Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Giant cell arteritis as a cardiovascular entity.

Giant cell arteritis (GCA) is a relatively infrequent disorder that is underdiagnosed and little appraised in the field of general cardiology. However, it is important to be familiar with the clinical picture of this disease, especially because of the risk of developing fatal aortic aneurysms. If the disease is suspected after a thorough history and clinical examination combined with laboratory investigation, the diagnosis can be confirmed with (18)F-2-deoxy-glucose positron emission tomographic (FDG-PET) imaging. Early recognition of giant cell arteritis followed by prompt treatment with glucocorticosteroids will decrease the risk of developing large-vessel complications. (Neth Heart J 2009;17:281-3.).

8R-lisuride is a potent stereospecific histamine H1-receptor partial agonist.

The human histamine H1 receptor (H1R) is an important, well characterized target for the development of antagonists to treat allergic conditions. Many neuropsychiatric drugs are known to potently antagonize the H1R, thereby producing some of their side effects. In contrast, the tolerability and potential therapeutic utility of H1R agonism is currently unclear. We have used a cell-based functional assay to evaluate known therapeutics and reference drugs for H1R agonist activity. Our initial functional screen identified three ergot-based compounds possessing heretofore-unknown H1R agonist activity. 8R-lisuride demonstrated potent agonist activity in various assays including receptor selection and amplification technology, inositol phosphate accumulation, and activation of nuclear factor-kappaB with pEC50 values of 8.1, 7.9, and 7.9, respectively, and with varying degrees of efficacy. Based on these assays, 8R-lisuride is the most potent stereospecific partial agonist for the human H1R yet reported. Investigation of the residues involved in histamine and lisuride binding, using H1R mutants and molecular modeling, have revealed that although these ligands are structurally different, the lisuride-binding pocket in the H1R closely corresponds to the histamine-binding pocket. The discovery of a potent stereospecific partial H1R agonist provides a valuable tool to further characterize this important therapeutic target in vitro.

Effect of subtotal colectomy on gastric emptying of a solid meal in slow-transit constipation.

BACKGROUND: Idiopathic slow-transit constipation is considered a panenteral disease in which patients may have delayed gastric emptying. The effects of total abdominal colectomy and ileorectal anastomosis on upper gut motility are unknown. The aim of this study was to evaluate gastric emptying in patients with idiopathic slow-transit constipation before and after subtotal colectomy. METHODS: Gastric emptying of a solid meal was studied by scintigraphic technique in 11 patients with idiopathic slow-transit constipation. The total colonic transit time was more than 72 hours in all patients studied, with delay in transit in all segments of the colon. The gastric emptying test was repeated 3 to 6 months after total abdominal colectomy and ileorectal anastomosis in ten of these patients. Before and after surgery, patients filled out a questionnaire to record upper gut symptoms. RESULTS: Solid gastric emptying was delayed (T1/2 > upper limit of normal) in 7 of 11 patients with idiopathic slow-transit constipation. Gastric emptying T1/2 was almost similar before and after surgery. Mean +/- standard deviation was 142 +/- 91 minutes before surgery and 146 +/- 67 minutes after surgery. Symptoms of vomiting and belching improved significantly after surgery. Symptoms of nausea, bloating, and pyrosis also decreased, but these changes failed to reach statistical significance. CONCLUSION: Despite a reduction in upper gut symptoms, total abdominal colectomy and ileorectal anastomosis does not improve delayed gastric emptying in patients with idiopathic slow-transit constipation.

Graves' disease induced by Na(131)I therapy for toxic multinodular goitre.

A 59-year-old woman developed manifestations of Graves' disease several months after treatment with radioiodine (Na(131)) for toxic multinodular goitre. During subsequent treatment with additional radioiodine therapy Graves' ophthalmopathy developed which was severe and required treatment with prednisone and orbital radiotherapy. The literature on development of Graves' disease following Na(131) therapy is reviewed and possible pathophysiological mechanisms are discussed. In this case, possibly the first radioiodine therapy has illicited Graves' thyrotoxicosis and the subsequently added radioiodine treatments for the persistent Graves' thyrotoxicosis led to serious ophthalmopathy. Physicians should recognise Graves-like disease as a complication of Na(131)I therapy for toxic multinodular goitre and carefully consider the timing of consecutive radioiodine therapy.

