Double-blind placebo-controlled multicentre studies of rebamipide, a gastroprotective drug, in the treatment of functional dyspepsia with or without Helicobacter pylori infection.

BACKGROUND: Functional dyspepsia is a problem that is difficult to treat in clinical practice. AIM: To evaluate the efficacy and safety of rebamipide (a cytoprotective drug) in functional dyspepsia. METHODS: Patients with functional dyspepsia (n=557) were divided a priori into two studies by Helicobacter pylori status, and enrolled in a 2-week baseline evaluation period. Ninety-nine patients with Helicobacter pylori and 173 patients without Helicobacter pylori, continuing to have at least moderate upper abdominal pain or discomfort, were randomly assigned to rebamipide 100 mg, rebamipide 200 mg or placebo, three times a day, in a double-blind design for 8 weeks. RESULTS: There was significant improvement of individual symptom scores from baseline in all the treatment arms. No significant improvement of individual symptom scores was observed in either rebamipide group at the end of the studies compared to placebo, although the belching score was significantly reduced in the rebamipide 100 mg and 200 mg groups at week 2 (P=0.017 and P=0.012, respectively) in the Helicobacter pylori-positive patients. The ratio of patients who requested usage of the study medication again was greater in the rebamipide 100 mg (85%) and 200 mg (96%, P=0.020) groups compared with the placebo group (72%) among Helicobacter pylori-positive patients. There were no serious study medication related adverse events. CONCLUSIONS: Rebamipide was not superior to placebo in terms of individual symptoms at the end of treatment.

Antibiotic prophylaxis in percutaneous endoscopic gastrostomy.

OBJECTIVES: The benefit of antibiotic prophylaxis in percutaneous endoscopic gastrostomy is controversial. The aim of this study is to determine whether prophylactic antibiotic treatment with Cefazolin reduces the incidence of peristomal infection after percutaneous endoscopic gastrostomy. METHODS: Of the 131 hospitalized or nursing home patients referred for percutaneous endoscopic gastrostomy, 115 were enrolled in a prospective randomized double-blind placebo controlled trial. Sixty-one (group 1) were randomized in a double-blind fashion and received either Cefazolin or saline pregastrostomy. Fifty-four patients (group 2) were on antibiotics for prior medical indications pregastrostomy. Patients had their peristomal area evaluated on a daily basis for 1 wk after gastrostomy. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0 to 3; a maximum score of 8 or higher or the presence of pus was criteria for infection. RESULTS: Wound infection occurred in 4 of 30 (13%) participants receiving Cefazolin and in 6 of 31 (19%) participants receiving saline (p > 0.5). In the 54 patients on antibiotics for prior indications, wound infection was observed in 2 subjects (3%). This finding was a significant difference when compared with the placebo group (p < 0.02). CONCLUSIONS: A single dose of Cefazolin prophylaxis does not reduce the overall peristomal wound infection in percutaneous endoscopic gastrostomy. Patients receiving prior extended antibiotic therapy have fewer peristomal wound infections.

Insulin-like growth factor I in human gastrointestinal exocrine secretions.

Insulin-like growth factor I (IGF-I) is the mediator of growth hormone dependent growth. The peptide has been identified by radioimmunoassay in a number of human exocrine secretions of the gastrointestinal tract including (nM): saliva 0.9, gastric juice 3.5, jejunal chyme 24.6, pancreatic juice 3.6, and bile 0.9. The identification of IGF-I in pancreatic juice was confirmed by HPLC. The intravenous injection of 1 unit/kg secretin increased pancreatic juice IGF-I content from a basal level of roughly 4 nM to nearly 20 nM. Conversely, the IGF-I content of bile was unaffected by secretin. Radioligand blot analysis of samples of gastric juice, jejunal chyme and pancreatic juice demonstrated that these fluids contained no IGF binding proteins. Thus, unlike IGF-I in serum, IGF-I secreted into the gastrointestinal lumen is not bound to insulin-like growth factor I binding proteins. Since the growth factor is not protein bound, its concentration in the gut lumen may be high enough to exert biological activity.

Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12)

OBJECTIVE: To evaluate protein-bound cyanocobalamin (vitamin B12) absorption before and after omeprazole (Prilosec) therapy in healthy male volunteers. DESIGN: Clinical trial in which each volunteer served as his own control. SETTING: Outpatient department of a university medical center. PARTICIPANTS: Ten healthy, male volunteers 22 to 50 years old. INTERVENTION: Each participant had a modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as well as measurements of serum vitamin B12, gastrin, and folate levels. Five patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole daily. After 2 weeks of omeprazole therapy, these tests were repeated. MEASUREMENTS: The modified Schilling test, gastric analysis, serum gastrin level, folate level, and cyanocobalamin level. RESULTS: At the end of the 2-week treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P = 0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40 mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P < 0.05). CONCLUSIONS: Omeprazole therapy acutely decreased cyanocobalamin absorption in a dose-dependent manner.

Aspirating gastric residuals causes occlusion of small-bore feeding tubes.

A frequent mechanical problem encountered with small-bore feeding tubes is lumenal obstruction of the tube. A number of studies have described methods to prevent tube occlusion and restore patency once the tube becomes occluded. It has been observed that most intact protein formulas will clot when acidified to a pH of less than 5.0. This study evaluated the question of whether gastric feeding tubes occlude more frequently when they are used for checking gastric residuals by aspirating acidic gastric juices into the tube than when gastric residuals are not checked. Patients who were fed intragastrically via a small-bore feeding tube with intact protein formulas were divided into two groups. Gastric residuals were checked in group A patients every 4 hours, whereas no residuals were checked in group B patients. Fifteen patients in group A were followed for a total of 138 patient days and 13 patients in group B were followed for 154 patient days. Ten occlusive episodes occurred in the group A patients, whereas only one occlusive episode occurred in the group B patients. This difference was statistically significant (p = .0171). We concluded that small-bore feeding tubes occlude more frequently when used to aspirate gastric residuals.

Large-bore feeding tube occlusion by yeast colonies.

This is a first report of three patients with silicone feeding tubes (two with percutaneous endoscopic gastrostomies and one with a jejunostomy, all 20 French catheters) that have formed a thick yeast crust on the inner luminal surface causing tube occlusion in two cases. Candida species were isolated in all three tubes. The yeast crust could not be removed with a brush or with fungicidal drugs such as nystatin and amphotericin B. Histologic sections through these feeding tubes revealed yeast penetration through the silicone material, explaining the adherent nature of the crust. This complication may also explain the observed material deterioration with subsequent breakage.

Ornithine decarboxylase activity during gastric ulcer healing in dogs.

Ornithine decarboxylase (ODC) activity has been associated with mucosal growth and injury, yet, little information is available on ODC activity during gastric ulcer healing. We measured ODC activity in the ulcer base submucosa and the surrounding mucosa at 1 cm and 2 cm and assessed ulcer surface healing and a histologic score in experimentally induced ulcers (Quinton ulcer-maker) at 0 and 5 hr and at one, two, three, four, and seven days. A total of 26 dogs were studied, eight of which received 2% difluoromethylornithine (DFMO, a specific inhibitor of ODC) in drinking water. Ulcer healing was assessed by digitizing initial (plug size), and final ulcer surface area and was expressed as percent ulcer surface reduction. A histologic score was assessed by two independent pathologists unaware of the treatment. ODC induction was observed in the submucosa of the ulcer base but not in the surrounding mucosa. The baseline submucosal ODC activity was measured at 0.2 +/- 0.1 pmol (14CO2)/mg protein/hr, and at one day the ODC activity increased to 4.0 +/- 0.7, at three days to 15.2 +/- 5.5, and at seven days to 2.6 +/- 1.0 (P less than 0.001). DFMO treatment delayed GU healing significantly up to three days, but no difference was noted at seven days. The assessed histologic parameters did not correlate with ODC activity, and DFMO treatment did not alter the histologic score. These data suggest that polyamine biosynthesis occurs in the ulcer base submucosa during the first seven days of experimentally placed gastric ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional status and dietary intake of children with sickle cell anemia.

