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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 235 records · Page 13Linked to original sources

Diffuse esophageal spasm: radiographic and manometric correlation.

Diffuse esophageal spasm (DES) is characterized by substernal chest pain, dysphagia, and a manometric pattern of frequent simultaneous contractions with intermittently normal peristalsis. The authors correlated the radiographic and manometric findings in 17 patients with DES to better clarify the role of radiography in the evaluation of this uncommon motility disorder. Incomplete or absent primary peristalsis was observed on radiographs in 13 patients (76%), and mild to severe tertiary activity was seen in 12 patients (71%). The mean estimated thickness of the esophageal wall in patients with DES was 2.6 mm compared with 2.5 mm in an age-matched control group of 17 patients with normal esophageal manometric findings (P greater than .05). The authors conclude that most patients with DES show abnormal esophageal motility on radiographs, although the findings were nonspecific and required clinical and manometric correlation. Esophageal wall thickness was normal in patients with DES and appears to be an overemphasized sign in differentiating DES from other esophageal motility disorders.

Adult↗

Chronic hoarseness secondary to gastroesophageal reflux disease: documentation with 24-h ambulatory pH monitoring.

Gastroesophageal reflux (GER) has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. To study this relationship, we used 24-h ambulatory intraesophageal or dual pharyngoesophageal pH monitoring in 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. Twenty-six of the patients (78.8%) had pH evidence of severe GER, being at least three times greater than the upper limit of normal. In contrast to 19 patients with proven esophagitis, this GER was worse in the upright position. Of 15 patients with both pharyngeal and esophageal probes, three had esophagopharyngeal reflux, and two had atypical unexplained pharyngeal decreases in pH to below 4.0. Less than half of the 33 patients had the typical symptoms of GER, and standard esophageal tests usually yielded normal findings. Occult GER, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness, who have laryngeal lesions suggestive of GER. The causative mechanisms are not clear. The 24-h esophageal pH monitor is useful in screening this potentially treatable problem.

Adult↗

A comparison of high and low fat meals on postprandial esophageal acid exposure.

Fatty foods have been identified as precipitating factors in symptomatic gastroesophageal reflux (GER). A fat meal has also been found to decrease lower esophageal sphincter pressure (LESP) in normal subjects. We used the ambulatory 24-h pH monitor to assess esophageal acid exposure in 10 normal subjects and 10 GER patients following low and high fat meals eaten in two body positions. The meals had nearly identical protein content, volumes, and calories. On successive days, patients ingested one of the meals twice, followed by random assignment to 3 h upright and 3 h recumbent position. Acid exposure for each hour over a 3-h postprandial (PP) period was assessed as the percent time pH less than 4.0. Increased upright acid exposure occurred in normals after the high fat (6.2 +/- 2.1%; mean +/- SE) compared with the low fat meal (1.5 +/- 0.5%; p less than 0.05). GER patients had greater (p less than 0.05) acid exposure than normals in all study periods, but no differences were found between low and high fat meals in either study position. High fat meals induce upright GER in normals, but do not significantly affect the abnormal amount of GER in patients. In addition, progressive increases in acid exposure were found over the 3 postprandial hours in GER patients in a recumbent position. The findings are consistent with prior data showing decreased LESP with a fat meal in normals.

Adult↗

Acid-induced esophagitis in cats is prevented by sucralfate but not synthetic prostaglandin E.

The cytoprotective effects of liquid sucralfate and a synthetic analog of prostaglandin E1 (PGE1) on acid-induced esophagitis in cats were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N HCl at 1 ml/min for 20 min. Animals were infused for either one or three days. Mucosal lesions were evaluated by blinded investigators using both fiberoptic endoscopy and light microscopy. Histologic changes included basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions in both one- and three-day infusions, demonstrated by both endoscopy and quantitative histologic scoring. Indomethacin (200 micrograms/kg) given prior to sucralfate and acid did not affect sucralfate cytoprotection. Synthetic PGE1, given in doses of 5 micrograms/kg and 100 micrograms/kg, afforded no esophageal cytoprotection. These studies indicate that sucralfate is cytoprotective against acid-induced esophageal injury in cats, an effect that does not appear to be mediated by prostaglandin. In addition, synthetic PGE1 does not confer protection in this animal model.

Animals↗

Ambulatory 24-hour esophageal pH monitoring. Reproducibility and variability of pH parameters.