The effect of cisapride on duodenal acid exposure in the proximal duodenum in healthy subjects.

AIM: To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum. METHODS: Using a double-blind, placebo-controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH-and pressure-recordings were made. Using a small-caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb. RESULTS: Endogenous acidification of the duodenal bulb occurred more frequently during phase II and postprandially, compared to phase I (P<0.001). During phase I, alkalinization of the antrum was observed. Cisapride significantly increased the postprandial number of duodenal acidic periods (P<0.02), but shortened their duration (P<0.04). The duodenal motor response elicited by exogenous acid was lower during phase I (P<0.05). CONCLUSIONS: Antral and proximal duodenal acidity vary with the phases of the interdigestive motor complex. Cisapride shortens the individual periods of duodenal acidification.

Autoimmune hyperthyroidism occurring late after radioiodine treatment for volume reduction of large multinodular goiters.

131I treatment is an effective alternative to surgery in patients with a large, (non-)toxic, compressive goiter. Late development of hyperthyroidism after 131I therapy for nontoxic nodular goiter is considered rare. We have seen this complication in 3 of approximately 80 patients treated with radioiodine for volume reduction of a large, multinodular goiter. Three women, aged 60 to 71 years, had large, multinodular goiters causing tracheal compression. They were clinically euthyroid before 131I therapy and had normal free thyroxine (FT4) levels. Serum thyroid-stimulating hormone (TSH) levels were normal in 2 patients and undetectable in 1 patient. Patients 1 and 2 received a single dose of 86 and 48 mCi 131I, respectively. Patient 3 received 20 mCi 131I twice (interval 1 month). Clinical and biochemical thyrotoxicosis with high thyroid radioactive iodide uptake (RAIU) developed 10, 6, and 3 months after 131I therapy, respectively, although at control visits 1 to 3 months earlier, serum TSH and FT4 levels were normal. Thyrotoxicosis responded well to methimazole in all three patients. The late occurrence of thyrotoxicosis, high RAIU, and good response to methimazole argue against thyroiditis as the cause of thyrotoxicosis. Serum levels of TSH receptor antibodies, which were undetectable before therapy (patients 1 and 2), were clearly elevated in all three patients during thyrotoxicosis. This is in favor of autoimmune hyperthyroidism as the cause of thyrotoxicosis. These cases illustrate that severe autoimmune hyperthyroidism may occur several months after radioiodine treatment for nontoxic, multinodular goiter. Information about symptoms of hyperthyroidism and regular control visits in the first year after therapy are important in these patients.

Radioiodine for nontoxic multinodular goiter.

Surgery is considered standard therapy for nontoxic goiter. However, surgical treatment of large goiters is not without risk, especially in elderly patients and in those with cardiopulmonary diseases. Therefore, in recent years interest in 131I treatment of nontoxic goiter has increased. Studies, using ultrasonography and magnetic resonance imaging (MRI) for accurate measurements of thyroid volume, have shown that 131I treatment of nontoxic nodular goiter results in a mean thyroid volume reduction of 40% after 1 year of 50-60% after 3-5 years. Moreover, an improvement of compressive symptoms can be achieved. This has been objectified by a significant decrease in tracheal compression as measured by MRI. Early side effects due to radiation thyroiditis usually are mild. The development of autoimmune hyperthyroidism occurring several months after 131I therapy in approximately 5% of patients is the most important complication of 131I therapy for nontoxic goiter. The incidence of post-treatment hypothyroidism appears to be approximately 20-30% at 5 years. For elderly people, the lifetime risk of fatal and nonfatal cancer induced by this therapy (administered activity 1.9 +/- 0.9 GBq of 131I) was estimated to be approximately 0.5%. In all patients with nontoxic multinodular goiter the estimated risks of both surgery and radioiodine therapy should be weighed carefully. In younger patients surgery still is to be preferred, especially when the amount of 131I to be administered is high. However, for elderly patients, especially those with cardiopulmonary disease, the profits of radioiodine treatment will outweigh the lifetime risk of this mode of therapy.

