Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication.

BACKGROUND: This study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD). SUBJECTS AND METHODS: In 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication. RESULTS: In the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120-180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004). CONCLUSIONS: After fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

Globus sensation: pharyngoesophageal function, psychometric and psychiatric findings, and follow-up in 88 patients.

BACKGROUND: The globus sensation has been widely regarded as psychogenic, but organic disorders were found to be etiologically significant. OBJECTIVE: To investigate the structural, functional, psychological, and psychiatric factors possibly eliciting the globus sensation and influencing its course. METHODS: Eighty-eight patients, 67 women and 21 men (aged 22-71 years), referred to 2 tertiary care centers underwent history taking, otolaryngological examination, pharyngoesophageal videofluoroscopy and manometry, psychosocial evaluation, psychometric tests, psychiatric interview, and when indicated, esophagogastroduodenoscopy, esophageal bolus transport, gastroesophageal reflux, and gastric emptying studies. According to revealed disorders, therapy was initiated, and the outcome was studied. RESULTS: Only 15 patients had normal pharyngoesophageal function; of these 15, 6 had chronic tonsillitis or pharyngitis, 3 had thyroid adenomata, 4 had cervical spondylosis, and 1 each had dry oropharyngeal mucosa and chronic bronchitis. Of the other 73 patients, 2 had pharyngeal dysfunction, 24 had achalasia, 1 had diffuse esophageal spasms, 3 had "nutcracker esophagus," 30 had nonspecific esophageal motor disorders, and 13 had gastroesophageal reflux. Psychometry revealed no more anxiety and depression than in general medical outpatients. Of 58 patients interviewed, 37 met criteria for psychiatric disorders. Psychometric scores and psychiatric characteristics were unrelated to the sensation's course. Therapy was recommended, but only 26 patients were treated accordingly; 22 received nonspecific treatment. Follow-up 3 to 59 months later revealed that the sensation had vanished in 13 patients who had received specific treatment, 5 who had received nonspecific treatment, and 6 who had received no treatment; it was alleviated in 10 who had received specific treatment, 13 who had received nonspecific treatment, and 9 who had received no treatment; and it was unchanged in 3 who had received specific treatment, 5 who had received nonspecific treatment, and 23 patients who had received no treatment. CONCLUSIONS: Pharyngoesophageal disorders may be sensed only vaguely, inducing the globus sensation. Psychological and psychiatric characteristics could be relevant to the discomfort experienced but are unlikely to be etiologically significant.

Slow gastric emptying in type I diabetes: relation to autonomic and peripheral neuropathy, blood glucose, and glycemic control.

OBJECTIVE: To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18-75 years; illness duration 3-46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying. RESULTS: The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly greater than that of 48 healthy subjects, that is, 71.1 +/- 15.1 vs. 53.5 +/- 13.1% [means +/- SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients. CONCLUSIONS: Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.

Cisapride versus placebo for 8 weeks on glycemic control and gastric emptying in insulin-dependent diabetes: a double blind cross-over trial.

In insulin-dependent diabetes mellitus, slow gastric emptying may make absorption unpredictable and foster glycemic instability. Cisapride accelerates emptying, but controlled long term studies are scarce, and effects on glycemic control unknown. We investigated, in patients with insulin-dependent diabetes mellitus and unstable glycemia, the effects of 10 mg cisapride 4 times daily for 8 weeks vs. placebo on glycemic control and gastric emptying under random, cross-over, double blind conditions. In 14 patients with delayed and 9 with nondelayed emptying, blood glucose variability over 28-week treatment periods separated by a 4-week wash-out and gastric emptying of a semisolid 1168-kJ meal immediately after the treatment periods were assessed. Cisapride did not affect glycemic control [SD of within-patient mean blood glucose, 4.2 mmol/L +/-0.1 (+/- SEM) vs. 4.0+/-0.1 mmol/L after placebo; hemoglobin A1c, 8.3+/-0.2% vs. 8.5+/-0.2%]. Emptying was faster after cisapride than after placebo in 8 of 14 patients with delayed vs. 7 of 9 with nondelayed emptying (P = NS) and in 11 of 15 without vs. 4 of 8 with cardiovascular autonomic neuropathy (P = NS). Autonomic neuropathy prevailed in 7 of 14 patients with delayed and 1 of 9 with nondelayed emptying. Blood glucose immediately before and during assessment of emptying was unrelated to the emptying rate, whereas blood glucose increases over fasting levels were greater with faster emptying (P<0.002). In conclusion, cisapride's effects were not different from those of placebo on glycemic control and gastric emptying, it did not differently affect patients with delayed vs. nondelayed emptying, and it slightly accelerated emptying (P = NS) in patients without, but not in those with, cardiovascular autonomic neuropathy. Blood glucose levels before and during assessment of emptying did not affect emptying, but the glucose rise over fasting levels was greater with faster emptying.

