Mutations in the SMAD4/DPC4 gene in juvenile polyposis.

Familial juvenile polyposis is an autosomal dominant disease characterized by a predisposition to hamartomatous polyps and gastrointestinal cancer. Here it is shown that a subset of juvenile polyposis families carry germ line mutations in the gene SMAD4 (also known as DPC4), located on chromosome 18q21.1, that encodes a critical cytoplasmic mediator in the transforming growth factor-beta signaling pathway. The mutant SMAD4 proteins are predicted to be truncated at the carboxyl-terminus and lack sequences required for normal function. These results confirm an important role for SMAD4 in the development of gastrointestinal tumors.

Oral rehydration for viral gastroenteritis in adults: a randomized, controlled trial of 3 solutions.

BACKGROUND: Pedialyte and Gatorade are advocated for the treatment of dehydration in viral gastroenteritis, but there is limited evidence to support their use. We examine the efficacy, safety, and palatability of Pedialyte, Gatorade, and a New Oral Rehydration Solution (N-ORS). This was a randomized double-blind trial conducted in an inpatient, community hospital. Seventy-five consecutive adult patients (male, 42; female, 33) admitted with viral gastroenteritis were randomized to receive Gatorade, Pedialyte, or N-ORS for 48 hours. A yogurt/rice diet was allowed ad libitum. Stool and urine output, electrolytes, fluid intake, body weight, hematocrit, and palatability of solutions were measured. RESULTS: Sixty completed the study. Stool frequency, consistency, and body weight improved (p < .001) in all 3 groups, but there was no difference between groups. Likewise, urine output, hematocrit, and correlations between fluid ingested, stool weight, or urine output were similar. At admission and 24 and 48 hours later, hypokalemia was observed in 7, 10, and 8 patients with Gatorade; 3, 2, and 1 with N-ORS; and 2, 2, and 1 with Pedialyte, respectively. Similarly, hyponatremia was observed in 6, 9, and 3 patients with Gatorade; 5, 3, and 4 with N-ORS; and 4, 5, and 4 with Pedialyte. Tastewise, Gatorade and N-ORS were rated higher (p < .05) than Pedialyte. Limitations were a smaller sample size and higher dropout (20%). CONCLUSIONS: Gatorade and N-ORS seem to be as effective as Pedialyte in correcting dehydration and in improving bowel symptoms. All 3 solutions were safe. Unlike other groups, hypokalemia persisted in the Gatorade group. Gatorade and N-ORS may be effective in the treatment of dehydration associated with mild viral gastroenteritis.

Cephalosporin-associated colitis and Clostridium difficile.

A case of cephalosporin-associated colitis occurred in which a tissue-cultured morphologic-altering activity was demonstrated in the patient's feces during the active episode. Neutralization of the tissue culture activity by antiserum directed against a partially purified toxin of Clostridium difficile provided a more suggestive link between the colitis and this clostridial species.

Effect of sulfasalazine on digoxin bioavailability.

Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA.

Irradiation increases superoxide dismutase in rat intestinal smooth muscle.

We investigated whether X-irradiation could induce the enzyme superoxide dismutase (SOD) in intestinal muscle. Groups of rats received abdominal irradiation and the time course and dose response for SOD activity determined. Jejunal smooth muscle homogenates were analyzed for the activities of copper/zinc (CuZn) and manganese (Mn) SOD activity and for a mitochondrial marker enzyme, citrate synthase. A progressive rise in Mn SOD activity occurred at 20, 46, and 72 h after 1500 R. No significant changes in Cu-Zn SOD activity occurred at any time after 1500 R. At 20 h after 250 R of X-irradiation, Mn SOD activity increased but no further increase occurred at higher irradiation exposures. At the same time, CuZn SOD activity at 20 h after irradiation was greater than controls only at an exposure of 1000 R (p less than 0.05). Using Western blotting, we were able to clearly demonstrate an increase in immunoreactive Mn SOD protein in muscle samples 20 h after 1500 R. The rise in Mn SOD is not simply due to increase in mitochondrial numbers or increase in all mitochondrial enzyme activities because activity of the mitochondrial marker enzyme citrate synthase was decreased after X-irradiation. Transmission electron microscopic studies demonstrated damage to mitochondria after a dose of 3000 R. The data yield evidence that free radicals play a role in irradiation-induced intestinal smooth muscle injury.

