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Biomedical subjects

D O Castell

Publications and source records attributed to D O Castell.

At least 343 records · Page 19Linked to original sources

Cimetidine and hematologic suppression: things are not always as they appear.

A 67-year-old man with a bleeding ulcer developed fever, thrombocytopenia, and neutropenia with eosinophilia coincidental to receiving 3600 mg of cimetidine. Failure to reduplicate the hematologic suppression after cimetidine rechallenge suggests the drug was not responsible for the change in circulating cells. Our patient is similar to the earlier reported cases of cimetidine-associated hematologic suppression. The role of cimetidine in these cases is impossible to determine because of the multifactorial possibilities for bone-marrow suppression. Recently, a fatal case of agranulocytosis associated with cimetidine has been reported. The possible mechanisms of granulocytopenia are reviewed, and it is suggested cimetidine may cause bone-marrow suppression by an idiosyncratic reaction. We believe the possibility of fatal aplastic anemia secondary to cimetidine is very rare and does not preclude a drug rechallenge when the benefit-risk ration warrants.

Aged↗

Current concepts of esophageal function.

Current state of the art methods for esophageal manometry may be performed with either a nonperfused probe with intraluminal transducers or a perfused catheter system. The perfusate should be driven by a low compliance pump through catheters 0.8 mm. in diameter. The upper esophageal sphincter pressure profile is asymmetrical, with higher pressures in the anterior and posterior directions than laterally. The lower esophageal sphincter pressures are higher in the left and left posterior directions. There is symmetry of peristaltic pressures in the body of the esophagus. The discussion of the physiology of swallowing includes the "on" response and the "off" and "duration" response. The lower esophageal sphincter is normally in a state of constant contraction and is relaxed following stimulation of the vagus nerve. The mechanisms of the control of the lower esophageal sphincter remain to be fully demonstrated.

Catheterization↗

Effect of prostacyclin on gastric emptying and secretion in rhesus monkeys.

The effects of prostacyclin (PGI2) on gastric emptying and secretion were studied in five unanesthetized chair-adapted rhesus monkeys. A dye dilution technique was used to determine simultaneously gastric fractional emptying, hydrogen ion (H+) output, fluid output, and H+ concentration of the gastric juice. A continuous intravenous infusion of either sodium carbonate buffer (control) or PGI2 (125, 175, or 250 ng/kg/min) was given during a 40-min basal period and following the intragastric administration of an 80-ml water load. During the basal period, 175 and 250 ng/kg/min significantly decreased H+ output compared to control. Only 250 ng/kg/min, however, significantly reduced basal fluid output compared to control. As a result, the H+ concentration of the gastric juice was lowered by both 175 and 250 ng/kg/min. The effects of PGI2 on H+ output, fluid output, and H+ concentration of the secreted juice after the water load were similar to those observed during the basal period. In addition to its anti-secretory action, PGI2 inhibited significantly postload, but not basal, gastric fractional emptying. Because a fall in intragastric H+ concentration is known to enhance fractional emptying, it appears that the retarding effect of PGI2 on fractional emptying is not mediated by its ability to suppress H+ output.

Animals↗

Esophageal dysfunction in esophagopharyngeal regurgitation.