If 24-hour esophageal pH monitoring is to be a useful diagnostic tool, it must reliably discriminate gastroesophageal reflux patients despite daily variations in distal esophageal acid exposure. To address this issue, we studied 53 subjects (14 healthy normals, 14 esophagitis patients, and 25 patients with atypical symptoms) with two ambulatory pH tests performed within 10 days of each other. Intrasubject reproducibility of 12 pH parameters to discriminate the presence of abnormal acid reflux was determined. As a group, the parameters of percent time with pH less than 4 (total, upright, recumbent) were most reproducible (80%). Therefore, a subject was defined as having gastroesophageal reflux disease if at least one of these three values were abnormal. Intrasubject reproducibility for the diagnosis of reflux disease was 89% for the entire sample. Among subsets, the reproducibility was 93% for the normals and esophagitis patients and 84% for the atypical symptom patients. Total percent time with pH less than 4 was the single most discriminate pH parameter (85%) and nearly equaled that of the three combined parameters (89%). The intrasubject variability of this parameter was determined by the mean +/- 2 SD of the relative differences between the two test results for all 53 subjects. Total percent time with pH less than 4 may vary between tests by a factor of 3.2-fold or less (218% higher to 69% lower). We conclude: (1) ambulatory 24-hr esophageal monitoring is a reproducible test for the diagnosis of gastroesophageal reflux disease; and (2) the large intrastudy variability in 24-hr total acid exposure may limit this test's usefulness as a measurement of therapeutic improvement.

Adult↗

Esophageal motility disorders.

Esophageal motility disorders consist of a complex array of disturbances in normal esophageal function associated with dysphagia, gastroesophageal reflux, and noncardiac chest pain. A thorough knowledge of normal esophageal anatomy and physiology is important to a full understanding of these motility derangements. Through a complicated interaction of neuromuscular and hormonal influences, the voluntary act of swallowing transforms into an automated sequence of peristaltic waves propelling food and liquids into the stomach in concert with coordinated relaxation of the sphincters. Anatomic and physiologic barriers exist within the esophagus protecting against gastroesophageal reflux and aspiration. With improvements in diagnostic tools such as barium contrast radiography, scintigraphy, pH measurements, and esophageal manometrics with provocative testing, motility disorders have become better defined and understood. Primary motility disorders consist of achalasia, diffuse esophageal spasm (DES), "nutcracker esophagus," hypertensive lower esophageal sphincter, and nonspecific esophageal motility dysfunction (NEMD). A host of secondary and miscellaneous motility disorders also affect the esophagus, including scleroderma and other connective tissue diseases, diabetes mellitus, Chagas' disease, chronic idiopathic intestinal pseudo-obstruction, and neuromuscular disorders of striated muscle. Gastroesophageal reflux disease (GERD) may also be promoted by associated motility disturbances. Treatment modalities include surgical myotomy; dilatation; and pharmacologic manipulations, including use of nitrates, calcium-channel blockers, H2-blockers, and psychotropic drugs where appropriate.

Deglutition↗

Chest pain associated with esophageal disease.

When a patient presents with anginalike chest pain, the first objective is to rule out heart disease. Once cardiac problems have been ruled out, the second objective is to determine whether the history and/or symptoms suggest an esophageal abnormality. The diagnosis of gastroesophageal reflux-associated chest pain can occasionally be made from barium radiographic or endoscopic findings. A series of additional esophageal tests--motility studies, Bernstein test, edrophonium test, and balloon distention test--may be performed to help ascertain whether the pain stems from the esophagus. Reassurance should precede specific drug therapy. If any of the test results suggest gastroesophageal reflux, a trial of therapy for this indication, eg, a histamine2 receptor blocker, should be initiated. An esophageal motility disorder may be treated with an anticholinergic agent, nitro-glycerinlike product, or mild tranquilizer. If necessary, use of a calcium channel blocker may be appropriate.

Angina Pectoris↗

Histamine H2 receptor stimulation increases gastric emptying in monkeys.

We studied the effect of the specific H2 receptor agonist dimaprit on gastric emptying using a dye dilution technique in five chair-adapted rhesus monkeys to determine simultaneously gastric emptying and H+ secretion. Continuous subcutaneous injections of either saline alone or dimaprit (15, 30, 60, 120, and 240 nmol.kg-1.min-1) were given in random order on separate days. Both fractional emptying rate and H+ output were significantly increased by higher doses of dimaprit, with resulting twofold concurrent increase of intragastric H+ concentration. Because intragastric administration of H+ decreases gastric emptying and secretion, we evaluated the possibility that the stimulatory action of a histamine H2 agonist was underestimated when gastric pH was greater during control than after dimaprit. When exogenous HCl was added to the stomach to achieve H+ concentrations similar to those measured after dimaprit, both fractional emptying and H+ secretion were decreased twofold. When these "acidified control values" were used as a point of comparison, the stimulatory effect of dimaprit on both fractional emptying and gastric secretion was greater, suggesting that the stimulatory actions of dimaprit are underestimated if one does not take into account the differences in intragastric H+ concentrations.

Animals↗

On-line computer analysis of human lower esophageal sphincter relaxation.

