Epstein-Barr virus associated gastric carcinoma: the genetic alteration and the expression of CD44 variant

BACKGROUND: Chronic symptomatic gastroparesis occurs in 3-5% of patients following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves gastric emptying in patients with idiopathic and diabetic gastroparesis. Erythromycin's effect on gastric emptying in patients with post-vagotomy-antrectomy gastroparesis is unknown. The aim of this study was to determine if a single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis. METHODS: Six patients were entered into the study, three males and three females, with a mean age of 50 years. Four patients were randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean time since initial surgery was 9.2 years (range 1-16 years) with five patients having undergone a Roux-en-Y revision. RESULTS: Intravenous erythromycin significantly lowered percentage gastric retention at 120 min, from a baseline of 90.5 +/- 6% (S.E.M.) to 40.1 +/- 4.8% after erythromycin (P = 0.0002). Erythromycin improved gastric emptying in each patient by at least 40%. Intravenous erythromycin significantly accelerated the rate of gastric emptying in the first 30 min after meal ingestion from a baseline rate of 0.072 +/- 0.06%/min to 0.96 +/- 0.31%/min after erythromycin (P = 0.028). For each of the subsequent 30 minute time periods, erythromycin had no significant effect on the rate of gastric emptying. CONCLUSION: Intravenous erythromycin significantly improves the initial phase of solid meal gastric emptying in patients with chronic symptomatic post-antrectomy-vagotomy gastroparesis.     

PEDB: the Prostate Expression Database

Naloxone is generally considered to be a pure antagonist, but it may produce several behavioral effects, such as hyperalgesia or stimulation of respiration. We studied the effect of naloxone on gastric emptying and gastrointestinal transit in rats. Six to eight Wistar rats (200-250 g) were used for each experiment. Either saline or naloxone (0.01-10 mg/kg) was injected intraperitoneally at 0 min. At 30 min, radiolabeled saline or milk 1 mL was infused into the stomach. At 60 min, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. Naloxone significantly inhibited gastric emptying of saline (P = 0.002) and of milk (P < 0.05), but not the gastrointestinal transit of either (P > 0.05). Gastric emptying of saline showed a significant peak (P < 0.05) in the dose-response curve at 0.7 mg/kg. Therefore, naloxone significantly inhibits gastric emptying of saline and milk, but not the gastrointestinal transit of either. IMPLICATIONS: Although naloxone is generally considered to be a pure opioid receptor antagonist, it delays gastric emptying of saline or milk, as does morphine in the rat. However, it is uncertain from our results whether naloxone inhibited gastric emptying by antagonizing the effects of endogenous opioids.     

Anaphylaxis to erythromycin

BACKGROUND: Erythromycin and its salts belong to the larger class of macrolides. Erythromycin is well tolerated. The most common side effects are gastrointestinal distress, nausea, and vomiting, which are dose related. Allergic and pseudoallergic reactions due to macrolide antibiotics are uncommon. Anaphylaxis and acute respiratory distress appear in the literature as case reports. METHODS: We report a 24-year-old man who presented 12 years ago a systemic allergic reaction to penicillin, confirmed by skin tests and detection of specific IgE (RAST). Since then he had tolerated erythromycin on several occasions. Nine months ago, his general practitioner prescribed erythromycin orally as treatment for a respiratory infection. Thirty minutes after taking the first dose, 500 mg, he developed an anaphylactic reaction. The episode subsided with treatment with high dose corticosteroids, antihistamines, and epinephrine. Skin prick tests and intradermal tests were performed with erythromycin at different concentrations. We also measured total IgE and specific IgE to erythromycin by CAP and Phadezym RAST (Pharmacia, Uppsala, Sweden), respectively. We also performed a Prausnitz-Küstner test (PK test), and oral challenge test. RESULTS: Skin testing to erythromycin was not helpful because of cutaneous hyperreactiviness. No significant levels of specific IgE to erythromycin were detected. The oral challenge and the Prausnitz-Küstner test were positive. CONCLUSIONS: The positive history and oral challenge test suggested an anaphylactic reaction to erythromycin. The positive Prausnitz-Küstner test demonstrated the presence of specific IgE to erythromycin.     