The nutritional status and dietary intake of children with sickle cell anemia were examined to confirm the presence of deficiencies. Nine children with sickle cell anemia and 19 controls were assessed. Resting energy expenditure was measured with open circuit indirect calorimetry and body composition was estimated from skinfold measurements. Three-day food records were analyzed for protein, zinc, vitamin A, folic acid, and iron content. Serum vitamin A, red blood cell zinc, red blood cell folate, serum folate, serum ferritin, hematocrit, total urine nitrogen, and 24-h urine creatinine levels were measured. The children with sickle cell anemia were leaner, weighed less, and had lower red blood cell zinc levels, lower serum vitamin A levels, lower urine nitrogen levels, and greater resting energy expenditure than controls. Serum and red blood cell folate levels were within normal ranges and similar to controls. The serum ferritin level was higher than controls and higher than normal for age. Dietary intake of energy and protein was more than that of controls, and dietary intake of zinc, vitamin A, folic acid, and iron was similar to that of controls and adequate compared to the Recommended Dietary Allowances. Further studies are needed to explain the physical and biochemical differences seen in children with sickle cell anemia despite dietary intakes that appear to be adequate and similar to those of controls.

Cimetidine in the treatment of acetaminophen overdose.

Acetaminophen overdose is generally treated with oral N-acetylcysteine. While N-acetylcysteine is protective, an additional effective mode of treatment is desirable in large overdoses. A growing body of evidence suggests that cimetidine significantly reduces the hepatotoxicity of an acetaminophen overdose and that its hepatoprotective action may be additive to that of N-acetylcysteine. We report a case of acetaminophen overdose treated with oral N-acetylcysteine in conjunction with cimetidine by continuous i.v. infusion. The 4-h acetaminophen level was 410 micrograms/ml, and the highest measured level of serum glutamic oxaloacetic transaminase was 83 IU/L on day 3, indicating minimal hepatic toxicity.

Availability of insulin from total parenteral nutrition solutions.

Insulin is frequently required in total parenteral nutrition (TPN) solutions to control hyperglycemia. The purpose of this study was to evaluate the recovery of human insulin from standard TPN solutions with and without lipids and from TPN solutions with specialized amino acid formulations and to compare it to the insulin recovery from normal saline. All solutions were mixed in currently utilized PVC-free bags (ethylene vinyl acetate) and drained through PVC-containing tubing. Human insulin (Humulin-R) was spiked with 125I-labeled insulin and then added in concentrations of 10, 25, and 50 units to 1-liter bags containing 39-g amino acids (10% Freamine-III; or 6.9% Freamine HBC; or 8% Hepatamine), 257-g dextrose, electrolytes (Hyperlyte-R), 1000 units of heparin, MVI-12, and MTE-5 Concentrate. Alternate sets of bags contained 125 ml of 20% Intralipid and an appropriate amount of sterile water to keep the final volume at 1 liter. Actual clinical conditions of preparation, storage, and administration were simulated in this in vitro experiment. Multiple samples were collected during the 8-hr infusion period directly in gamma counter vials. All experiments and assays were done in triplicate. Our findings indicate that human insulin availability in TPN solutions is much higher (90%-95%) than the 50% suggested in the literature. Insulin recovery was not appreciably altered by adding lipids or by using Freamine HBC. Insulin recovery from TPN solutions was significantly reduced if they contained Hepatamine (87% and 88%, p less than 0.05) as compared to Freamine (90% and 94%).(ABSTRACT TRUNCATED AT 250 WORDS)

Unclogging feeding tubes with pancreatic enzyme.

