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The metabolic bases for "paradoxical" and normal feeding.

Hexoses infused slowly into the duodenum or hepatic-portal vein reduce feeding. However, hexoses can increase food intake following rapid infusion via either of these two routes. Insulin responses and resultant glycemic changes differ following fast and slow duodenal glucose infusion. This is unlikely to be the primary explanation, because fructose affects feeding but is not a secretagogue of insulin under our testing conditions. In follow-up studies, we infused glucose or fructose into the hepatic-portal vein at the fast or the slow rate, and measured 14C incorporation into liver mitochondria and glycogen, and tritiated water uptake into hepatic lipids. Fast infusion of glucose or fructose increased lipid formation, reducing mitochondrial uptake and glycogen formation, and was associated with hunger enhancement. Slow hexose infusion was associated with substrate uptake into mitochondria and glycogen, with reduced uptake into hepatic fat. These findings all are consistent with the previously observed positive correlation seen between mitochondrial oxidation and satiety (28).

Animals↗

Acute reflux pancreatitis in rats: a comparison between two experimental models.

This study was undertaken in order to compare the reliability of two acute reflux pancreatitis models in rats, one performed by positioning a silicon tube in the duodenum and the other by creating a gastro-jejunal anastomosis. In two groups (A = 10 and B = 10 rats) a silicon tube was positioned in the duodenum; in the remaining two groups (C = 12 and D = 6 rats) a latero-lateral antecolic anisoperistaltic gastro-jejunal anastomosis was performed 30 days before surgery. A closed duodenal loop was created for 12 hours in groups A and C but not in B and D. Rats in both groups A and C developed acute pancreatic inflammation of a mild degree. Sham operated rats with silicon tube placement had higher histological damage scores than those with gastro-jejunal anastomosis. The difference found between the two groups of rats which underwent gastro-jejunal anastomosis was more marked than that between the two groups which had silicon tube placement. It was concluded that the creation of a gastro-jejunal anastomosis is probably the safer procedure to allow gastro-intestinal flow in acute reflux pancreatitis in rats.

Amylases↗

Immediate postoperative feeding in urological surgery.

The value of immediate postoperative enteral hyperalimentation with an elemental diet (high nitrogen Vivonex, full strength) at 125 cc per hour for 4 days was assessed in patients after radical urological surgery. Of 32 patients studied 21 received an elemental diet using a Vivonex Moss tube, which is a 3-lumen tube with esophagogastric decompression and simultaneous duodenal feeding, and the remaining 11 had a nasogastric tube only without nutritional support. We have used a selected group of parameters, including serum albumin, serum transferrin, creatinine height index, weight loss, total lymphocyte count, nitrogen balance and plasma fibronectin. All patients in the Moss tube group approached or achieved positive nitrogen balance by 4 days postoperatively, whereas the nasogastric tube group remained in negative nitrogen balance. Postoperative paralytic ileus was prevented in the majority of patients in the Moss tube group while receiving full nutritional support. We have found that the use of the Moss tube is a reasonable approach for postoperative alimentation. The tube is relatively easy to insert and well tolerated, and its use is a less expensive alternative to parenteral hyperalimentation.

Enteral Nutrition↗

Management of swallowing disorders and chronic aspiration by glottic closure procedure.

We report an 18-year-old man with a posterior fossa tumor who had to undergo a partial resection of the tumor and supportive radiation therapy. Functional deficits of the lower cranial nerves, particularly the glossopharyngeal and vagal nerves, associated with severe swallowing disorders and refractory aspiration pneumonia were seen postoperatively. The admission to the intensive care unit (ICU) resulted from increasing respiratory failure accompanied by recurrent septic episodes. Nutritional support via nasogastric tube and later percutaneous endoscopic gastrostomy (PEG) were hampered by complications such as persistent sinusitis, local dermatitis surrounding the entrance of the PEG tube, and the development of duodenal ulcers. Furthermore, the use of continuous subglottic aspiration failed to prevent pulmonary infections. After a 9-week stay in the ICU due to inadequate antimicrobial therapy of aspiration pneumonia and the patient's persistent sepsis, a temporary surgical separation of airway and food passages was performed by glottic closure. Subsequently chronic aspiration stopped, and 3 months after admission to the ICU, the patient had stable vital organ function and was transferred to a surgical ward free of infections. Glottic closure was reversed successfully 7 months later. When compared with laryngeal function on admission, there was no more impairment. Thus, temporary glottic closure seems to be an efficacious treatment to prevent life-threatening septic complications in patients with refractory aspiration pneumonia.

Adolescent↗

Effect of gastric and transpyloric tubes on gastric emptying and duodenogastric reflux.