Effects of intravenous erythromycin on antroduodenal motility in humans: non-invasive observations with real-time ultrasound

Erythromycin has been shown to act on motilin receptors on gastrointestinal smooth muscle in vitro and to accelerate gastric emptying in normal subjects as well as in patients with diabetic mellitus. To evaluate the motor pattern that accounts for this accelerated emptying, the effects of 12.5 mg/min erythromycin vs. placebo on postprandial motility of the antroduodenum was examined with real-time ultrasound in 15 normal subjects. During 10 minutes of observation, erythromycin significantly increased forward transpyloric flow episode (1.04 +/- 0.19 vs. 0.37 +/- 0.41; p < 0.05), forward transpyloric flow duration (5.79 < 4.49 vs. 3.19 < 1.72 seconds; p < 0.05) and improved antro-pyloro-duodenal coordination (0.43 +/- 0.23 vs. 0.21 +/- 0.17; p < 0.05). However, no significant differences were found for gastric peristaltic cycle (22.62 +/- 3.06 vs. 23.40 +/- 2.14 seconds; p > 0.05), retrograde transpyloric flow episode (0.13 +/- 0.16 vs. 0.18 +/- 0.29; p > 0.05), and retrograde transpyloric flow duration (1.24 +/- 0.30 vs. 1.38 +/- 0.58 seconds; p > 0.05). We conclude that erythromycin increases episode and duration of forward transpyloric flow, and improves antro-pyloro-duodenal coordination, which may play a role in accelerating gastric emptying.     

Effect of bethanechol or erythromycin on gastric emptying in horses

OBJECTIVE: To investigate the prokinetic effect of bethanechol and erythromycin in the upper gastrointestinal tract of healthy horses by measuring the gastric emptying (GE) rate of a radioactive meal. ANIMALS: 4 healthy adult horses. PROCEDURE: After food was withheld for 12 hours, horses were given 370 MBq of 99mTc-labeled sulfur colloid incorporated into egg albumen and 37 MBq of 111In-labeled diethyltriaminepentaacetic acid in 120 ml of water via nasogastric intubation. Intravenously administered treatments were 0.9% NaCl solution, erythromycin (0.1 or 1.0 mg/kg of body weight), or bethanechol (0.25 mg/kg). All drugs were given in 10 ml of 0.9% NaCl solution. Dual-phase scintigraphic images were obtained by use of a gamma camera. The best-fit function was determined for each study, and the resultant curves were then analyzed by use of least squares nonlinear regression. Two variables, time to 50% emptying of the stomach (T-50) and slope of the emptying curve, were derived from the calculated power exponential equation. CONCLUSIONS: Treatment had a significant (P < 0.05) overall effect on T-50 of solid-phase GE. The T-50 of bethanechol (30.09 +/- 10.01 minutes), erythromycin at 0.1 mg/kg (59.08 +/- 10.01 minutes), and erythromycin at 1 mg/kg (60.50 +/- 10.01 minutes) were significantly shorter than T-50 after saline administration (89.97 +/- 10.01 minutes). There was a trend (P = 0.09) for the slope of solid-phase GE of bethanechol and erythromycin (0.1 mg/ kg; P = 0.37) to be steeper than that of saline solution. For liquid-phase GE, the T-50 and the slope of bethanechol differed significantly (P < or = 0.05) from those for saline solution. CLINICAL RELEVANCE: Bethanechol and erythromycin significantly increased solid-phase GE in healthy horses and may have value for use as prokinetic agents in certain gastrointestinal tract diseases.     

Gastric emptying 16 to 26 years after treatment of infantile hypertrophic pyloric stenosis

Long-term follow-up was performed 16 to 26 years after conservative (group I, n = 18) and operative (group II, n = 38) treatment of 56 patients who had infantile hypertrophic pyloric stenosis (IHPS). The study encompassed the scintigraphic determination of gastric emptying rates for solids and liquids, an interview to obtain medical history and ascertain whether a current disorder of the upper gastrointestinal tract was present, and a clinical examination. Gastric emptying rates were measured on two different days for solids and liquids. The standard solid meal consisted of two scrambled eggs, two slices of toast, and 20 g of margarine. The gastric emptying rate for liquids was measured using 300 mL of apple juice. The scrambled eggs and apple juice were each marked with 2.2 MBq technetium 99m-sulphur-colloid. Two control collectives were used in this study; one group (physicians) served to create a reference curve for gastric emptying, and the other group, with the same age and gender distributions as those of the patients, served to evaluate the frequency of gastrointestinal complaints, by means of a questionnaire. There was no significant rate difference for gastric emptying between the patients treated conservatively or surgically and the controls. No association could be construed between the frequency of gastrointestinal symptoms or disorders and the gastric emptying rates for solids and liquids. The results presented here substantiate that clinically relevant disturbances of stomach motility after IHPS appear to be rare.     

