upper esophageal sphincter seen in some patients with Zenker's diverticulum may be accompanied by pharnygeal contractions against a closed sphincter. This abnormality is thought by some investigators to be the cause of Zenker's diverticulum, but not by others who have found normal upper sphincter relaxation. Future manometric studies will very likely elucidate the pathogenesis of Zenker's diverticulum.

Esophageal Diseases↗
PubMed1991

Diffuse esophageal spasm. A rare motility disorder not characterized by high-amplitude contractions.

Diffuse esophageal spasm (DES) has frequently been described as a motility disorder characterized by simultaneous, high-amplitude contractions. We reviewed the results of esophageal manometry testing on a total of 1480 patients referred to our lab over 36 months. Lower esophageal sphincter (LES) pressure was determined by a mean of four station pull-through. Esophageal body motility was assessed following 10 wet swallows. In our lab a diagnosis of DES is made when greater than 10% but less than 100% of contractions are simultaneous. Manometric findings of DES were rare, with an overall prevalence of 4% (56/1480). Of the 56 patients with a manometric diagnosis of DES, high-amplitude (mean greater than or equal to 180 mm Hg) peristaltic contractions were found in only two (4%). No simultaneous contractions with amplitude greater than or equal to 180 mm Hg were seen. Pressures of simultaneous contractions were consistently lower than peristaltic contractions. A hypertensive LES pressure (greater than or equal to 45 mm Hg) was present in 5/56 DES patients (9%). Poor LES relaxation was found in 7/56 DES patients (13%). We conclude that DES is a rare manometric finding, regardless of the reason for referral, and that the occurrence of high-amplitude contractions in DES is equally rare.

Esophageal Spasm, Diffuse↗
PubMed1991

Rationale for high-dose H2-receptor blockade in the treatment of gastro-oesophageal reflux disease.

Chronic gastro-oesophageal reflux disease is a common clinical problem. The underlying pathophysiology is considered to be acid injury to the oesophageal mucosa secondary to reflux of gastric contents across an incompetent lower oesophageal sphincter. Evidence suggests that gastro-oesophageal reflux disease is primarily a motility disorder, possibly the combined effect of decreased lower oesophageal sphincter pressure, abnormal oesophageal peristalsis, and, perhaps, delayed gastric emptying. The rationale for the use of acid-suppressing drugs in chronic gastro-oesophageal reflux disease is based on control of the known destructive role of acid and pepsin. Recent evidence indicates, however, that standard doses of H2-receptor blockers are often inadequate to control gastric acid-induced injury in many patients with chronic reflux. Long-term maintenance therapy with standard doses of these drugs has proved unsuccessful in approximately 50% of patients. More recent studies show that greater symptom relief and improved healing can be achieved with the use of larger doses of H2-receptor antagonists. This has been shown particularly with ranitidine at a dosage of 300 mg four times daily.

Animals↗
PubMed1991

Rationale and efficacy of conservative therapy for gastroesophageal reflux disease.

Major recent advances in the diagnosis and understanding of gastroesophageal reflux disease have afforded the practicing clinician a number of therapeutic options to treat the increasingly recognized affected patient population. With highly effective acid-suppressive therapies available, simple life-style modifications, such as selective food and medicine avoidance, weight loss, smoking cessation, elevation of the head of the bed, and the judicious use of antacids and alginate, have been relegated to a minor, if any, role in the management of these patients. The validity of these recommendations, however, remains consistent with our current understanding of the pathogenesis of gastroesophageal reflux disease. Although few well-designed placebo-controlled trials have been conducted, a review of the medical literature indicates an appreciable efficacy of these interventions, which are founded on well-studied physiologic determinants of gastroesophageal reflux. Most patients with gastroesophageal reflux disease can be managed by reassurance and simple life-style adjustments alone. The therapy for those with chronic or relapsing disease should always include the adjunctive reinforcement of these simple, efficacious, and cost-effective measures.

Alcohol Drinking↗