The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation.

In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications.

Calcium supplements and colorectal adenomas. Polyp Prevention Study Group.

Experimental and observational findings suggest that calcium intake may protect against colorectal neoplasia. To investigate this hypothesis, we conducted a randomized, double-blind trial of colorectal adenoma recurrence. Nine hundred thirty patients with a recent history of colorectal adenomas were randomly given calcium carbonate (3 gm daily; 1200 mg elemental calcium) or placebo, with follow-up colonoscopies one and four years after the qualifying examination. The main analysis focused on new adenomas found after the first follow-up endoscopy, up to (and including) the second follow-up examination. Risk ratios of at least one recurrent adenoma and ratios of the average numbers of adenomas were calculated as measures of calcium effect. There was a lower risk of recurrent adenomas in subjects assigned calcium. Eight hundred thirty-two patients had two follow-up examinations and were included in the main analysis; the adjusted risk ratio of one or more adenomas was 0.81 (95% CI 0.67 to 0.99); the adjusted ratio of the average numbers of adenomas was 0.76 (95% CI 0.60 to 0.96). Among subjects who had at least one follow-up colonoscopy, the adjusted risk ratio of one or more recurrent adenomas was 0.85 (95% CI 0.74 to 0.98). The effect of calcium seemed independent of initial dietary fat and calcium intake. No toxicity was associated with supplementation. These findings indicate that calcium supplementation has a modest protective effect against colorectal adenomas, precursors of most colorectal cancers.

Electrohydraulic shock wave lithotripsy (ESWL) fragmentation of retained common duct stones.

Retained or recurrent stones in the common bile duct remain a clinical problem in 2% to 5% of patients undergoing cholecystectomy. Nonoperative extraction via the T tube tract or endoscopic sphincterotomy is successful in 85% to 95% of patients; however, the remainder require reoperation. This study evaluates the efficacy of electrohydraulic shock wave lithotripsy therapy of common duct stones too large to be extracted endoscopically or by T tube. Six patients were entered into the study. Ages ranged from 62 to 93 years. All patients either had severe preexisting systemic disorders or were of an advanced age. Stones ranged in size from 10 to 41 mm, with a mean largest dimension of 22 mm. In all patients either extraction by traditional nonoperative means failed or there was a stone that was considered to be too large to be extracted successfully. Patients were treated with 1200 to 2400 shocks at 16 to 20 kV. Five of six patients were treated with local anesthesia and sedation. Stones were successfully fragmented in all but one patient. Five patients required extraction of the remaining fragments either through the T tube tract (one patient) or via endoscopic sphincterotomy. All patients were free of stones at discharge, with the exception of one patient with severe cirrhosis who had an intrahepatic stone behind a right hepatic duct stricture. This stone had been successfully fragmented but an endoscopic retrograde cholangio-pancreatogram revealed some residual fragments despite normal alkaline phosphatase and bilirubin values. There were no hospital deaths, although the patient with the intrahepatic stone died of bleeding varices several months later. Electrohydraulic shock wave lithotripsy seems to be an effective adjuvant treatment in clearing the bile duct of stones that would otherwise require reoperation.

Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa.

One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock-wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner.

Direct genetic testing for Smad4 mutations in patients at risk for juvenile polyposis.