The effect of thin and pliable gastric and transpyloric duodenal tubes on gastric emptying was studied in healthy volunteers. Gastric emptying was unaffected by both gastric and transpyloric tubes. Gastric emptying was also similar whether a milk-cream meal was instilled via a tube or was swallowed. The effect of a transpyloric tube on postprandial and fasting duodenogastric reflux was studied by using a technique that does not require a transpyloric tube in order to measure reflux. Duodenogastric reflux was similar in the fasting state and after feeding and was not affected by a transpyloric tube. In conclusion, thin and pliable gastric and transpyloric tubes do not affect gastric emptying and duodenogastric reflux in humans, and, in addition, the mode of administration of a meal does not affect gastric emptying.

Duodenum↗

Balloon catheter sphincteroplasty and biliary stone expulsion into the duodenum in patients with an indwelling T tube.

BACKGROUND: To present an alternate approach for treating residual biliary stones in patients with indwelling T tube that uses the immature tract created by the T tube to carry out both sphincteroplasty and expulsion of the calculi with the same angioplasty balloon catheter. METHODS: This technique was performed in five patients. Access to the bile duct was through an 8-Fr T tube. First a guidewire was inserted and advanced beyond the obstructing stone to the duodenal lumen. The T tube was removed over the guidewire, and a balloon catheter was introduced. Sphincteroplasty was carried out. Then the balloon was deflated and retracted to a position proximal to the stone. It was then reinflated and used to push the stone, expelling it into the duodenum. RESULTS: In all cases, all biliary stones were expelled without pain, in a single session, and with no immediate complications. All patients showed rapid clinical and analytic improvement. During clinical and echographic follow-up of 2-22 months (mean = 12.4 months), there were no complications or relapses. CONCLUSIONS: Our limited experience indicates that sphincteroplasty and expulsion of biliary stones with angioplasty balloon catheters through the T tube immature tract is a simple, safe, low-cost technique that gives good results.

Aged↗

Canine exocrine pancreatic secretory changes induced by an intragastric ethanol test meal.

In five dogs with chronic gastric fistulas (Thomas cannula) and a new type of chronic pancreatic fistula which permits collection of pure nonactivated pancreatic juice after ingestion of a test meal, the following series of experiments were performed: In the first series, a test meal (400 gm. canned dog meat) was given with 200 ml. saline simultaneously infused through the gastric cannula. In response to this stimulus, the 20-minute peak pancreatic flow rate and bicarbonate output were respectively 33% and 34%, of the maximal secretion of the pancreatic gland obtained with secretin in six control dogs provided with gastric and the classical Thomas duodenal fistula. The 20-minute peak protein output represented 84% of the maximal secretory capacity attained with dose-response curves to CCK in the same group of control animals. In the second series either 1.5 or 2.0 gm./kg. ethanol were given instead of saline. Intragastric ethanol induced a dissociation of pancreatic secretion: a significant inhibition of flow rate, of bicarbonate concentration and output and a significant rise of protein concentration; protein output remaining unchanged. It is postulated that ethanol, acting on the stomach and duodenojejunum, evokes, independently of its gastrin-releasing capacity, and unknown humoral or nervous mechanism that counteracts the ethanol-elicited cholinergic-mediated inhibition of pancreatic protein secretion which has been previously described.

Animals↗

Endogenous CCK inhibits colonic contractions in unrestrained conscious rats.

As cholecystokinin octapeptide (CCK-OP) and feeding have been reported to relax the circular muscle contractions of the proximal colon in unrestrained conscious rats under fasting conditions, the, action of cholecystokinin, released after duodenal infusion of a low residual diet of clinimeal, was studied on the motor activity of the proximal colon in unrestrained conscious rats. We used an implantable telemetry system with a miniature strain gauge force transducer introduced into the rat proximal colon. By using a specific radioimmunoassay system for CCK, plasma levels of CCK before and after duodenal infusion of clinimeal (0.5, 1.0, 2.0 ml) were determined at 0, 5, 10, 20, 30, 60 min in the portal blood. The clinimeal infusion caused a significant increase in CCK levels of the portal plasma during 5 and 30 min. This increase was in a dose-dependent manner. In accordance with this increase in plasma CCK, the motor activity of the proximal circular muscle was suppressed significantly. A bolus injection of the CCK A receptor antagonist, loxiglumide, CR 1505 (0.1, 0.5 and 1.0 mg/kg ip), prior to clinimeal blocked the inhibitory action of CCK on the motor activity in a concentration-dependent manner. These data suggest that endogenous CCK released by a residual diet is involved in the mechanism of inhibition of motor activity in the proximal colon.

Animal Feed↗

Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies.

