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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 289 records · Page 16Linked to original sources
PubMed1985

Calcium-channel blocking agents for gastrointestinal disorders.

Calcium-channel blocking agents have a potential role in regulation of gastrointestinal tract function by decreasing smooth muscle contraction and possibly inhibiting cellular secretion. Most studies to date have concentrated on the ability of these drugs to inhibit smooth muscle contraction. Verapamil and diltiazem have been shown in animals (opossum, baboon) to produce decreased contractions in esophageal smooth muscle, resulting in a decreased amplitude of peristalsis and decreased lower esophageal sphincter pressures. In studies in man, oral doses of diltiazem and nifedipine have likewise been shown to have similar effects on the esophagus. At present, there is no experimental evidence of a major antisecretory effect of these drugs. In clinical trials, nifedipine has been shown to have a greater effect than placebo in improving symptoms in patients with achalasia, and diltiazem has been suggested as potential therapy in patients with chest pain secondary to excessive esophageal contraction. The precise role for calcium-channel blocking drugs in therapy of gastrointestinal disease is still being explored.

Animals↗
PubMed1985

Lidocaine inhibition of esophageal peristalsis and lower esophageal sphincter pressure in baboons.

Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function.

Animals↗
PubMed1985

Nifedipine: a potent inhibitor of contractions in the body of the human esophagus. Studies in healthy volunteers and patients with the nutcracker esophagus.

Nifedipine, a calcium channel blocker, inhibits lower esophageal sphincter pressure but has only minimal effect on esophageal contractions. We investigated the effects of nifedipine on esophageal contractions in 5 healthy volunteers and 10 patients with the nutcracker esophagus. Nifedipine (10, 20, 30 mg) or placebo was ingested as capsules in a double-blind design on 4 separate days. In volunteers, mean distal amplitude decreased 16.6%, 38.4%, and 49.0% as the nifedipine dose was increased. These changes were significantly (p less than 0.05) different from the placebo response and were sustained with higher doses. Patients with the nutcracker esophagus had a similar response, decreasing mean distal amplitude significantly (p less than 0.05) by 16.3%, 36.2%, and 54.2%. In both groups, nifedipine also had a significant (p less than 0.05) dose-dependent depressant effect on distal duration, although to a lesser degree than on amplitude. The percent decrease in distal amplitude showed good correlation (p less than 0.01) with plasma nifedipine concentrations at 60 min. These studies suggest nifedipine may be useful in the treatment of motility disorders of the esophageal body.

Adult↗
PubMed1985

Reflux esophagitis: an update.

In recent years, much has been learned about the pathogenesis, diagnosis, and treatment of gastroesophageal (GE) reflux disease. Mucosal resistance, gastric contents, esophageal acid clearance, gastric emptying, and incompetency of the lower esophageal sphincter are contributing factors to GE reflux. Use of the various diagnostic tests and an overview of current therapy are summarized.

Alginates↗
PubMed1985

Edrophonium: a useful provocative test for esophageal chest pain.

Esophageal motility disorders may be an important cause of noncardiac chest pain. To improve our diagnostic yield, we studied the use of edrophonium as a provocative test for inducing esophageal chest pain in 50 symptomatic patients without coronary artery disease and in 25 age-matched controls. Edrophonium (80 micrograms/kg of body weight, intravenous bolus) induced chest pain in 15 (30%) patients and in no controls. Edrophonium increased esophageal amplitude and repetitive contractions to a similar degree in all subjects, but the change in duration (101 +/- 13% [SE] was significantly greater (p less than 0.02) in patients in whom chest pain was induced. Drug specificity was assessed in 9 patients during cardiac catheterization, but no significant change was seen in coronary artery diameter, blood pressure, or heart rate. Further clinical testing using a placebo control confirmed a positivity rate of 28% in 125 unselected patients with chest pain referred to our laboratory; false-positive tests were infrequent (5.6%). No important side effects were seen. Edrophonium is useful for provoking esophageal chest pain.

Adult↗
PubMed1985

Respiratory complications of gastroesophageal reflux.

Gastroesophageal reflux (GER) and its many manifestations are extremely common problems. The pulmonary manifestations are the least well understood and are often unrecognized. We reviewed the available literature on the subject of respiratory tract symptoms secondary to chronic GER in an attempt to promote wider recognition of this relationship. We hope that this review will call attention to the potential importance of GER in those patients in whom such a mechanism might be responsible for pulmonary symptoms.

Adrenergic beta-Agonists↗
PubMed1985

Diagnosis of noncardiac chest pain in older patients.

Barium swallow and gallbladder study may reveal esophageal or gastric cancer, esophageal or duodenal ulcer, or gallstones. If serious GI tract disorders such as these are ruled out, the next step is to seek an esophageal source of recurring chest pain. Intraesophageal acid infusion and edrophonium chloride (Tensilon) stimulation can be used in the office to reproduce chest pain secondary to an esophageal disorder. With either test, reproduction of the patient's typical chest pain is positive. About one-third of patients seen in our laboratory with noncardiac chest pain have a positive response.

Aged↗
PubMed1984

Esophageal bougienage in symptomatic patients with the nutcracker esophagus. A primary esophageal motility disorder.