Evaluation of antral motility in humans using manometry and scintigraphy.

Recent studies suggest that scintigraphy can be used to evaluate non-invasively antral motility in humans, although scintigraphic techniques have not yet been compared with more conventional measurements of intraluminal pressures by manometry. Simultaneous scintigraphic and manometric measurements of antral motility were performed in nine healthy volunteers. After intubation with a sleeve/sidehole catheter which incorporated five pressure sideholes located at 1.5 cm intervals spanning the antrum, each subject ingested 100 g minced beef labelled with 100 MBq 99mTc-chicken liver and 150 ml water. Between 40-43, 60-63, 80-83, and 100-103 minutes after meal ingestion, radioisotopic data were acquired in two second frames. Time-activity curves showing antral 'contractions' resulting from wall motion were derived by drawing small regions of interest over the antrum to coincide with the position of the antral manometric sideholes. Scintigraphic contraction rates approximated 3/minute, whereas antral pressure waves that occluded the lumen were less frequent (p < 0.01 for all), particularly in the proximal antrum. The amplitude of wall motion, evaluated scintigraphically, and the amplitude of pressure waves were both inversely related to the distance from the pylorus (r > -0.32, p < 0.05) and antral volume r > -0.29 (p < 0.05). There were significant relationships between the amplitude of contractions assessed scintigraphically and the number of lumen-occlusive antral pressure waves in the distal antrum (r -0.48, p < 0.05) but not in the more proximal antral regions. It is concluded that scintigraphy can detect antral wall motion with greater sensitivity than manometry, particularly in the proximal antrum. As manometry gives information on the amplitude as well as the temporal and spatial organisation of those contractions which result in lumen occlusion, the combination of scintigraphic and manometric techniques in the evaluation of antral motility shows considerable promise.

Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenal lipid and antral tachygastria in conscious dog.

The myoelectrical and motor response of the antropyloroduodenal region to intraduodenal nutrient stimulation or antral tachygastria represent useful models for, respectively, physiological and pathophysiological gastric stasis to test the efficacy of prokinetic drugs. We evaluated the effects of an intravenous bolus of cisapride (0.63 mg/kg) on the myoelectrical and motor response of the antropyloroduodenal region to an intraduodenal triglyceride emulsion (10% Intralipid, 0.5 ml/min) or antral tachygastria in conscious dogs. Intraduodenal lipid suppressed antral motility (P < 0.05, compared to intraduodenal saline) and stimulated phasic pyloric contractions (P < 0.01, compared to intraduodenal saline), a motor pattern known to be associated with delayed gastric emptying. During intraduodenal lipid stimulation cisapride virtually abolished all isolated pyloric motor events (P < 0.05) and stimulated antral and duodenal motility (P < 0.05 for both) and antropyloroduodenal coordination (65% versus 15%; P < 0.05). Antral tachygastria was associated with a higher number of isolated pyloric motor events in the fasted state [0.8 (0.7-1.1) per minute versus 0.2 (0-0.3) per minute; P < 0.05], but not during intraduodenal lipid stimulation [1.1 (0.9-1.7) per minute versus 1.2 (1.0-1.9) per minute; NS]. Cisapride decreased the number and duration of spontaneous episodes of antral tachygastria during intraduodenal saline and lipid infusion (P < 0.05 for both) and abolished the tachygastria-associated motor patterns. Cisapride induced a 20% decrease in the antral slow-wave frequency during intraduodenal saline and lipid, irrespective of gastric pacemaker rhythm. We conclude that: (1) cisapride overcomes feedback from small intestinal lipid receptors on myoelectrical and motor activities of the antropyloroduodenal region and decreases antral slow-wave frequency, and (2) cisapride inhibits antral tachygastria and tachygastria-associated motor patterns. These effects may contribute to the effective gastrokinetic properties of cisapride in physiological and certain forms of pathophysiological gastric stasis.

Relationship between surface electrogastrography and antropyloric pressures.