Relationship between thresholds to thermally and to mechanically induced pain in patients with eating disorders and healthy subjects.

This paper presents the results of a correlation analysis comparing thresholds to thermally and to mechanically induced pain in 40 patients with eating disorders and 32 healthy control subjects. The correlation coefficients for the response to the two modalities of pain were 0.498 for the whole sample, 0.430 for the healthy subjects, and 0.402 for the patients with eating disorders. Although these results indicate a significant overlap in the individuals' responses to the two modalities of induced pain, the criterion suggested by Janal et al. (Pain, 58 (1994) 403-411) of a "minimum correlation of 0.5 (that) would justify allowing one test to be considered equivalent to another' is not met.

Gastric emptying of semisolid meal unaltered by 3 days' administration of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate.

BACKGROUND: Evidence has accumulated that nitric oxide is involved in the regulation of gastrointestinal motor activity. We investigated whether nitric oxide derived from a sustained-release isosorbide dinitrate (Cedocard retard) had an effect on gastric emptying and on subjective feelings. METHODS: Twelve healthy males aged 23-32 years received at weekly intervals, for 3 days twice daily, either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate, or placebo, under random double-blind conditions. After a further dose on day 4, subjects ate a 1168 kJ semisolid meal, the emptying of which was recorded scintigraphically for 50 min. RESULTS: Neither dosage of isosorbide dinitrate had an effect on emptying which differed from the effect of placebo and the effects of the two dosages were the same. The radioactivity remaining in the stomach 50 min postprandially was 68.5% +/- 4.5 S.E.M. after placebo, 65.4 +/- 5.6% after 20 mg isosorbide dinitrate and 66.1 +/- 4.4% after 40 mg isosorbide dinitrate. With 40 mg isosorbide dinitrate, all 12 subjects complained of persistent headache, whereas only slight headache was reported by 7 subjects on 20 mg isosorbide dinitrate and by 1 subject on placebo. CONCLUSION: Twenty and 40 mg doses of sustained-release isosorbide dinitrate twice daily had no effect on the gastric emptying of a semisolid meal, but dose-dependently induced headaches.

Sublingual nitroglycerine: effects on contractile activity of the distal oesophagus and lower oesophageal sphincter in healthy men.

BACKGROUND AND AIMS: Nitric oxide plays an important role in the control of gastrointestinal motility. This study assessed the effects of graded doses of the nitric oxide-releasing agent, nitroglycerine, on distal oesophageal motor activity and lower oesophageal sphincter resting pressure. METHODS: Eight healthy young men received at 1-week intervals placebo, 0.2 mg, 0.4 mg or 0.8 mg nitroglycerine sublingually under random double-blind conditions. Sphincter pressure was recorded using a Dent sleeve and oesophageal motility using sensors 1, 4, 7 and 10 cm orad the sleeve during two 15-min periods before and four 15-min periods after drug administration. In minutes 4 to 6 of each period, subjects swallowed 5 mL water at 30 s intervals. RESULTS: After 0.2 mg and 0.4 mg nitroglycerine, amplitude, duration and area under curve of swallow-initiated contractions were smaller than after placebo. After 0.8 mg nitroglycerine, amplitude, duration and area under curve were slightly greater than after placebo and significantly greater than after the lower nitroglycerine doses. No effects were discernible on onset latency and propagation velocity of contractions as well as on lower oesophageal sphincter resting pressure. CONCLUSIONS: Sublingual nitroglycerine had modest, dose-dependent effects on oesophageal peristaltic amplitude and duration, but did not affect the tone of the lower oesophageal sphincter.

Effects of 3-days' intake of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility.

BACKGROUND: Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained-release preparation of the nitric oxide donor isosorbide dinitrate on swallow-initiated oesophageal contractions and the lower oesophageal sphincter. METHODS: Twelve healthy men, aged 23-32 years, received, at 1-week intervals and under random double-blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side-hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5-mL water swallows were evaluated. RESULTS: Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg +/- 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 +/- 1.0 mmHg) than after placebo (17.9 +/- 1.7 mmHg; P < 0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo. CONCLUSIONS: Twenty and 40 mg sustained-release isosorbide dinitrate twice daily had no effect on swallow-initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.

