Effect of a synthetic prostaglandin E1 derivative, misoprostol, on fasted gallbladder volume and on meal-induced gallbladder emptying in man

The effect of a single oral dose of 400 micrograms of misoprostol versus placebo on the fasted gallbladder volume and on meal-induced gallbladder emptying was assessed in 10 healthy subjects according to a double-blind study protocol. Gallbladder volumes were measured by means of real-time ultrasonography. The fasted gallbladder volume before drug administration was 18.9 +/- 1.1 cm3 on the placebo day, and 18.8 +/- 1.4 cm3 on the misoprostol day. No significant change in the gallbladder volume was observed 30 minutes after drug administration (18.3 +/- 1.3 cm3 placebo vs 20.2 +/- 1.8 cm3 misoprostol). The gallbladder volume 10 min after the test meal was significantly larger after misoprostol (16.9 +/- 1.7 cm3) than after placebo (12.8 +/- 1.6 cm3), p less than 0.02. However, the differences at subsequent time points (i.e. 20, 30, and 40 min after the test meal) proved to be insignificant. An insignificant effect of misoprostol on gallbladder emptying was revealed also by the analysis of the respective gallbladder ejection fractions. We conclude that misoprostol does not have any significant effect on fasted gallbladder volume or on meal-induced gallbladder emptying in humans.     

Effect of calcitonin on gastric emptying and on postprandial gastrin and insulin release in patients with type I gastric ulcer

In a double-blind placebo-controlled study, the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in six patients with type I gastric ulcer. Synthetic salmon calcitonin 415 pmol i.v. was given as a bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin suppressed gastric emptying in all patients examined. The mean gastric transit time, MTT90, increased from 38.1 +/- 0.4 min after placebo to 43.1 +/- 0.6 min after calcitonin (P less than 0.001). Calcitonin significantly blunted the postprandial gastrin release: AUC0-90 10,398 +/- 2886 ng. l-1 min (placebo) and 8238 +/- 2573 ng. l-1 min (calcitonin), P less than 0.05, and abolished the postprandial insulin release--AUC0-90 2244 +/- 230 mU.l-1 min (placebo) vs. 638 +/- 198 mU.l-1 min (calcitonin), P less than 0.01. A steady increase in the serum glucose during calcitonin infusion, reaching up to 5.6 +/- 0.31 mmol.l-1 at the end of the infusion, was observed. Calcitonin did not significantly affect serum calcium or phosphorus concentrations. The authors conclude that a delayed gastric emptying is to be expected in patients undergoing calcitonin treatment.     

Effect of calcitonin on gastric emptying and on serum insulin and gastrin concentrations after ingestion of a mixed solid-liquid meal in humans

In a double-blind placebo-controlled study, we examined the effect of calcitonin on gastric emptying, and on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after a mixed solid-liquid meal in 11 healthy men. Synthetic salmon calcitonin was administered as a 415 pmol i.v. bolus injection followed by a 90-min infusion to reach an overall dose of 62.25 pmol/kg body mass. Gastric emptying of a radiolabeled meal was surveyed by means of a gamma camera. A pronounced inhibition of gastric emptying with calcitonin was observed in all subjects (median gastric half emptying time 60.3 min after placebo versus 197.6 min after calcitonin; p less than 0.001). Calcitonin did not effect the postprandial gastrin release, nor did it change significantly the serum calcium or phosphorus concentrations. A decreased postprandial insulin release by calcitonin (mean +/- SEM area under the insulin curve 2,124.6 +/- 382.0 min mU L-1 after placebo versus 640.9 +/- 124.0 min mU L-1 after calcitonin; p less than 0.002) was accompanied by a different pattern of serum glucose concentrations during the infusion of the hormone when compared to the situation with a placebo. We discuss potential mechanisms and clinical relevance of our findings.     

Ultrasonographic study of gall-bladder emptying in obese patients.