The cutaneous electrogastrogram (EGG) and intraluminal antropyloroduodenal pressures were recorded in 12 healthy volunteers for 30-min periods during phase II of the interdigestive motor complex, during intraduodenal infusion of 10% triglyceride, and after intravenous erythromycin (3 mg/kg). During phase II, the frequency of the EGG was relatively constant in each individual, with a median frequency of 0.046 Hz [2.8 counts per minute (cpm)]. EGG frequency was greater (P < 0.05) than the median rate of antral pressure waves (1.8 cpm). The suppression of antral pressure waves (P < 0.05) and stimulation of isolated pyloric pressure waves (IPPWs) (P < 0.05) produced by triglyceride infusion were not associated with changes in EGG frequency compared with phase II. The frequency of the EGG and the rate of IPPWs were comparable. After erythromycin, EGG frequency was 0.03 Hz (1.8 cpm), less than during both phase II and triglyceride infusion (P < 0.05) and almost identical to the rate of antral pressure waves. Pressure waves were nearly always associated with an EGG signal. In contrast, the temporal relationship between the EGG signal and pressure waves was variable. During triglyceride infusion (r = 0.83, P < 0.001) and after erythromycin (r = 0.83, P < 0.001) there was a close (approximately 1:1) relationship between the rate of pressure waves and EGG frequency. However, there was no significant relationship (r = 0.32, not significant) between the number of pressure waves and EGG frequency frequency during pase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereospecific effects of intraduodenal tryptophan on pyloric and duodenal motility in humans.

BACKGROUND: L-Tryptophan delays gastric emptying in animals to a greater extent than D-tryptophan, but none of the possible motor mechanisms responsible for this stereospecific effect have been evaluated. METHODS: In 11 healthy volunteers antropyloroduodenal pressures were recorded in the fasted state with a sleeve/sidehole manometric assembly during 20-min intraduodenal infusions (2 ml.min-1) of isotonic L- and D-tryptophan (50 mM, pH 5.7) and normal saline (pH 5.5), given in randomized order. RESULTS: Intraduodenal L-tryptophan increased basal pyloric pressure (p < 0.05), whereas D-tryptophan had no effect. In contrast, L- and D-tryptophan both stimulated (p < 0.05) localized phasic pyloric pressure waves, and there was no significant difference in the responses. The number of duodenal pressure waves was greater during infusion of L-tryptophan than during D-tryptophan (p < 0.05). CONCLUSION: We conclude that intraduodenal tryptophan has stereospecific effects on pyloric and duodenal motility. Although the precise contribution of these differential effects to gastric emptying remains to be clarified, they may be partially responsible for the differences in gastric emptying of D-tryptophan and L-tryptophan.

Stereospecific effects of tryptophan on gastric emptying and hunger in humans.

The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L-enantiomer. The effects of D- and L-tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L-tryp (50 mmol/L), D-tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at -2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L-tryp and D-tryp (P < 0.05) and D-tryp emptied faster than L-tryp (P < 0.005). Emptying from the proximal stomach was fastest for saline (P < 0.05) and faster for D-tryp than L-tryp (P < 0.005). Emptying from the distal stomach was faster for saline than both D- and L-tryp (P < 0.05). A reduction in hunger (P < 0.05) and a non-significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L-tryp than after ingestion of D-tryp (P < 0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.

Effects of duodenal distention on fasting and postprandial antropyloroduodenal motility in humans.

BACKGROUND/AIMS: Mechanoreceptors in the proximal small intestine may play an important role in the regulation of gastric emptying. Balloon distention of the duodenum causes fundic relaxation. The purpose of the present study was to determine the effect of stimulation of duodenal mechanoreceptors on both fasting and postprandial antropyloroduodenal motility in humans. METHODS: Antropyloroduodenal pressures were recorded in 12 healthy volunteers with a sleeve-sidehole assembly, incorporating two balloons 5 and 20 cm distal to the pylorus. Duplicate proximal and distal duodenal balloon distensions with 10, 20, and 30 mL of air for 2.5 minutes were performed separately and in randomized order both during fasting and after a meal. RESULTS: During fasting, proximal and distal distention at all volumes increased the number of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05), and the response to proximal distention was greater (P < 0.05). Postprandially, proximal and distal distention increased basal pyloric pressure (P < 0.05) with a greater response to proximal distention (P < 0.05), but had no effect on isolated pyloric pressure waves. Both during fasting and postprandially, there were more synchronous and less antegrade antral waves during distention (P < 0.05). The number of duodenal pressure waves increased during proximal (P < 0.05) but not distal distention. CONCLUSIONS: Stimulation of duodenal mechanoreceptors by balloon distention has significant and region-dependent effects on antropyloroduodenal motility that vary between fasting and postprandial states.