PURPOSE: This study was conducted to compare the luminal composition of the upper gastrointestinal tract in the fasted and fed states in humans, with a view toward designing in vitro studies to explain/predict food effects on dosage form performance. METHODS: Twenty healthy human subjects received 250 mL water or 500 mL Ensure plus (a complete nutrient drink) through a nasogastric tube and samples were aspirated from the gastric antrum or duodenum for a period up to 3.5 h, depending on location/fluid combination. Samples were analyzed for polyethylene glycol, pH, buffer capacity, osmolality, surface tension, pepsin, total carbohydrates, total protein content, and bile salts. RESULTS: Following Ensure plus administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L-1 DeltapH-1 (vs. 7-18 mmol L-1 DeltapH-1), contents were hyperosmolar, gastric pepsin levels doubled, and surface tension was 30% lower than after administration of water. Post- and preprandial duodenal pH values were initially similar, but slowly decreased to 5.2 postprandially, whereas buffer capacity increased from 5.6 mmol L-1 DeltapH-1 (fasted) to 18-30 mmol L-1 DeltapH-1 (p<0.05). Postprandial surface tension in the duodenum decreased by >30%, bile salt levels were two to four times higher, luminal contents were hyperosmotic, and the presence of peptides and sugars was confirmed. CONCLUSIONS: This work shows that, in addition to already well characterized parameters (e.g., pH, and bile salt levels), significant differences in buffer capacity, surface tension, osmolality, and food components are observed pre-/postprandially. These differences should be reflected in test media to predict food effects on intralumenal performance of dosage forms.

Adult↗

Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans.

We have carried out simultaneous, quantitative measurements of absolute gallbladder (GB) storage and emptying in 6 subjects with gallstones, using a modified duodenal perfusion technique that incorporates technetium 99m-labeled diethyl phenylcarbamomethyl iminodiacetate (99mTc-HIDA) as a GB bile marker in addition to indocyanine green as a hepatic bile marker. The technique was validated by measuring duodenal recovery of 99mTc-HIDA (mean +/- SEM, 101% +/- 4%), and also by studying 2 subjects who had undergone cholecystectomy. During the first hour following an evening meal, cumulative GB ejection of 99mTc-HIDA in the 6 subjects with gallstones was 43% +/- 12%. This was accompanied by GB storage of most hepatic indocyanine green (70% +/- 5%) during each 10-min interval of that hour. During subsequent overnight fasting, storage of hepatic indocyanine green (89% +/- 2%) was accompanied by ejection of 99mTc-HIDA from the GB in 33 of the 66 hourly intervals. Since 'simultaneous' filling and emptying cannot occur through the cystic duct, the results suggest frequent alternations in absolute GB storage and emptying, a phenomenon more analogous to a bellows than to the conventional concept of a simple pump.

Aged↗

Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin.

The purpose of this work was to develop a novel mucoadhesive DL-lactide/glycolide copolymer (PLGA) nanosphere system to improve peptide absorption and prolong the physiological activity following oral administration. The desired PLGA nanospheres with elcatonin were prepared by the emulsion solvent diffusion method to coat the surface of the resultant nanospheres with a mucoadhesive polymer such as chitosan, poly(acrylic acid), and sodium alginate. Their mucoadhesive properties were evaluated by measuring the nanospheres adsorbed to a rat everted intestinal sac (in vitro). The chitosan-coated nanospheres showed higher mucoadhesion to the everted intestinal tract in saline than the other polymer-coated nanospheres. There was no mucoadhesion site-specificity of the chitosan-coated nanospheres between duodenal, jejunal, and ileal sacs. The payload of drug in the chitosan-coated nanospheres was successfully increased by using the solvent diffusion method in oil. The pattern of drug release of the resultant nanospheres did not differ markedly from that of uncoated nanospheres. The chitosan-coated nanospheres with elcatonin were administered intragastrically to fasted Wistar rats. The chitosan-coated nanosphere reduced significantly the blood calcium level compared with elcatonin solution and uncoated nanospheres, and the reduced calcium level was sustained for a period of 48 hr. Even under nonfasting conditions, the mucoadhesion of chitosan-coated nanospheres was unaltered and the reduction in blood Ca levels was maintained satisfactorily.

Acrylic Resins↗

Exocrine pancreatic secretion and plasma levels of cholecystokinin, pancreatic polypeptide, and somatostatin after single and combined intraduodenal application of different bile salts in man.