Lower esophageal sphincter (LES) relaxation is usually interpreted by a subjective, mostly qualitative analysis. We studied sphincter relaxation in humans using a computer program for on-line analysis that provides objective measures of gastric pressure, resting LES pressure, percent of relaxation, residual pressure during relaxation, duration of relaxation, and area of relaxation. The program was validated by comparing computer-analyzed values to mean values obtained from manual readings by five individuals. Excellent correlation was obtained for all standard parameters. The parameters of LES relaxation for both wet and dry swallows were similar using either a carefully placed single recording orifice or a Dent sleeve. The one exception was the duration of LES relaxation, which was significantly shorter with the sleeve. All relaxation parameters and peristaltic velocity were then studied in 10 volunteers during 5 dry and 5 wet swallows under base-line conditions and after both atropine (10 micrograms/kg iv) and bethanechol (40 micrograms/kg sc). These studies showed that LES relaxation is affected by type of swallow (dry vs. wet). Percent of relaxation may not be the best measure of relaxation because it is too dependent on resting pressure. Residual pressure is not dependent on base-line pressure and may better define relaxation. Duration of the relaxation is dependent on the velocity of the peristaltic wave.

Adult↗

Respiratory complications of gastroesophageal reflux.

Gastroesophageal reflux may predispose patients to pulmonary complications such as bronchospasm and aspiration pneumonitis. This is especially true in patients who are critically ill, those with reflux-induced asthma and those undergoing general anesthesia. Decreasing the amount of acid reflux reduces the potential for respiratory complications. In patients at risk, administration of H2-receptor antagonists minimizes the risk of acid aspiration and resolves asthma symptoms.

Gastroesophageal Reflux↗

The symptom index: a clinically important parameter of ambulatory 24-hour esophageal pH monitoring.

Ambulatory 24-h esophageal pH monitoring is an accurate quantitative test of gastroesophageal reflux (GER). However, it does not answer the question: are the patients' symptoms due to GER? We developed a numerical scale to quantify the percent association between symptoms and pH less than 4--the symptom index (SI). In 100 consecutive patients with heartburn or chest pain, the SI for the chief complaint was either high (greater than 75%) or low (less than 25%) in 77% of cases. A similar bimodal distribution was seen when heartburn or chest pain symptoms were individually evaluated. There was a good association between high SI and the presence of GER (97.5%), as well as low SI and a normal 24-h pH study (81.1%). Endoscopy was normal in 89.5% of patients with low SI, but patients with high SI had esophagitis in only 69.7% of cases. The Bernstein test showed a poor association with the SI. Therefore, the SI gives clinically relevant information regarding the role of acid reflux and patient's symptoms. We believe this simple calculated index should be included in the analysis of 24-h esophageal pH studies.

Chest Pain↗

The changing faces of the nutcracker esophagus.

Although the nutcracker esophagus, characterized by high amplitude peristaltic contractions with mean distal amplitude greater than 180 mm Hg, is the most common esophageal motility disorder associated with noncardiac chest pain, little is known about its natural history. Therefore, we reviewed the manometric tracings of 23 patients with the nutcracker esophagus who had an average of 4.6 studies during a mean period of 32 months. Ten age-matched volunteers with normal baseline manometry who had undergone multiple studies (mean 5.8) over a mean time span of 32 months served as controls. In the 17 nutcracker patients with three or more motility studies, the variability of mean distal amplitudes between studies was 41.9% +/- 4.1 (+/- SE) compared to 27.0% +/- 3.3 for the control subjects (p less than 0.01). Highest distal pressures were noted during the first study in 11 of 17 patients (65%) compared to two of 10 controls (20%). The consistency of the diagnosis of nutcracker esophagus varied considerably: four patients always had high amplitude pressures, three patients only had the nutcracker diagnosis on the initial study, and 10 patients intermittently had pressures in the nutcracker range. Overall, these 17 patients had the diagnosis of the nutcracker esophagus confirmed on only 54% of subsequent studies. Changes in motility patterns were intermittently seen in six of 23 patients: one diffuse spasm and five nonspecific motility disorders. None of the control subjects developed high amplitude contractions or changed their motility pattern on serial testing. The possible pathophysiological implications of the changing faces of the nutcracker esophagus are discussed.

Chest Pain↗

Chocolate and heartburn: evidence of increased esophageal acid exposure after chocolate ingestion.

Chocolate has been shown to decrease mean basal lower esophageal sphincter (LES) pressure, providing a rationale for the pathogenesis of chocolate-induced reflux symptoms. We assessed the relationship between chocolate ingestion and increased esophageal acid exposure using intraesophageal pH monitoring. Compared with ingestion of a dextrose control solution of similar volume, osmolality, and calories, postprandial ingestion of chocolate resulted in a significant increase in acid exposure in the first postprandial hour in patients with esophagitis. We conclude that this finding supports recommendations that patients with reflux esophagitis abstain from chocolate.

Adult↗