Listeria meningitis presenting as enteritis in a previously healthy infant: a case report.

A previously healthy 1-year-old infant was admitted with pyrexia and mild gastro-intestinal symptoms. A blood culture, taken on admission, showed growth of Listeria monocytogenes (serotype 4b) on the 3rd day, at which time a lumbar puncture revealed a listeric meningitis. Despite the delay of antibiotic treatment, the infant never showed any neurological symptoms. She recuperated without any residual effects.

Pyloric motility. Sleeve sensor versus strain gauge transducer.

Intraduodenal infusion of nutrients has been shown by intraluminal sleeve-sidehole manometry to suppress antral contractions and stimulate isolated pyloric pressure waves (IPPWs) in humans. It is still unresolved, whether these pyloric contractions occur within an otherwise quiescent zone of motor and electrical activity and whether the presence of the sleeve sensor itself affects this nutrient-associated response. In four conscious dogs, comparisons were made between paired recordings of myoelectrical and motor activities of the antropyloroduodenal region with serosal strain gauge transducers and extracellular bipolar electrodes in the presence and absence of an intraluminal manometric sleeve-sidehole assembly during intraduodenal infusions of saline and a triglyceride emulsion (Intralipid 10%, 0.5 kcal/min). Of 287 isolated pyloric pressure waves, detected by the manometric sleeve sensor, 75% were detected as isolated pyloric contractions by the strain gauge transducers and 72% occurred in the absence of electrical spike activity in the distal antrum or proximal duodenum. The lower incidence of isolated pyloric contractions (strain gauges) was related to: (1) insensitivity of the pyloric strain gauge transducer in comparison to the manometric sleeve sensor (10%), and (2) inability of the manometric sleeve-sidehole assembly to detect pressure waves in the distal antrum (7%) or proximal duodenum (8%) during antral or duodenal wall motion. The presence of the sleeve sensor itself did not affect the number of lipid-induced isolated pyloric contractions but increased their amplitude [median 9 (7-15) mN vs 4 (2-6) mN; P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite.

BACKGROUND: It is uncertain whether gastric emptying of fat is determined mainly by its physical characteristics or chemical composition. In particular, the intragastric distribution of extracellular fat and the importance of that distribution to gastric emptying of fat is controversial. The effects of posture on gastric emptying, intragastric distribution, and appetite after ingestion of a meal containing oil and aqueous phases was evaluated. METHODS: Eleven volunteers consumed 60 mL 99mTc-(V)-thiocyanate-labeled olive oil and 290 mL 113mIn-labeled soup while sitting and while lying in the left lateral decubitus position. Hunger before and after the meal was recorded. RESULTS: In the sitting position, oil emptied from the stomach more slowly (P < 0.01) whereas in the decubitus position oil emptied faster (P < 0.01) than the aqueous phase. Oil was preferentially retained in the proximal stomach when sitting (P < 0.01), and more oil was retained in the distal stomach in the decubitus position (P < 0.05). The amount of oil that emptied in the first 180 minutes was not different between the two postures. The aqueous phase emptied much more slowly (P < 0.01) in the decubitus position. At 120 minutes and 180 minutes, subjects were less hungry (P < 0.05) in the decubitus position. In the decubitus position, hunger at 120 minutes and 180 minutes was related to the retention of oil (r > or = 0.79; P < 0.01) in the stomach. CONCLUSIONS: These results indicate that (1) gravity has a major effect on the intragastric distribution and relatively little effect on total stomach emptying of oil, and (2) postprandial hunger is affected by posture and, in the decubitus position, is inversely related to the amount of oil that has entered the small intestine.

Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects.

The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa.

Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects.

Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.