Transdermal delivery of erythromycin lactobionate--implications for the therapy of gastroparesis

BACKGROUND: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment. METHODS: Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection. RESULTS: Erythromycin passes across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to approximately equal to 28 cm2 should provide therapeutic levels of drug within 3 h. CONCLUSIONS: Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.     

Lack of pharmacokinetic interaction between tiagabine and erythromycin

This study was conducted to investigate the effects on the pharmacokinetics of tiagabine at steady state when coadministered with therapeutic doses of erythromycin. Tiagabine doses of 4 mg twice daily and erythromycin doses of 500 mg twice daily were administered for 4 days in an open-label, crossover, two-period interaction trial in 13 healthy volunteers. No statistically significant differences in maximum plasma concentration (Cmax), area under the concentration-time curve (AUC tau), or half-life (t1/2) of tiagabine were observed when tiagabine was administered alone or in combination with erythromycin. A statistically significant treatment effect was observed for time to maximum concentration (tmax; 0.72 after tiagabine alone versus 0.56 hours after administration with erythromycin). No statistically significant differences were seen between men and women except in tmax and t1/2; these differences were thought to be of no clinical significance. The decrease in tmax seen in women in this study is interpreted as a differential effect of erythromycin on gastric emptying of females and not as an interaction between tiagabine and erythromycin. No changes in laboratory parameters or vital signs were attributable to trial medication. The most common treatment-emergent adverse events that were possibly related to trial medication were central nervous system effects (e.g., headache, dizziness); all adverse events were transient, the majority were rated mild in severity, and did not require additional action. Coadministration of erythromycin in healthy subjects does not significantly affect the pharmacokinetics of tiagabine at the doses tested.     

Dysfunctional voiding in women: which muscles are responsible?

We studied the effect of mixed agonist-antagonist opioids (nalbuphine and pentazocine) and a kappa opioid agonist (U50488H) on gastric emptying and gastrointestinal transit, and their interactions with morphine in rats. In each group, nalbuphine (0.01-30 mg kg-1), pentazocine (1-30 mg kg-1), U50488H (1-100 mg kg(-1)1) or saline was injected i.p. at 0 min. Another four groups of rats received morphine 13.4 mg kg-1 (ED75) and one of the following substances: saline, nalbuphine, pentazocine or U50488H. In both groups, at 30 min, radiolabelled saline 1 ml was infused into the stomach; at 1 h, gastric emptying and gastrointestinal transit were calculated by measuring the radioactivity in the gastrointestinal tract. Slopes for dose-response curves were determined. Nalbuphine significantly, but only weakly, delayed gastric emptying (P < 0.0005) and gastrointestinal transit (P < 0.01). Pentazocine markedly inhibited both, whereas U50488H did not significantly inhibit either. The slopes of the dose-response curves for nalbuphine, but not for pentazocine, on both gastric emptying and gastrointestinal transit were significantly less steep than those for morphine. Nalbuphine significantly antagonized the inhibitory effect of morphine on gastric emptying (P = 0.005) and gastrointestinal transit (P = 0.02), whereas pentazocine and U50488H did not. Nalbuphine and pentazocine delay gastric emptying and gastrointestinal transit, possibly by different mechanisms.     

Effects of ondansetron on gastrointestinal symptoms in carcinoid syndrome

The effect of short-term treatment with the highly selective serotonin receptor antagonist ondansetron on symptoms and gastric emptying in 11 carcinoid patients was studied. Diarrhoea improved in 6 of 6 patients, nausea in 3 of 4 patients. Flushing was not affected. The rate of gastric emptying increased during ondansetron treatment (P = 0.08). No changes in serotonin in platelets and urinary excretion of 5-hydroxyindoleacetic acid were found. It is concluded that ondansetron can improve gastrointestinal symptoms in carcinoid patients and possibly slows gastric emptying.     

Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms

This study investigated effects of glucagon-like peptide-1(7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractility of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmol/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.     

5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and motilin release induced by erythromycin

In the present study we evaluated the effect of ondansetron (formerly indicated as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor antagonist, on erythromycin-induced gallbladder emptying and motilin release, as well as gallbladder emptying induced by a regular meal in healthy volunteers. Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of 0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume or inhibit gallbladder emptying induced by a regular meal. Ondansetron also inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA). These results suggest that serotoninergic mechanisms modulate the effects of erythromycin on the gastrointestinal tract. The exact site of action of ondansetron remains to be identified.     

Cephalosporin-probenecid drug interactions

The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support.     

Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers

BACKGROUND: ABT-229 is a recently developed derivative of erythromycin, devoid of antibiotic activity. We studied the effect of ABT-229 on gastric emptying and postprandial antroduodenal motility in healthy volunteers. METHODS: Placebo, 4 and 16 mg ABT-229 were given as a single oral dose to nine healthy volunteers, in a randomized, 3-period crossover design. A solid meal (250 kcal) was given twice, 45 min after drug ingestion and 4 h later. Gastric emptying of each meal was studied using the 13C-octanoic breath test. Antroduodenal motility was recorded during the total 9-h period. RESULTS: After the first meal, both the 4 and 16 mg doses increased the gastric emptying rate to a similar extent. ABT-229 stimulated the contractile motility of the antrum dose-dependently. The half-emptying time and the lag-phase of gastric emptying correlated with the number of pressure waves that were propagated over the antrum and the mean amplitude of antral pressure waves. After the second meal no significant effects of ABT-229 were found. CONCLUSIONS: A single dose of the new motilin agonist ABT-229 strongly increases the gastric emptying rate in healthy volunteers by increasing the strength and length of propagation of antral pressure waves. ABT-229 has the potential to become a new prokinetic drug.     

Physiologically relevant one-compartment pharmacokinetic models for skin. 2. Comparison of models when combined with a systemic pharmacokinetic model

The discovery of a second isoform of cyclooxygenase (cyclooxygenase-2) that is expressed in inflammatory cells and the central nervous system, but not in the gastric mucosa, offers the possibility of developing anti-inflammatory and analgesic agents that lack the gastrointestinal side effects of currently available nonsteroidal anti-inflammatory drugs. Lead compounds from several different structural classes have been identified and shown to be slow, tight-binding inhibitors that express their selectivity for cyclooxygenase-2 in the time-dependent step. The determination of structures of enzyme-inhibitor co-crystals along with site-directed mutagenesis experiments reveal the molecular basis for selectivity of some, but not all, inhibitors. Preclinical and clinical studies suggest cyclooxygenase-2 inhibitors are highly promising new agents for the treatment of pain and inflammation, and for the prevention of cancer.     

Determination of third-generation cephalosporins by high-performance liquid chromatography in connection with pharmacokinetic studies

The third-generation cephalosporins are semisynthetic beta-lactam antibiotics, including several oral and parental agents with extended activity against Gram-negative pathogens. They are generally determined either by microbiological techniques or by high-performance liquid chromatography (HPLC). The major drawback or bioassays is the lack of specificity, especially when a biotransformation of the cephalosporin molecule leads to active metabolites, or when the antibacterial therapy is based on association with drugs. Thus, for many years, numerous reversed-phase HPLC procedures have been proposed to overcome these difficulties. This review presents different HPLC methods proposed for the quantification in biological fluids of fourteen third-generation cephalosporins, ranged between parenteral and oral compounds. The sensitivity and specificity of these chromatographic procedures are discussed with regard to the pharmacokinetic properties of the antibiotics studied.     

Mouse thyroglobulin: conservation of sequence homology in C-terminal immunogenic regions of thyroglobulin