In order to assess gall-bladder (GB) motility in obese patients, we measured by ultrasound the GB fasting volume (FV) in 45 women (23 obese, 22 controls) and 43 men (21 obese, 22 controls). The FV was larger in obese women (45.9 +/- 21.6 cm3) than in controls (26.6 +/- 10.7 cm3) (P less than 0.001), and also in obese men (39.2 +/- 20.2 vs. 23.8 +/- 9.9 cm3) (P less than 0.01). In obese women, GB FV correlated with relative body weight. No correlation was found between GB volume and age in obese subjects. In controls, but not in obese subjects, the GB ejection fraction was significantly greater in men (65.3 +/- 19.9%) than in women (51.3 +/- 9.0%) (P less than 0.02). Gall-bladder contraction was not decreased in obese subjects vs. controls, suggesting that GB hypocontractility is not a lithogenic risk factor in obesity. The observation that GB emptying does not correlate with body weight represents another argument that obesity does not impair GB contraction.     

Effect of calcitonin on gastric emptying in patients with an active duodenal ulcer.

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.     

Mitral stenosis: left atrial dynamics reflect altered passive and active emptying

To assess the passive and the active phases of left atrial (LA) emptying, LA volumes and function were studied in 15 patients with mitral stenosis (MS) in sinus rhythm and in 11 normal subjects (NL) with two-dimensional echocardiography with simultaneous electrocardiograms. LA and left ventricular (LV) volumes were measured with the biplane area-length method. LA maximal and minimal volumes were measured at mitral valve opening and closure, respectively. In addition, LA volume was measured at onset of atrial systole (beginning of the P wave on the electrocardiogram). LA volumes were larger in MS compared with NL; Maximal 122 +/- 65 cm3 versus 46 +/- 12 cm3, p less than 0.001; onset of atrial systole 108 +/- 63 cm3 versus 29 +/- 12 cm3, p less than 0.001; minimal 90 +/- 60 cm3 versus 18 +/- 7 cm3, p less than 0.001. LA passive emptying volume (maximal minus volume at onset of atrial systole) was not statistically different in MS compared with NL, while LA active emptying volume (volume at onset of atrial systole minus minimal) was larger in MS compared with NL (17 +/- 5 cm3 versus 11 +/- 5 cm3, p less than 0.05). The net result was normal LA total emptying volume (maximal minus minimal) MS 32 +/- 11 cm3, NL 28 +/- 5 cm3. In contrast, the LA emptying fractions were significantly decreased in MS compared with NL (passive 0.13 +/- 0.08 versus 0.39 +/- 0.1, p less than 0.0001, active 0.19 +/- 0.08 versus 0.38 +/- 0.07, p less than 0.0001, total 0.30 +/- 0.1 versus 0.62 +/- 0.07, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prokinetic effect of alpha-adrenergic antagonist, and beta-adrenergic antagonist on gall-bladder motility in humans with gall-stone disease

INTRODUCTION: The effects of cholinergic agents and vagal control on gall-bladder motility are well defined. Alpha adrenergic antagonists have been found in previous studies to have a prokinetic effect on gall-bladder motility in normal human patients. Their effects have not, however, been fully elucidated in patients with gall-stone disease. OBJECTIVE: Our aim was to determine the effects of alpha-antagonists and beta-antagonists on gall-bladder motility in human patients with gall-stone disease. METHODS: In this single-blind, three-way crossover study, a slow release formulation of 80 mg propranolol (beta-antagonist), and 25 mg indoramin (alpha-antagonist), and placebo were administered separately to 10 patients with gall-stone disease on three separate days 8 h before assessment of gall-bladder volumes by ultrasonography. Gall-bladder volumes were assessed in the fasting state and at 5 min intervals for 50 min after a standard proprietary enteral feed (Ensure 180 ml, Abbott). Differences between the placebo and postadrenergic antagonist scan volumes were tested using the Wilcoxon-signed rank test. RESULTS: There were no significant differences in the mean fasting gall-bladder volumes after receiving propranolol, indoramin and placebo (23.6+/-3.9, 22.3+/-4.3, 26.8+/-7.2 ml, mean+/-SEM, respectively). In the postprandial period, however, indoramin significantly enhanced postprandial gall-bladder emptying compared with placebo between 5 and 30 min (P<0.05) after which refilling commenced. There were no significant postprandial gall-bladder volume differences between propranolol and placebo. CONCLUSION: Indoramin, an alpha-adrenergic antagonist, acts as a prokinetic agent enhancing postprandial gall-bladder emptying in patients with gall-stone disease. This effect is similar to its effect on postprandial gall-bladder emptying in healthy individuals.     