Effects of cholecystokinin and caerulein on human eating behavior and pain sensation: a review.

Since the mid-1970s, evidence has accumulated that cholecystokinin (CCK) has a role as a neuromodulator or neurotransmitter in the central nervous system as well as in the periphery. CCK has been shown to have a variety of effects on gastrointestinal functions and is one of the main candidates for a role as a peripheral negative feedback signal to stop feeding behavior. CCK produces satiety not only in animals but also in man: it reduces appetite and activation arising from the preparation of a meal and inhibits intake of liquid and solid food in both lean and obese subjects. The closely related peptide caerulein has similar effects. The site of action of peripherally administered CCK seems to be on an abdominal organ innervated by gastric vagal branches and relayed to the brain by afferent vagal fibres, since selective gastric vagotomy blocks the satiety effect, but pharmacological antagonism of vagal motor effects or lesions of the ventromedial hypothalamus do not. CCK also may have a role in the regulation of pain perception. In mice, CCK and caerulein were shown to produce a decrement in response to noxious stimulation after peripheral and central administration. In man, caerulein was demonstrated to relieve pain originating from biliary and renal colic as well as from cancer and ischemia. A series of studies in healthy man revealed that caerulein also alleviates experimentally induced cutaneous pain. Data from animal studies suggest that CCK-like peptides not only are able to produce analgesic effects on their own, but also are involved in the modulation of opioid systems mediating analgesia. Further study of these effects of CCK should elucidate the regulatory connections between the life-sustaining functions of feeding and pain sensation.

Cilansetron. Solvay.

Cilansetron is a 5-HT3 antagonist tinder development by Solvay Pharmaceuticals as a potential treatment for irritable bowel syndrome (IBS). The compound targets non-constipated men and women with IBS. Cilansetron is being evaluated in phase III trials, but up to now, only scarce information has been made available and most publications have appeared in abstract form only. In July 2001, it was reported that regulatory submissions were expected in 2003 [416185]. Also in July 2001, after discussion with the FDA, Solvay initiated a revised phase III program in diarrhea-predominant IBS and signed a five-year 'preferred-provider' clinical services agreement with Quintiles Transnational to conduct the trial. At this time, Solvay was also seeking marketing partners for cilansetron [416185]. By October 1999, Solvay was treating cilansetron as one of its main priorities, as it represented a novel class of compound [342434]. Solvay has predicted peak sales of euro 100 m to euro 1000 m [420654].

Satiety effects of cholecystokinin and ceruletide in lean and obese man.

Cholecystokinin (CCK) has been shown to produce satiety not only in a variety of animal species but in man as well. In healthy humans, CCK reduces appetite and activation arising from the preparation of a meal, inhibits intake of liquid food in both non-obese and obese subjects, and decreases the intake of solid food. The closely related caerulein produces a similar reduction of solid food consumption in lean and, as suggested by preliminary results, in obese man. There is good evidence that the satiety effect of CCK depends on its inhibition of gastric emptying and the consequent gastric distension. In healthy man, the same dose of caerulein found to reduce food intake also slows gastric emptying of a semisolid meal. This effect seems to be relayed into the brain by afferent vagal fibers as in animals; selective gastric vagotomy blocks the satiety effect while pharmacological antagonism of vagal motor effects or lesions in the ventro-medial hypothalamus do not. Ongoing studies suggest that gastric vagotomy also blocks the satiety effects of caerulein in man. A critical role for CCK in the control of human feeding behavior seems certain.

Achalasia. Results of myotomy and antireflux operation after failed dilatations.

OBJECTIVE: To evaluate the outcomes of patients with achalasia who had undergone myotomy and an antireflux operation because dilatations had not yielded satisfactory results. DESIGN: Retrospective analysis. SETTING: University-based tertiary care center. PATIENTS: Of 39 patients who met inclusion criteria, 18 female patients and 18 male patients (age range; 17-85 years; median age, 54 years; range of time elapsed since operation, 1-22 years; median time, 6 years) could be studied. Antireflux operations included 360 degrees fundoplications in 27 patients, anterior hemifundoplications in 5 and other procedures in 4. MAIN OUTCOME MEASURES: Dysphagia for solid foods and liquids, regurgitation, heartburn, retrosternal pain and body weight. RESULTS: Excellent, good, and fair results of myotomy and antireflux operation were encountered in 14, 3, and 6 patients, respectively, and poor or absent results in the remaining 13 patients. The resting pressure of the lower esophageal sphincter was significantly lower at follow-up than preoperatively, and this was associated with reduced dysphagia for solid foods in 14 patients and for liquids in 16 of 17 patients. CONCLUSIONS: Myotomy and antireflux operation yielded excellent to fair results in 23 patients in whom dilatations had not facilitated swallowing. Poor results in the remaining 13 patients seemed to be attributable to the 360 degrees fundoplication performed in 12 of them. In these patients, a further surgical intervention seemed to be indicated.