Occlusion of small-bore feeding tubes (Dobbhoff, 8 French) was observed at our institution in 32 of 90 patients (35%) over an 8-month period. The purpose of this study was to evaluate possible causes of tube occlusion and to assess the efficacy of an activated pancreatic enzyme solution to clear obstructed feeding tubes. A Drum cartridge catheter was inserted into the occluded feeding tube to displace any liquid formula and to apply the enzyme solution close to the obstruction site. Water was injected first and served as control. The feeding tubes of 32 patients occluded 60 times during an 8-month period and declogging was attempted in 44 instances. Water was able to clear the obstruction in 12 cases. In the remaining 32 cases, the activated pancreatic enzyme was injected, and the obstruction was cleared in 23 cases (72%). The causes of failure to clear the obstruction were determined in seven cases: tablet impaction (three cases), knotted feeding tube (two cases), tomato seed occluded the feeding port (one case), formula clot in two-third length of the tube for 24-hr (one case). Thus, the pancreatic enzyme solution was successful in restoring tube patency in 23 of 24 instances (96%) where formula clotting was the likely cause of occlusion and Coke or water had failed.

Reversible cardiomyopathy due to selenium deficiency.

Selenium is an essential trace element and a component of glutathione peroxidase, an enzyme that may help to prevent oxidative damage to cells. Selenium deficiency has been linked to the development of Keshan disease, a dilated congestive cardiomyopathy occurring primarily in children living in rural China. Sporadic cases have been reported in the United States in individuals with poor nutritional intake, mostly in individuals on long-term home parenteral nutrition. This report describes a young black woman with Crohn's disease in whom a congestive cardiomyopathy developed and was subsequently reversed following administration of selenium.

Absence of luminal intrinsic factor after gastric bypass surgery for morbid obesity.

Abnormally low serum cobalamin levels (less than 180 pg/ml) have been observed in 154 of 429 patients (36%) at an average of 22 months (range 3-64 months) after gastric bypass surgery for morbid obesity. Twenty-four patients underwent a Schilling test and retrograde endoscopy of the bypassed gastric segment to determine the presence of intrinsic factor (IF) in gastric aspirates and in mucosal biopsies at 22 +/- 4 months after surgery. Five patients had a normal cobalamin level (405 +/- 44 pg/ml), and gastric juice intrinsic factor was present in three of them (11 +/- 7 ng/ml). Nineteen patients had a low cobalamin level (113 +/- 8 pg/ml), and gastric juice IF was found in only two subjects of this group (10 ng/ml each). Basal gastric juice IF concentration of healthy control subjects was 24 +/- 5 ng/ml. Schilling test results were normal in all five patients of the first group and in only nine patients of the group with cobalamin deficiency after surgery. To assess whether IF was present within the parietal cells of subjects with absent luminal IF, we studied gastric biopsy material of 14 patients using a well-characterized indirect immunoperoxidase method. IF was identified in fundic mucosal biopsy specimens of all 14 patients with absent gastric juice IF. We conclude that cobalamin deficiency occurs in a significant number of patients after gastric bypass and is associated with absence of gastric juice IF. We propose that this abnormality might be caused by inadequate secretion of IF from the bypassed stomach.

Gastric ulcer healing after laser treatment in dogs.