BACKGROUND: The identification of germline mutations in juvenile polyposis (JP) families has made presymptomatic genetic testing possible. In this study we report the results of genetic testing in two large JP families and develop an algorithm for the clinical management of these patients. METHODS: DNA was extracted from 55 members of 2 JP kindreds, and the Smad4 mutations in the germline were determined by direct sequencing. All family members were then tested for mutations with use of single-strand conformational polymorphism analysis and were invited for genetic counseling. RESULTS: All 18 affected members of both kindreds had a 4-bp deletion in exon 9 of the Smad4 gene. In 30 patients at risk for JP, 17 had previously had negative endoscopic screening results and 13 had never been screened. Five patients at risk had inherited germline Smad4 mutations. Two carriers have had hematochezia but have not been screened, whereas 3 were asymptomatic. The mean age of carriers was 29.8 years (range 9.1-49.5 years), whereas that of noncarriers was 41.0 years (range 8.1-76.5 years). CONCLUSIONS: Compliance has been a problem with endoscopic screening for JP. With genetic testing non-carriers may no longer require frequent screening endoscopy, whereas gene carriers can be targeted for close endoscopic surveillance and early intervention to prevent the development of gastrointestinal cancers. Direct genetic testing significantly improves the presymptomatic diagnosis of gene carriers in JP families with Smad4 mutations.

Effect of beverage osmolality on intestinal fluid absorption during exercise.

To determine how osmolality of an orally ingested fluid-replacement beverage would alter intestinal fluid absorption from the duodenum and/or jejunum during 85 min of cycle exercise (63.3 +/- 0.9% peak O2 uptake) in a cool environment (22 degreesC), seven subjects (5 men, 2 women, peak O2 uptake = 54.5 +/- 3.8 ml . kg-1 . min-1) participated in four experiments separated by 1 wk in which they ingested a water placebo (WP) or one of three 6% carbohydrate (CHO) beverages formulated to give mean osmolalities of 197, 295, or 414 mosmol/kgH2O. CHO solutions also contained 17-18 meq Na+ and 3.2 meq K+. Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested a total of 23 ml/kg body mass of the test solution, 20% (370 +/- 9 ml) of this volume 5 min before exercise and 10% (185 +/- 4 ml) every 10 min thereafter. By using the rate of gastric emptying as the rate of intestinal perfusion (G. P. Lambert, R. T. Chang, D. Joensen, X. Shi, R. W. Summers, H. P. Schedl, and C. V. Gisolfi. Int. J. Sports Med. 17: 48-55, 1996), intestinal absorption was determined by segmental perfusion from the duodenum (0-25 cm) and jejunum (25-50 cm). There were no differences (P > 0.05) in gastric emptying (mean 18.1 +/- 1.3 ml/min) or total fluid absorption (802 +/- 109, 650 +/- 52, 674 +/- 62, and 633 +/- 74 ml . 50 cm-1 . h-1 for WP, hypo-, iso-, and hypertonic solutions, respectively) among beverages; but WP was absorbed faster (P < 0.05) from the duodenum than in the jejunum. Of the total volume of fluid ingested, 82 +/- 14, 74 +/- 6, 76 +/- 5, and 68 +/- 7% were absorbed for WP, hypo-, iso-, and hypertonic beverages, respectively. There were no differences in urine production or percent change in plasma volume among solutions. We conclude that total fluid absorption of 6% CHO-electrolyte beverages from the duodenojejunum during exercise, within the osmotic range studied, is not different from WP.

Intestinal water absorption from select carbohydrate solutions in humans.