Symptomatic,radionuclide and therapeutic assessment of chronic idiopathic dyspepsia

Twenty-eight patients with chronic idiopathic dyspepsia defined by the presence of chronic unexplained symptoms suggestive of gastric stasis and directly related to food ingestion were included in this prospective study. Gastric emptying of the liquid and solid phases of a meal was quantified by a dual-isotope method, and symptoms were evaluated by a diary and a visual analog scale. Delay in gastric emptying was evidenced in 59% of the dyspeptic patients; it occurred with liquids in more cases than solids. Quantitative and qualitative evaluation of symptoms was of no practical value in predicting the presence of objective stasis. The dyspeptic patients were included in a double-blind randomized controlled trial of cisapride, a new gastrokinetic drug devoid of central antiemetic effects. After six weeks of cisapride treatment, all patients with initially abnormal gastric emptying rates for liquids, and all but one for solids returned to normal ranges, and significant differences between cisapride and placebo groups were observed for half emptying times of both solids (136 +/- 16 min vs 227 +/- 32 min; P less than 0.02) and liquids (61 +/- 4 min vs 132 +/- 37 min; P less than 0.01). Cisapride also significantly improved dyspeptic symptom scores at weeks 3 and 6 of treatment as compared to those measured before treatment. Nevertheless, the decrease in global diary score was significantly higher than that seen with placebo at week 3 (-16 +/- 6 vs -1 +/- 9; P less than 0.05), but not at week 6 (-18 +/- 5 vs -10 +/- 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

A synthetic prostaglandin E2 analogue, enprostil, hastens gastric emptying of solids in patients with an active duodenal ulcer

The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

Colour Doppler-guided spectral analysis of gall-bladder wall flow

For the purpose of the present study to diagnose gall-bladder cancers, which cannot be detected or are only partly visible by conventional ultrasonography (US), we attempted differential diagnoses of 69 patients with gall-bladder diseases (12 with gall-bladder cancer, five with acute cholecystitis, 11 with chronic cholecystitis, 27 with cholesterol polyp and 14 with adenomyomatosis) using the evaluation of gall-bladder wall blood flow (GWBF). GWBF was evaluated by colour Doppler-guided spectral analysis (CDSA). Thirty-three healthy volunteers were selected as controls at random. Two parameters of GWBF, namely flow velocity and resistive index (RI), were compared between patients with gall-bladder diseases and healthy volunteers. GWBF could be ultrasonically evaluated in 92 (90%) of 102 subjects. All 12 patients with gall-bladder cancer had a significantly rapid blood flow value compared with other patients and healthy volunteers. There was no significant difference in RI among patients and healthy volunteers. When cut-off level of the flow velocity was set at 30 cm/s, gall-bladder cancer could be diagnosed by flow velocity with 100% sensitivity (12/12) and 96% specificity (50/52). Using the same cut-off level of the flow velocity, 17 patients were analysed prospectively. In four asymptomatic gall-bladder cancers and two acute cholecystitis cases with some symptoms, the flow velocity was over 30 cm/s. In two of four patients with gall-bladder cancer, only a part of the tumour was visualized on conventional abdominal US. In conclusion, CDSA was more useful for diagnosing gall-bladder lesions than the conventional abdominal US due to estimation of arterial flow velocity in the gall-bladder wall.     

Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man

The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose, vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder vlume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9±2.9 cm³ before and 26.2±3.2 cm³ after the drug receipt (P<0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipineper os without, however, reaching the level of statistical significance. Following 20 mg nifedipineper os, a marked delay in the meal-stimulated gallbladder emptying occurred as reflected by a decrease in the gallbladder ejection fraction from 48.1±4.5% (placebo) to 26.4±5.0% (nifedipine) (P<0.02) at 30 min and from 54.0±3.6% (placebo) to 33.2±4.6% (nifedipine) (P<0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder.     