Endoscopic laser photocoagulation of ulcers is increasingly used to produce hemostasis in patients who are actively bleeding or in patients with stigmata of recent hemorrhage. Little information is available describing ulcer healing rates after laser treatments. The aim of this study was to compare the healing rates of gastric ulcers treated with laser energy (Nd:YAG) with untreated ulcers in dogs. Two standard gastric ulcers (12-14 mm diameter) were created in each dog stomach using an ulcer maker (Quinton) under endoscopic guidance and one was randomly selected for laser treatment (L), while the other served as control (C). Ten laser spots were applied circumferentially around the ulcer crater with a mean energy of 595 J per ulcer. Ten dogs were studied; four of which were sacrificed after one week and six after two weeks. Healing of treated ulcers was compared with that of control ulcers and expressed as a percentage of the initial ulcer surface. Histologic injury and reepithelialization were scored by two pathologists unaware of the treatment. Laser-treated ulcers healed significantly slower than untreated ulcers at one week (53% L vs 94% C, P less than 0.05) and histologic injury was greater in ulcers treated with laser photocoagulation. At two weeks, only 82% of the laser-treated ulcer surface was healed in comparison with 94% (P less than 0.05) healing in untreated ulcers, although the mean histologic injury score was not different at two weeks. Reepithelialization was decreased both at one week (11% L vs 71% C, P less than 0.01) and at two weeks (75% L vs 100% C, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clearing obstructed feeding tubes.

This is a report of an in vitro study evaluating the ability of six solutions to dissolve clotted enteral feeding, which can cause feeding tube occlusion. The following clotted enteral feeding products were tested: Ensure Plus, Ensure Plus with added protein (Promod 20 g/liter), Osmolite, Enrich, and Pulmocare. Clot dissolution was then tested by adding Adolf's Meat Tenderizer, Viokase, Sprite, Pepsi, Coke, or Mountain Dew. Distilled water served as control. Dissolution score for each mixture was assessed blindly. Best dissolution was observed with Viokase in pH 7.9 solution (p less than 0.01). Similar results were obtained when feeding tube patency was restored in eight in vitro occluded feeding tubes (Dobbhoff, French size 8) by using first Pepsi (two/eight successful) and then Viokase in pH 7.9 (six/six successful). We also report our experience in the first 10 patients with occluded feeding tubes using this Viokase solution injected through a Drum catheter into the feeding tube. In seven patients, this method proved to be successful, and the reasons for failure in three patients include a knotted tube, impacted tablet powder, and a formula clot fo 24 hr duration and 45 cm in length.

Gastrointestinal angiodysplasia in renal failure.

We identified angiodysplasia as a cause of gastrointestinal bleeding in 15 of 47 patients (32%) with chronic renal failure (CRF) treated with dialysis who were evaluated for upper or lower gastrointestinal hemorrhage during a 5-year period. Nine patients had lesions in the upper, four in the lower, and two in the upper and lower gastrointestinal tract. Ten patients with angiodysplasia experienced more than one bleeding episode during that time. Active hemorrhage from a vascular lesion was seen in nine patients (60%). Erosive gastritis and/or duodenitis was the second most common finding. These data confirm how frequent a cause of recurrent bleeding angiodysplasia is in patients with CRF undergoing dialysis.

Clogging of feeding tubes.

This is a report of an in vitro study evaluating clotting ability of some formulas with intact protein and hydrolyzed protein sources in a series of buffers ranging from a pH of 1 thru 10. The following 10 products were tested: Ensure Plus, Ensure, Enrich, Osmolite, Pulmocare, Citrotein, Resource, Vivonex TEN, Vital, and Hepatic Acid II. Protein (10 and 20 g/liter) was added to Citrotein and Ensure Plus. All formulas were tested at full and some at half strength. Clotting occurred only in premixed intact protein formulas (Pulmocare, Ensure Plus, Osmolite, Enrich, Ensure) and in Resource. No clotting was observed for Citrotein (intact protein formula in powder form), Vital, Vivonex TEN, and Hepatic Aid II. Adding protein did not cause or increase clotting. In summary, clotting of some liquid formula diet appears to be an important factor causing possible gastric feeding tube occlusion. The following measures may help in preventing this problem: flushing before and after aspirating for gastric residuals to eliminate acid precipitation of formula in the feeding tube, advance the nasogastric feeding tube into the duodenum if possible, and avoid mixing these products with liquid medications having a pH value of 5.0 or less.