Ceruletide decreases food intake in non-obese man.

Cholecystokinin decreases food intake in animals and in man. This study investigated whether the structurally related ceruletide reduces food intake in healthy non-obese man. Twelve females and 12 males participated, after an over-night fast, in each of two experiments. During the basal 40 min, saline was infused IV. Thereafter, the infusion was, in random double blind fashion, either continued with saline or switched to 60 or 120 ng/kg b. wt/hr ceruletide. Butter was melted in a pan and scrambled eggs with ham were prepared in front of the subjects, who were instructed to eat, together with bread and mallow tea, as much as they wanted. With 120 ng/kg/hr ceruletide, the subjects ate significantly less (16.8 percent) than with saline (3725 kJ +/- 489 SEM and 4340 kJ +/- 536, respectively; p less than 0.025). They also reported less hunger (p less than 0.005) and activation (p less than 0.005) and activation (p less than 0.01), and had longer reaction times (p less than 0.01) and a weaker psychomotor performance (p less than 0.025). 60 ng/kg/hr ceruletide decreased food intake only slightly (6.6%; 3089 kJ +/- 253 and 3292 kJ +/- 300 respectively) and no significant changes in the above measures occurred. In conclusion, ceruletide reduces food intake in man, thus resembling the effects of cholecystokinin.

Ceruletide increases threshold and tolerance to experimentally induced pain in healthy man.

UNLABELLED: Previous studies suggested that ceruletide might be endowed with analgesic and sedative properties. To investigate the effects of ceruletide on experimentally induced pain and on central nervous functions, two studies, each involving 24 healthy subjects, were carried out in random double-blind fashion. Every subject participated in three experiments one week apart. In study 1, 120 and 60 ng/kg/hr ceruletide IV increased threshold and tolerance to electrically and threshold to thermally induced cutaneous pain significantly more than saline (p less than 0.001), the higher dose being slightly more active. Only mild sedative effects occurred. Study 2 compared the effects of 60 and 6 ng/kg/hr ceruletide IV to those of 0.4 mg/kg/hr pentazocine IV and investigated whether these effects were naloxone reversible. Both ceruletide doses, 60 ng/kg/hr slightly more than 6 ng/kg/hr, elevated threshold and tolerance to electrically induced and threshold to thermally induced pain markedly, pentazocine acted stronger and longer than ceruletide (p less than 0.001). Naloxone reversed the effects of pentazocine but not of ceruletide. CONCLUSION: ceruletide (1) exerts potent naloxone resistant analgesic effects, which, however, are inferior to those of pentazocine, and (2) produces only mild sedation.

Cholecystokinin octapeptide decreases intake of solid food in man.

Cholecystokinin octapeptide (CCK-OP) was reported to decrease the intake of liquid food in lean and in obese man. This study investigated the effect of CCK-OP on the consumption of real life food, i.e., of standardized sandwiches. Sixteen young non-obese females and males participated, after an overnight fast, each in two experiments. After a basal 30 min, saline or CCK-OP, 1.5 or 3.0 Ivy Dog Units/kg body weight/15 min, was infused in random double blind fashion, while sandwiches were placed in front of the subjects. For the next three 15-min periods, the subjects were instructed to eat as much as they liked. In the first 15 min after 3.0 as well as 1.5 U CCK-OP/kg/15 min significantly fewer sandwiches (50 and 17 percent) were eaten than after saline (p less than 0.01 and p less than 0.05) and less hunger was reported (p less than 0.02 and p less than 0.05). Self-reported activation decreased only with 3.0 U CCK-OP (p less than 0.005). Reports of well-bring , electroencephalogram, heart rate, and respiration were not altered. The results support the notion that CCK is involved in the regulation of food intake.

Efficacy of cyclosporin A in systemic sclerosis.

In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA-administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed.

Pain sensitivity, alexithymia, and depression in patients with eating disorders: are they related?