Effect of calcitonin on gastric emptying

The effect on gastric emptying of synthetic salmon calcitonin administered intravenously (415 pmol bolus injection followed by infusion to reach an overall dose of 62.25 pmol.kg-1 body mass) versus placebo was examined in 13 healthy men. Gastric emptying of a radiolabeled solid meal was assessed with a gamma camera. The gastric emptying course was analyzed with the use of the power-exponential fitting. A marked delay in gastric emptying was observed in all subjects studied: the median gastric half emptying time was 60.3 min after placebo and 196.5 min after calcitonin (p less than 0.001). At the same time, analysis of the parameter S revealed that calcitonin did not elicit any consistent change in the shape of gastric emptying curves.     

Effects of bombesin,calcitonin, and enkephalin on canine jejunal water and electrolyte transport

The aim of this investigation was to study the effects of the peptides bombesin, calcitonin, and enkephalin on net jejunal water and electrolyte fluxes using the triple-lumen gut perfusion technique in conscious dogs. Intestinal transport was measured during intravenous infusions of bombesin (1 microgram/kg/hr, 8 studies), or calcitonin (3 micrograms/kg/hr, 5 studies), or methionine enkephalin (20 micrograms/kg/hr, 6 studies); each dog was used as its own control with infusion of 150 mmol/liter NaCl preceding and succeeding each peptide infusion. Net water absorption was reduced from a control value of 17 +/- 4.18 to 7 +/- 1.79 microliter/cm/min by bombesin (P less than 0.05) and increased from a control value of 15 +/- 3.95 to 29 +/- 5.58 microliters/cm/min by enkephalin (P less than 0.05). Bombesin reduced net sodium and chloride absorption, while enkephalin increased net absorption of sodium and bicarbonate. Calcitonin did not have any detectable effect in the dose used in this study in dogs. We conclude that bombesin and enkephalin can effect the transport of water and electrolytes in the canine jejunum.     

The effect of simvastatin and bezafibrate on bile composition and gall-bladder emptying in female non-insulin-dependent diabetics

Abstract Female non-insulin-dependent diabetics have a high prevalence of gallstones. Treatment of hyperlipidaemia in these patients may modify the risk. Seventeen female non-insulin-dependent diabetics (age 35–65) were treated with simvastatin ( n = 10) or bezafibrate ( n = 7) and had the cholesterol saturation index (CSI) of bile and gall-bladder emptying measured before and after 3 months therapy. In both groups, there was a significant reduction in serum cholesterol following treatment. The mean pretreatment cholesterol saturation indices of bile did not differ between the two groups but, after 3 months therapy, there was a highly significant difference in CSI between the bezafibrate group (2.0 ± 0.33) and the simvastatin group (1.1 ± 0.14) P < 0.002. Whereas the increase in the CSI (42%) observed with bezafibrate therapy was significant, the decrease in the simvastatin group (14%) was only significant in those whose pretreatment cholesterol saturation indices were elevated. Despite the differences in CSI observed between the two treatment groups, no changes in gall-bladder emptying were detected.     

Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis.

BACKGROUND: Erythromycin has recently been found to be a gastrointestinal prokinetic agent in humans. Acute hyperglycaemia has been associated with delayed gastric emptying in both healthy controls and diabetic patients. Our aim was to investigate in gastroparetic patients (diabetics and idiopathics) whether hyperglycaemia, per se, reduces gastric motility during erythromycin-induced acceleration of gastric emptying of solids. METHODS: In 12 gastroparetic patients, 6 diabetics and 6 idiopathics, gastric emptying of solids was measured scintigraphically after giving placebo in normoglycaemia (5-8.9 mmol/l glucose) or 200 mg erythromycin lactobionate intravenously in normo- or hyperglycaemia (16-19 mmol/l glucose) induced by intravenous glucose infusion in random order on separate days. RESULTS: Erythromycin in normoglycaemia accelerated solids gastric emptying compared with placebo in all patients by abolishing the lag-phase duration and by decreasing the retained percentage of a meal in the stomach at 120 and 150 min (14.5% +/- 5.3% versus 88.4% +/- 10.6% and 3.5% +/- 2.1% versus 70.1% +/- 15.4%, respectively) (P < 0.001). The retained isotopic percentage in the stomach after erythromycin in induced hyperglycaemia compared with erythromycin in normoglycaemia, at 120 and 150 min, was increased (51.9% +/- 9.8% versus 14.5% +/- 5.3%, and 24.5% +/- 5.9% versus 3.5% +/- 2.1%, respectively) (P < 0.001) but was decreased in comparison with placebo (P < 0.001). A significantly increased percentage of isotope was retained in the stomach of the diabetic patients at 120 and 150 min, compared with the idiopathics, only after giving erythromycin in the hyperglycaemic condition (57.6% +/- 8.7% versus 46.1% +/- 7.6% (P = 0.036) and 27.8% +/- 5.7% versus 21.1 +/- 4.4% (P = 0.040), respectively). CONCLUSIONS: Hyperglycaemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis and increases the retained isotopic meal in the stomach. Hyperglycaemia reduces gastric motility more in the diabetic patients with gastroparesis than in idiopathic patients.     

Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obestity.

Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown. METHOD: Twenty-six normal-weight volunteers (body mass index [BMI] less than 30) were compared with 14 morbidly obese patients (BMI greater than 40). Gallbladder volumes were measured ultrasonographically, after fasting and following stimulation with intravenous cholecystokinin-octapeptide (CCK-8) RESULTS: Preoperatively, fasting gallbladder volume and residual volume after CCK stimulation were both two times greater in the obese group (P<0.02 versus controls). Per cent gallbladder emptying was not different. Gallbladder refilling was four times higher in the obese patients (P<0.01). By six weeks postoperatively, the obese patients lost 1.4+/-0.1% body weight per week. Gallbladder emptying decreased 18.4% (80.3+/-3.9% to 65.5+/-6.9%; P<0.05); residual volume rose one-third (not significant), and refilling fell 60.5% (0.43+/-0.09 to 0.26+/-0.04 mL/min; P=0.07). Three patients with weight losses of greater than 1.7% per week developed gallstones; gallbladder emptying fell outside the 95 percentile. By six months, weight loss slowed to 0.5+/-0.1% per week; gallbladder motility improved modestly. No further stones developed. CONCLUSION: Rapid weight loss following laparoscopic gastric banding impairs gallbladder emptying and when pronounced, gallstones form by six weeks postoperatively. The accompanying reduction in gallbladder emptying, increased gallbladder residual volume and decreased refilling promote gallbladder stasis and hence stone formation.     

Antidiabetic agent englitazone enhances insulin action in nondiabetic rats without producing hypoglycemia

The new antihyperglycemic agent englitazone (CP-68,722) was examined in nondiabetic rats. Administration of englitazone at 50 mg/kg/d for 8 days did not produce overt hypoglycemia but it lowered basal plasma insulin by 59% and 41% in rats fed ad libitum and fasted overnight on the last day, respectively. Drug treatment also lowered (P less than .05) plasma nonesterified fatty acids (1.09 +/- 0.05 to 0.36 +/- 0.05 mmol/L) and cholesterol (2.41 +/- 0.08 to 2.06 +/- 0.07 mmol/L) in fasted rats, and glycerol (0.25 +/- 0.02 to 0.14 +/- 0.02 mmol/L) in fed rats but had no effect on 3-hydroxybutyrate or lactate levels despite the hypoinsulinemia. Disposition of an oral glucose load (1 g/kg) in drug-treated fed rats was identical to that in control rats despite a 40% reduction in the area under the plasma insulin curve. Insulin-stimulated 2-deoxy-D-3H-glucose uptake was significantly (P less than .05) enhanced in adipocytes prepared from both fasted and fed drug-treated rats (0.56 +/- 0.07 to 0.84 +/- 0.03 and 0.79 +/- 0.02 to 1.00 +/- 0.02 nmol/5 min, respectively, at insulin concentration of 2,500 microU/mL). There was also a significant increase in the basal rate of 2-deoxyglucose uptake (0.07 +/- 0.01 to 0.24 +/- 0.07 nmol/5 min) in adipocytes from fasted rats only. Insulin-stimulated lipogenesis from 3H-2-glucose was enhanced in adipocytes from drug-treated fed rats (7.72 +/- 0.09 to 10.19 +/- 0.10 nmol glucose/45 min at insulin concentration of 2,500 microU/mL) but no effect was observed in adipocytes from fasted rats (2.57 +/- 0.30 to 2.33 +/- 0.16 nmol glucose/45 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylphenidate associated with narcotics for the treatment of cancer pain