A wide variety of therapies have been suggested for patients with painful esophageal motility disorders. In a prospective, double-blind, cross-over clinical trial, we evaluated the effectiveness of mercury bougienage ("placebo," 24 F; "therapeutic," 54 F) in eight symptomatic patients with the nutcracker esophagus (NE). There were no significant differences between the placebo or therapeutic dilators in relation to chest pain, dysphagia, lower esophageal sphincter pressure, or amplitude. Chest pain scores after completion of this trial were significantly lower than baseline scores, irrespective of the sequence of dilators used. No subjective or objective improvement could be demonstrated when "therapeutic bougienage" was compared with "placebo bougienage" in patients with the NE. The improvement in symptoms at the completion of the study may result from the close physician-patient interaction, suggesting that this may be more important than the actual size of the bougie.

Adult↗
PubMed1984

Histologic evaluation of chronic gastroesophageal reflux. An evaluation of biopsy methods and diagnostic criteria.

Controversy exists regarding the appropriate method for biopsy confirmation of esophageal reflux injury. We have compared endoscopic pinch biopsy (PB) with endoscopically directed Rubin tube suction biopsy (SB) in 40 patients with symptomatic gastroesophageal reflux disease (GERD). Utilizing a plastic tube attached alongside the endoscope, SB at specific sites in the esophagus can be easily obtained. Suction biopsy was rated superior to PB for adequacy of tissue, ability to make an interpretation, and certainty in diagnosis. These differences were most pronounced in patients with endoscopic grades 0 and 1 + esophagitis in which 59% of PBs were uninterpretable compared to 23% of SBs. The passage of the Rubin tube was easily done and could be performed repeatedly. Six of 40 patients (15%) developed substernal chest discomfort in the 24 hr following SB. We conclude that SB is the most appropriate way to evaluate histologic changes related to reflux injury and that this method is mandatory in symptomatic patients with minimal endoscopic evidence of esophagitis (0-1 +).

Adult↗
PubMed1984

Computer-Aided analysis of human esophageal peristalsis. I. Technical description and comparison with manual analysis.

Manual and computer analysis of esophageal peristaltic activity induced by swallows of 5ml water were compared in 6 healthy subjects under basal conditions and following i.v. injection of 4 pharmacological agents: edrophonium (E, 0.08mg/kg), atropine (A, 0.6mg), pentagastrin (PG, 0.6mcg/kg), and glucagon (GL, lmcg). Esophageal manometry was performed using a low compliance perfusion system and recorded on paper for standard manual analysis. The signal was concurrently taped on an analog recorder for subsequent digitization and analysis on a PDP-11 computer using a locally developed program. With both methods we determined the wave amplitude, duration, average upward slope (dP/dT), and velocity of wave progression. In addition, the computer allowed calculation of area under each wave and maximum upward slope (Max dP/dT). We found no significant difference between results of the parameters measured using both methods. Wave amplitude was significantly increased by E and significantly decreased by A. Average upward slope was decreased and velocity was significantly increased only by A. Computer-calculated wave area and Max dP/dT were significantly changed by both E and A. PG and GL had no effect on any of the measured parameters of the peristaltic wave. Esophageal peristalsis can be analyzed using a computer-aided method, providing a rapid and objective measurement of classical parameters and access to more in-depth analysis.

Adult↗
PubMed1984

Effects of oral calcium blocker, diltiazem, on esophageal contractions. Studies in volunteers and patients with nutcracker esophagus.

Animal studies have shown that calcium blocking drugs decrease lower esophageal sphincter pressure and inhibit peristaltic amplitude and duration. In a single-dose acute study, we compared the effects of a new oral calcium blocker, diltiazem (90, 120, 150 mg) with placebo in five volunteers and 10 patients with chest pain/dysphagia and high amplitude peristaltic contractions in the distal esophagus--nutcracker esophagus. In volunteers, diltiazem had no effect on esophageal contractions when compared to baseline values or placebo. In contrast, most doses of diltiazem significantly (less than 0.05) decreased amplitude and duration of peristaltic contractions in patients with nutcracker esophagus. Despite adequate blood levels, interstudy analysis was not statistically significant because placebo also decreased these parameters. During an eight-week open-labeled study, diltiazem 90 mg QID significantly (P less than 0.01) improved symptoms of chest pain and dysphagia. Side effects were minimal. Although oral diltiazem has minimal effect on baseline esophageal contractions, our chronic study suggests it may modify transient increases in neuromuscular tone associated with esophageal chest pain. These observations warrant further placebo-controlled studies.

Adult↗
PubMed1984

Oesophageal motility: recent advances and implications.

Oesophageal motility studies have greatly enhanced our knowledge of the physiology of the oesophagus. The abnormalities, particularly of the LOS, that occur in gastro-oesophageal reflux disease have been extensively studied. Although motility studies have relatively little impact on the clinical management of the majority of patients with oesophagitis, they are indicated when there is diagnostic doubt and most especially when surgical treatment is being considered. In numerical terms oesophageal motility studies are required most often for the investigation of obscure dysphagia or non-cardiac chest pain. Research is continuing to expand our knowledge of the oesophageal dysmotility syndromes.

Esophageal Diseases↗
PubMed1984

Esophageal radionuclide transit tests. Potential false-positive results.

Esophageal radionuclide transit testing is a sensitive technique for assessing esophageal clearance. Experience with the technique in 150 patients has led to an awareness of several pitfalls which might lead to false-positive results. Potential problems may be grouped into technical factors, clinical aspects, and misinterpretations. Examples of these are presented and techniques to minimize such problems are discussed.

Deglutition Disorders↗