Gastrin-releasing peptide (GRP) has a wide range of biological actions, including stimulation of the frequency of antral contractions and delaying gastric emptying. The present study was designed to evaluate the role of GRP in the control of gastric emptying of liquid test meals in the rat. The emptying of methyl cellulose given by gavage to fasted rats, or of saline given via the fistula to conscious gastric fistula rats was not influenced by the GRP antagonists, NC-8-89 (Leu13-psi-(CH2NH)-Leu14-bombesin) and 2258U89 ((de-NH2)Phe19, D-Ala24, D-Pro26 psi (CH2NH)Phe27(-GRP (19-27)), at 2 mg/kg, s.c. However, both antagonists (0.02, 0.2 and 2 mg/kg) reversed the inhibitory effect of HCI on gastric emptying in gastric fistula rats (P < 0.05-0.001). When peptone was administered after a preload, but not otherwise, the inhibition of emptying was also partly reversed by both antagonists at all doses used (P < 0.05-0.001). Interestingly, the delay in the emptying of hyperosmolal saline compared to saline, was enhanced at a dose of 0.2 mg/kg of both antagonists (P < 0.05 and P < 0.01). Food intake did not change significantly with the two lower doses of antagonists, but was decreased by the highest dose of NC 8-89. We conclude that GRP specifically inhibits gastric emptying of acid and peptone solutions in the conscious rat.     

Current antimicrobial drugs

In the past few years several new antibiotics became available, but no major inventions as to new treatment strategies were made. There are a few new broad-spectrum antibiotics for the intravenous route like piperacillin-tazobactam, the carbapenem meropenem and the fourth-generation cephalosporins. cefepime and cefpirome. New oral antibiotics include the third-generation cephalosporins ceftibuten, cefetamet and cefpodoxime and the macrolides clarithromycin and azithromycin. The last two have the great advantage of less frequent dosing and fewer side effects than erythromycin. Of the two new quinolones, sparfloxacin and trovafloxacin, trovafloxacin is the more promising. In the treatment of Gram-positive infections the glycopeptide teicoplanin became available and the combined derivatives quinupristin-dalfopristin may prove valuable in the future.     

Comparison of left anterior oblique, anterior, and geometric mean methods in gastric emptying assessment of postpancreaticoduodenectomy patients

Although left anterior oblique (LAO) gastric emptying studies appear to be an adequate alternative to geometric mean (GM) measurements in patients with normal gastric anatomy, it is not clear whether they can be used after gastric or duodenal surgery. In this study, dual-phase gastric emptying studies with combined solid-liquid meal were performed in 54 patients who had undergone pancreaticoduodenectomy (Whipple procedure). Gastric emptying was studied with GM, LAO, and anterior (ANT) methods. T1/2 and percent gastric retention at 10, 30, 60, 90, and 120 minutes were calculated. Results from the three methods were compared using correlation analysis and the t test. The t test showed no significant difference in T1/2 and percent retention values between the GM and LAO or ANT views. The solid emptying T1/2 showed a better correlation between GM and LAO values (r = 0.824) than between GM and ANT (r = 0.589). For the liquid T1/2, the reverse was true. Correlation between GM and ANT (r = 0.939) was better than between GM and LAO (r = 0.839); however, both LAO and ANT views correlated well with GM liquid emptying. It is concluded that the LAO view can replace GM gastric emptying methods in postpancreaticoduodenectomy patients for evaluation of both solid and liquid emptying, although the ANT view appears completely adequate for the study of liquid emptying.     

Relationships between gastric emptying, intragastric meal distribution and blood glucose concentrations in diabetes mellitus

The aim of this study was to evaluate the prevalence of disordered intragastric meal distribution and the relationships between gastric emptying, intragastric distribution, glycemic control and gastrointestinal symptoms in diabetes mellitus. METHODS: Eighty-six patients with diabetes mellitus had measurements of gastric emptying and intragastric distribution of a radioisotopically labeled solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma glucose concentrations), upper gastrointestinal symptoms (questionnaire) and autonomic nerve function (cardiovascular reflexes). Results were compared to those obtained in 20 normal volunteers. RESULTS: Solid and liquid gastric emptying were delayed in the diabetic patients and correlated weakly. Intragastric meal distribution was also often abnormal, with increased retention of both solid and liquid in the proximal stomach and increased retention of solid but not liquid in the distal stomach. In all patients with increased retention of solid in the proximal stomach, emptying from the total stomach was delayed. Gastric emptying of liquid was slower in those subjects who had a mean plasma glucose > 15 mmol/liter during the gastric emptying measurement, when compared to the remainder of the group. CONCLUSION: In patients with diabetes mellitus, there is poor relationship between solid and liquid gastric emptying and intragastric meal distribution is frequently abnormal. Interpretation of the results of gastric emptying measurements should consider meal composition and plasma glucose concentrations.