Eight men positioned a triple-lumen tube in the duodenojejunum. By use of segmental perfusion, 2, 4, 6, or 8% solutions of glucose (111-444 mM), sucrose (55-233 mM), a maltodextrin [17-67 mM, avg. chain length = 7 glucose units (7G)], or a corn syrup solid [40-160 mM, avg. chain length = 3 glucose units (3G)] were perfused at 15 ml/min for 70 min after a 30-min equilibration period. All solutions were made isotonic with NaCl, except 6 and 8% glucose solutions, which were hypertonic. An isotonic NaCl solution was perfused as control. Water absorption (range: 9-15 ml.h-1.cm-1) did not differ for the 2, 4, and 6% CHO solutions but was greater (P < 0.05) than absorption from control (3.0 +/- 2.2 ml.h-1.cm-1). The 8% glucose and 3G solutions reduced (P < 0.05) net water flux compared with their 2, 4, and 6% solutions, but 8% sucrose and 8% 7G solutions promoted water absorption equivalent to lower CHO concentrations. Water absorption was independent of [Na+] in the original solution. In the test segment, 1) Na+ flux correlated with net water flux (r = 0.72, P < 0.01), K+ (r = 0.78, P < 0.01), and [Na+] (r = 0.68, P < 0.001); 2) Na+ absorption occurred at luminal [Na+] as low as 50 mM; 3) glucose transport increased linearly over the luminal concentration range of 40-180 mM; and 4) net water flux was similar over a range of glucose-to-Na+ concentration ratios of 0.4:1 to 3.5:1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cycle exercise on intestinal absorption in humans.

Intestinal absorption was measured in six trained male cyclists during rest, exercise, and recovery periods with the segmental perfusion technique. Each subject passed a multilumen tube into the duodenojejunum. The experiments consisted of 1) a sequence of 1-h bouts of cycling exercise at 30, 50, and 70% maximal O2 uptake (Vo2max) separated by 1-h rest periods or 2) a 90-min bout at 70% VO2max. The cycling was performed on a constant-load Velodyne trainer. Absorption of water and a 6% carbohydrate-electrolyte (2% glucose, 6% sucrose, 20 meq Na+, 2.6 meq K+) solution (both perfused at 15 ml/min) were compared. The effects of perfusing an isotonic electrolyte solution during mild (30% VO2max) exercise were also studied. Fluid was sampled every 10 min from ports 10 and 50 cm distal to the infusion site. Water flux was determined by differences in polyethylene glycol concentration across the 40-cm test segment. Results showed 1) no difference in water or electrolyte absorption rates among rest, exercise, and recovery periods; 2) no difference in absorption rates among the three exercise intensities or different exercise durations; and 3) significantly greater fluid absorption rates from the carbohydrate-electrolyte (CE) solution than from water. Water flux during rest, exercise, and recovery was about sixfold greater from the CE solution than from the isotonic solution without carbohydrate. We conclude that 1) exercise has no effect on water or solute absorption in the duodenojejunum, 2) fluid absorption occurs significantly faster from a CE solution than from water, and 3) fluid absorption is increased sixfold by addition of carbohydrate to an electrolyte solution.

Absorption from different intestinal segments during exercise.

This study evaluated intestinal absorption from the first 75 cm of the proximal small intestine during 85 min of cycle exercise [63.6 +/- 0.7% peak O2 consumption (VO2 peak)] while subjects ingested either an isotonic carbohydrate-electrolyte beverage (CHO-E) or a water placebo (WP). The CHO-E beverage contained 117 mM (4%) sucrose, 111 mM (2%) glucose, 18 meq Na+, and 3 meq K+. The two experiments were performed a week apart by seven subjects (6 men and 1 woman; mean VO2 peak = 53.5 +/- 6.5 ml . kg-1 . min-1). Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested 23 ml/kg body weight of the test solution, 20% (383 +/- 11 ml) of this volume 5 min before exercise and 10% (191 +/- 5 ml) every 10 min thereafter. By using the rate of gastric emptying (18.1 +/- 1.1 vs. 19.2 +/- 0. 7 ml/min for WP and CHO-E, respectively) as the rate of intestinal perfusion, intestinal absorption was determined by segmental perfusion from the duodenum (0-25 cm) and jejunum (25-50 and 50-75 cm). Water flux was different (P < 0.05) between solutions in the 0- to 25- and 25- to 50-cm segments for WP vs. CHO-E (30.7 +/- 2.7 vs. 15.0 +/- 2.9 and 3.8 +/- 1.1 vs. 11.9 +/- 3.3 ml . cm-1 . h-1, respectively). Furthermore, water flux differed (P < 0.05) for WP in a comparison of the 0- to 25- to the 25- to 50-cm segment. Total solute flux (TSF) was not significantly different among segments for a given solution or between solutions for a given segment. There was no difference between trials for percent change in plasma volume. These results indicate that 1) fluid absorption in the proximal small intestine depends on the segment studied and 2) solution composition can significantly effect water absorption rate in different intestinal segments.