A decreased sensitivity to painful stimuli and high scores for alexithymia and depression have been observed in patients with eating disorders. We investigated the relationship between these factors in 22 patients with anorexia nervosa, 18 patients with bulimia nervosa, and 32 healthy subjects. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale and depression using the Beck Depression Inventory. Patients with bulimia exhibited significantly higher thresholds to mechanically induced pain than healthy subjects. Thresholds to thermally induced pain in patients with anorexia or bulimia were similar and significantly higher than in the healthy subjects. Alexithymia and depression scores were significantly higher in anorexic and bulimic patients than in the healthy subjects. Analyses of covariance revealed that the degree of alexithymia did not influence thresholds to thermally and mechanically induced pain, whereas the severity of depression affected to some extent the threshold to thermally induced pain.

Epigastric fullness.

Epigastric fullness may be caused by a disordered gastric motor function, resulting in delayed gastric emptying, but may also be caused by rapid emptying, leading to a distention of the proximal small intestine. A rational diagnostic approach to a patient complaining of epigastric fullness is needed to reveal the underlying disorder or disease and to enable an adequate, targeted therapy. The clinical impression based on symptoms is unreliable and cannot distinguish function disorders and benign disease from severe conditions.

Stimulatory effects of the synthetic enkephalin analogue FK 33-824 on colonic motor activity antagonized by naloxone.

Enkephalins inhibit guinea pig ileum contractions in vitro; in vivo they increase gastric contraction strength and small intestinal spike activity in dogs and stimulate tonic and phasic contractile activity of the human colon. This study investigated the question as to whether the stimulatory effect of the synthetic met-enkephalin analogue FK 33-824 on the human colon is antagonized by the narcotic antagonist naloxone. On 3 experimental days 12 healthy young males received in random order (a) 4 mg (subjects 1-6) or 10 mg (subjects 7-12) naloxone i.v. followed by 1 mg FK 33-824 i.m., (b) saline i.v. followed by 1 mg FK 33-824 i.m. and (c) saline i.v. followed by saline i.m. FK 33-824 following saline produced a rapid increase of tonic intraluminal pressure (mean increase: 9.9 +/- 2.5 SEM mmHg; P less than 0.001), an increase in contractions from 1.6 +/- 0.4 to 3.3 +/- 0.8 per min (P less than 0.001), a shift in the dominant frequency of rhythmic contractions from 1.0 +/- 2.5 to 2.5-3.5 cycles per min, an increase in the amplitude of contractions from 10.1 +/-0 2.1 to 15.0 +/- 3.2 mmHg (P less than 0.01), and in the sum of the amplitudes as an overall measure of contractile activity from 148.6 +/- 36.7 to 482.9 +/- 136.9 mmHg (P less than 0.01). All effects lasted for more than 70 min; peak changes occurred in the first 15 min and subsided slowly in intensity. The effects of FK 33-284 were greatly attenuated by premedication of 4 mg naloxone, and abolished, at least for 15-30 min, by 10 mg naloxone. Saline caused no changes. It is concluded that the stimulatory effects of FK 33-824 on human colonic motility are antagonized by naloxone.

Effects of the 5-HT3 receptor antagonist, ICS 205-930, on oesophageal motor activity and on lower oesophageal sphincter pressure: a double-blind cross-over study.

The selective 5-HT3 receptor antagonist, ICS 205-930 (Sandoz), has potent effects on gastrointestinal motor activity in vitro and in vivo. This double-blind, crossover study compared the effects of 20 mg of ICS 205-930 infused intravenously with those of a placebo on the motor activity of the oesophageal body and the lower oesophageal sphincter (LOS). Each of twelve healthy young men participated in two recording sessions one week apart. Oesophageal pressures were recorded using a catheter assembly with orifices 2, 5, 8, 11, and 14 cm above the oral border of the LOS and a Dent sleeve for measurement within the LOS. During and after the infusion of ICS 205-930, amplitude and duration of swallow-initiated contractions in the smooth muscle oesophagus increased slightly, the area under the curve as a measure of contraction strength being significantly greater than after placebo (P less than 0.05). LOS resting pressure increased slightly during ICS 205-930 infusion and was significantly higher than it was in the case of the placebo (P less than 0.001). Propagation velocity of contractions, incidence of tertiary contractions and relaxation of LOS upon swallowing remained unaffected. ICS 205-930 was well tolerated. It is concluded that ICS 205-930 has slight but distinct stimulatory effects on contraction strength in the smooth muscle oesophagus and LOS resting pressure.