Thirty-two patients with chronic pain due to advanced cancer were treated with methylphenidate (10 mg with breakfast and 5 mg with lunch) for 3 days, versus placebo, in a randomized, double-blind, cross-over study designed to evaluate the capacity of methylphenidate to potentiate the analgesic effect of narcotics and/or to decrease sedation induced by narcotics. In 28 evaluable patients, the intensity of pain (visual analogue 0-100) and intake of extra doses of analgesics (number of doses/day) were 43 +/- 27 and 2.2 +/- 2.4 during methylphenidate, versus 55 +/- 24 (P less than 0.02) and 2.9 +/- 2.9 (P less than 0.002) during placebo, respectively. Activity and drowsiness (visual analogue 0-100) were 57 +/- 25 and 58 +/- 24 after methylphenidate, respectively, versus 41 +/- 26 (P less than 0.05) and 45 +/- 27 (P less than 0.02) after placebo. Upon completion of the study, the investigator and the patient chose methylphenidate blindly as a more useful drug in 23 cases (83%) and 20 cases (70%), respectively (P less than 0.02). No cases of severe toxicity were observed. We conclude that methylphenidate can increase the analgesic effect and decrease sedation of narcotics in this population.     

Gastric emptying of liquids and solids in the portal hypertensive rat

The effects of portal hypertension on gastric motor function were investigated using the rat staged portal vein ligation model. Gastric emptying of liquids and solids was studied separately following meals labeled with 51Cr or 99Tc by whole stomach scintillation counting. Portal hypertension was consistently established in experimental rats (splenic pulp pressure: mean +/- SEM, portal hypertension versus control, 16.8 +/- 0.7 vs 11.8 +/- 0.7 mm Hg, P less than 0.0001). Although liquids were emptied in an exponential manner and solids in a linear fashion, gastric emptying of both meals was more rapid in the experimental rats. Ten minutes after the liquid meal, more than 50% of the meal had emptied from the stomachs of portal hypertensive rats while only one third of the meal had cleared in the control group (P less than 0.02). Gastric emptying of the solid meal was significantly accelerated in experimental rats at 60 and 120 min (percent meal remaining: portal hypertension versus control, 41.9 +/- 4.0 vs 55.4 +/- 3.5 and 21.5 +/- 4.9 vs 32.6 +/- 4.3, P less than 0.05). Stomachs of portal hypertensive animals were heavier (P less than 0.009) and histologic examination revealed submucosal edema. Thus, a possible mechanism of the disrupted gastric motor function in portal hypertension is decreased gastric wall compliance secondary to edema.     

Reduced bone mineral content in totally thyroidectomized patients: possible effect of calcitonin deficiency

To further investigate the relationship between calcitonin deficiency and osteoporosis, we have measured bone mineral content (BMC) by single photon absorptiometry in patients made iatrogenically calcitonin deficient by prior total thyroidectomy for thyroid cancer. Compared to sex-, age-, height-, and weight-matched normal controls, male patients had a significantly lower mean BMC at the midradius (1.162 +/- 0.02 vs. 1.301 +/- 0.05 g/cm; P less than 0.02) and the distal radius (1.180 +/- 0.04 vs. 1.338 +/- 0.04 g/cm; P less than 0.01). Female patients also had a significantly lower BMC at the midradius compared to those of a similarly matched group of normal controls and a group of patients on L-T4 suppression for nodular goiters (0.791 +/- 0.04 vs. 0.896 +/- 0.05 vs. 0.891 +/- 0.03 g/cm; P less than 0.025). We conclude that calcitonin deficiency from surgical thyroidectomy is associated with significant decreases in bone mineral content in both sexes. This lends further support to the concept that calcitonin deficiency may be an important causative factor in the development of osteoporosis.