Effects of solution osmolality on absorption of select fluid replacement solutions in human duodenojejunum.

These experiments examined relationships between initial osmolality and carbohydrate (CHO) composition of an infused solution and osmolality and water and CHO absorption in a test segment. A triple-lumen tube with a 10-cm mixing segment and a 40-cm test segment was passed into the duodenojejunum. The infusion port was approximately 10 cm beyond the pyloric sphincter. Perfusion solutions were hypotonic (186 mosmol/kg; solution A), isotonic (283 mosmol/kg; solution B), and hypertonic (403 mosmol/kg; solution C). All solutions contained 18 meq Na+ and 3 meq K+. In the mixing segment, osmolality increased 83 mosmol/kg and decreased 90 mosmol/kg for solutions A and C, respectively. Corresponding changes in the test segment were an increase of 60 mosmol/kg and a decrease of 34 mosmol/kg. The osmolality of solution B did not change. In the test segment, mean osmolality and water and total solute fluxes were not significantly different among solutions, but solution C produced 27% greater fluid absorption than did solution A. When net fluid movement from mixing and test segments was determined, solution A produced 17% greater fluid absorption than did solution C. The mean increases in plasma and urine volumes over the 80-min test period were not significantly different. In the test segment, water flux correlated with CHO and Na+ fluxes but not with osmolality. In conclusion, 1) significant differences in solution osmolality were eliminated within the proximal duodenum and 2) perfusing 6% CHO solutions with osmolalities ranging from 186 to 403 mosmol/kg did not produce significant differences in fluid homeostasis (plasma volume) at the end of an 80-min test period.

Effect of hypohydration on gastric emptying and intestinal absorption during exercise.

Dehydration and hyperthermia may impair gastric emptying (GE) during exercise; the effect of these alterations on intestinal water flux (WF) is unknown. Thus the purpose of this study was to determine the effect of hypohydration ( approximately 2.7% body weight) on GE and WF of a water placebo (WP) during cycling exercise (85 min, 65% maximal oxygen uptake) in a cool environment (22 degrees C) and to also compare GE and WF of three carbohydrate-electrolyte solutions (CES) while the subjects were hypohydrated. GE and WF were determined simultaneously by a nasogastric tube placed in the gastric antrum and via a multilumen tube that spanned the duodenum and the first 25 cm of jejunum. Hypohydration was attained 12-16 h before experiments by low-intensity exercise in a hot (45 degrees C), humid (relative humidity 50%) environment. Seven healthy subjects (age 26.7 +/- 1.7 yr, maximal oxygen uptake 55.9 +/- 8.2 ml . kg-1 . min-1) ingested either WP or a 6% (330 mosmol), 8% (400 mosmol), or a 9% (590 mosmol) CES the morning following hypohydration. For comparison, subjects ingested WP after a euhydration protocol. Solutions ( approximately 2.0 liters total) were ingested as a large bolus (4.6 ml/kg body wt) 5 min before exercise and as small serial feedings (2.3 ml/kg body wt) every 10 min of exercise. Average GE rates were not different among conditions (P > 0.05). Mean (+/-SE) values for WF were also similar (P > 0.05) for the euhydration (15.3 +/- 1.7 ml . cm-1 . h-1) and hypohydration (18.3 +/- 2.6 ml . cm-1 . h-1) experiments. During exercise after hypohydration, water absorption was greater (P < 0.05) with ingestion of WP (18.3 +/- 2. 6) and the 6% CES (16.5 +/- 3.7), compared with the 8% CES (6.9 +/- 1.5) and the 9% CES (1.8 +/- 1.7). Mean values for final core temperature (38.6 +/- 0.1 degrees C), heart rate (152 +/- 1 beats/min), and change in plasma volume (-5.7 +/- 0.7%) were similar among experimental trials. We conclude that 1) hypohydration to approximately 3% body weight does not impair GE or fluid absorption during moderate exercise when ingesting WP, and 2) hyperosmolality (>400 mosmol) reduced WF in the proximal intestine.