Esophageal manometry was performed in 20 patients with esophagopharyngeal regurgitation, in 20 patients with severe chronic heartburn but without regurgitation, and in 20 normal subjects. The purpose of the procedure was to identify possible differences between these groups in upper esophageal sphincter and lower esophageal sphincter resting pressures, and in amplitude of peristaltic contraction in the distal esophagus. The mean peak upper esophageal sphincter pressures in normal subjects and in patients with chronic heartburn were significantly greater than in the patients with esophagopharyngeal regurgitation (101 and 108 vs. 54 mmHg, respectively). In the normal subjects, the mean lower esophageal sphincter resting pressure (19 mmHg) was significantly greater than for the heartburn group (14 mmHg) and for the patients with esophagopharyngeal regurgitation (10 mmHg). The amplitude of peristalsis was significantly lower in the group with regurgitation than in both normal subjects and the group with chronic heartburn. Nine normal subjects responded to intraesophageal infusion of 0.9% NaCl and 0.1 N HCl with a significant increase in upper esophageal sphincter resting pressure, but the group with esophagopharyngeal regurgitation showed no significant change. Patients with esophagopharyngeal regurgitation have lower esophageal sphincter hypotension, diminished peristaltic amplitude, upper esophageal sphincter hypotension, and diminished upper esophageal sphincter response to intraesophageal fluid. We conclude there is in these patients a breakdown of several normal esophageal mechanisms which ordinarily serve as barriers to esophagopharyngeal regurgitation.

Adult↗

Effects of vasoactive intestinal polypeptide (VIP) on lower esophageal sphincter in awake baboons: comparison with glucagon and secretin.

The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.

Animals↗

Pulmonary aspiration as a consequence of gastroesophageal reflux: a diagnostic approach.

A radioisotope scintiscanning technique that can document pulmonary aspiration of gastric contents in patients with gastroesophageal reflux is described. Six patients with suspected nocturnal aspiration from reflux were studied. Three of the six had positive lung scans 8 hr after intragastric placement of 10 mCi of technetium 99m sulfur colloid. Overnight intraesophageal pH monitoring revealed prolonged episodes of GE reflux in those with positive scans. These preliminary observations suggest that this scintigraphic technique may be an effective method for documenting pulmonary symptoms as a consequence of gastroesophageal reflux.

Adult↗

Somatostatin effects on lower esophageal sphincter function.

The effect of somatostatin (GH-RIH) infusion (2 microgram/min) on lower esophageal sphincter pressure (LESP) responses to various stimuli was evaluated in adult male baboons. GH-RIH infusion did not affect basal LESP, but did cause a significant suppression of mean immunoreactive insulin (IRI) to 5.8% of basal values (P less than 0.05). Pentagastrin IV caused dose-related increases in LESP that were unaffected by GH-RIH. Abdominal compression caused a threefold rise in LESP (P less than 0.005) both without and with GH-RIH. However, atropine (20 microgram/kg iv bolus) completely blocked this cholinergic LES pressure response. Intragastric alkali as well as intragastric glycine caused significant increases in LESP (P less than 0.05). These LESP responses to alkali and to glycine were totally abolished by GH-RIH. In conclusion, GH-RIH infusion in the baboon does not affect basal LESP, LES smooth muscle response to exogenous stimulation, nor a cholinergically mediated LES response. GH-RIH does inhibit the response of LESP both to intragastric alkali and to glycine by the apparent suppression of a hormonally mediated mechanism.

Alkalies↗

Altered gastric emptying and secretion in primary anorexia nervosa.

Primary anorexia nervosa (PAN) is an important psychiatric disease with a 7--21% mortality rate. Although altered gastrointestinal function may be an important aspect of its pathophysiology, no information is available concerning gastric emptying and secretion in those patients. During fasting, fractional emptying rates and hydrogen ion (H+) output were decreased twofold in PAN, as compared with healthy controls, and fluid output was slightly but not significantly decreased. Pentagastrin-induced peak stimulation of H+ output in PAN was 64% of that found in controls (P less than 0.05). Peak gastric fluid output was also significantly less in PAN patients, but suppression of fractional emptying produced by pentagastrin was of the same magnitude in both groups. Following a 250-ml water load, the magnitude and the duration of both the emptying and secretory responses were less in PAN patients than in controls. As a result, the initial increase of intragastric volume was greater in PAN patients than in controls, and the gradual return to fasting volume was delayed in those patients. Follow weight gain, fractional emptying tended to return toward control values, but was still significantly less than in controls following the water load. Gastric H+ and fluid output were not significantly modified following weight gain.

Adult↗