Excitatory amino acid regulation of the enkephalin phenotype in mouse embryonic spinal cord cultures.

Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10(-7)-10(-3) M) of N-methyl-D-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5-phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 microM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 microM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration-dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 microM) and quisqualate (10 microM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co-treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX-induced down-regulation of mRNAppENK. Our results indicate that the activity-dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor.

Long-term cimetidine and anticholinergic therapy in patients with gastrinoma.

Two patients with gastrinomas were treated with cimetidine and an anticholinergic drug for greater than 20 months after exploratory laparotomy disclosed no solitary resectable tumor. Both have done well, and thus this therapy is recommended as a safe and effective alternative to total gastrectomy in reliable patients. Additional therapeutic methods are needed to control tumor growth.

Severe abdominal vasculitis with hepatitis B antigenemia.

Two cases of necrotizing abdominal vasculitis associated with hepatitis B are reported. The diagnosis of mesenteric vasculitis is often delayed, and intestinal perforation is common. Early recognition of the disease and early treatment with corticosteroid and immunosuppressive drugs may alter the course of the disease. Preoperative diagnosis is best made by mesenteric arteriography and rectal biopsy.

Intestinal fluid absorption during exercise: role of sport drink osmolality and [Na+].

The purpose of this study was to evaluate the effects of modifying the osmolality and [Na+] of orally ingested rehydration beverages during exercise on intestinal absorption in the duodenum and upper jejunum. Six subjects randomly ingested (23 mL.kg-1 BW) the following 6% carbohydrate solutions with and without Na+ during 85-min of cycle exercise (65% VO2 peak) in a cool (22 degrees C, 40% RH) environment: a) 0 Na+, 245 mOsm.kg-1; b) 20 mEq Na+, 283 mOsm.kg-1; c) 20 mEq Na+, 169 mOsm.kg-1; d) 50 mEq Na+, 275 mOsm.kg-1; and e) 50 mEq Na+, 176 mOsm.kg-1. To alter solution osmolality and maintain carbohydrate concentration constant, glucose, sucrose, fructose, and maltodextrin were used in different combinations. Nasogastric and multilumen tubes were fluoroscopically placed in the stomach and intestine, respectively, to simultaneously determine gastric emptying and intestinal absorption as previously described (Lambert et al., Int. J. Sports Med.17:48, 1996). Gastric emptying was not different among solutions and averaged 13 +/- 0.5 mL.min-1. Net fluid absorption was not different among beverages nor between duodenum and jejunum (x = 10.8 +/- 1.6 and 7.9 +/- 1.1 mL.cm-1.h-1, respectively). Mean osmolality increased significantly (P < 0.05) from the duodenum to the jejunum (242 +/- 6 and 293 +/- 7 mOsm.kg-1, respectively) but did not differ among solutions. These data provide evidence that a hypotonic 6% carbohydrate beverage with 50 mEq.L-1 Na+ did not enhance intestinal fluid absorption or attenuate the decline in plasma volume during exercise more than an isotonic carbohydrate-electrolyte solution or a hypotonic carbohydrate solution without sodium.