Bile salts are intraduodenal stimulants of basal pancreatic secretion. This study aims to show whether the three main bile salts of human bile differ in their action on pancreatic secretion, and whether they enhance or inhibit each other after combined use. Furthermore, the effect on gastroenteropancreatic peptide release is evaluated. Twelve subjects were provided with a gastroduodenal double-lumen tube. Equimolar doses (0.6 mmol) of taurocholate (322 mg), taurodeoxycholate (313 mg), and a combination of both stimuli were given intraduodenally. Another 12 subjects received taurochenodeoxycholate (313 mg) instead of taurocholate. Volume, bicarbonate, trypsin, and lipase were determined in duodenal aspirates. Cholecystokinin, pancreatic polypeptide, and somatostatin were measured radioimmunologically in plasma samples. All bile salts and combinations exerted a significant hydrokinetic and ecbolic effect. The hydrokinetic response of the combined stimuli was significantly higher as compared with taurocholate and taurochenodeoxycholate, respectively. As far as concerns the ecbolic response, the difference was significant only for trypsin output as compared with taurochenodeoxycholate. Plasma cholecystokinin rose significantly only after the combined stimuli. Pancreatic polypeptide and somatostatin increased significantly after all stimuli, except pancreatic polypeptide after taurocholate. Combined use enhances the hydrokinetic and ecbolic effects of single bile salts. Cholecystokinin may, hereby, be involved as a mediator of the ecbolic effect. Pancreatic polypeptide release indicates cholinergic mechanisms as further mediators. As demonstrated by somatostatin release, counter-regulatory mechanisms are also triggered by intraduodenal bile salts.

Bile Acids and Salts↗

Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration.

Clozapine, a lipophilic effective atypical antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Clozapine solid lipid nanoparticles have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and stearylamine as a positive charge inducer by hot homogenization followed by ultrasonication method. Particle size and charge measurements were made with Malvern Zetasizer. Pharmacokinetics of clozapine incorporated in solid lipid nanoparticles (SLNs), after intravenous (i.v.) administration to conscious male Wistar rats were studied. The aim of this research was to find out whether the bioavailability of clozapine can be improved by administering clozapine SLN duodenally to rats. Tissue distribution studies of clozapine SLN and suspension were carried out in Swiss albino mice. Average size and zeta potential of SLNs of different lipids with stearylamine ranged from 96.7+/-3.8 to 163.3+/-0.7 nm and 21.3+/-1.3 to 33.2+/-0.6 mV, respectively. AUC((0-infinity)) was increased (up to 2.91-fold) and clearance was decreased (up to 2.93-fold) when clozapine entrapped in SLNs with stearylamine were administered intravenously. Bioavailability of clozapine SLNs were 2.45- to 4.51-fold after intraduodenal administration compared with that of clozapine suspension. In tested organs, the AUC and MRT of clozapine SLNs were higher than those of clozapine suspension especially in brain and reticuloendothelial cell-containing organs. These results indicate that SLN are suitable drug delivery system for the improvement of bioavailability of lipophilic drugs such as clozapine.

Animals↗

Duodenal perforation caused by a transpyloric tube in a critically ill infant.

OBJECTIVE: We describe the case of a 2-mo-old infant who weighed 3.5 kg, had alveolar interstitial pneumopathy on mechanical ventilation, and developed a duodenal perforation due to a 6-Fr polyurethane transpyloric tube. METHODS AND RESULTS: Abdominal ultrasound showed the tube to be within the intestinal lumen. Due to this diagnostic error, nutrition was administered through the tube and the patient developed severe peritonitis. Laparotomy showed a perforation due to the transpyloric tube at the level of the union of the second and third portions of the duodenum. The perforation was sutured but the patient developed new intestinal perforations with severe progressive intestinal damage, leading to multiorgan failure and death. CONCLUSIONS: If there is a clinical suspicion of intestinal perforation secondary to insertion of a transpyloric tube, the position of the tube must be confirmed by radiographic and echographic techniques. In case of doubt, the tube should be withdrawn and endoscopic or contrast radiographic evaluation must be performed.

Critical Illness↗

Gastric tone variations during gastric infusion of fiber-supplemented formulas.

BACKGROUND AND AIM: Despite gastric feeding being a common method of artificial nutritional support, little is known about the effects of enteral nutrition on fundic motor function. The objective of this study was to assess variations of fundic tone and their relation to antroduodenal motility before, during and after nasogastric feeding supplemented or not with fibers. METHOD: Double-blinded studies were performed in random order with the three different diets (2100 kJ) in eight volunteers: fiber free (FF), insoluble fiber (IF) or mixed fiber (MF). Fundic tone was recorded by barostat concomitantly with antroduodenal manometry. RESULTS: Before the infusion, seven spontaneous fundic relaxations occurred during the 24 studies. Concomitantly or less than 2 min before these relaxations, phase III of the migrating motor complex (MMC) with a duodenal onset was recorded. Only the 17 studies without spontaneous fundic relaxation (4 FF, 6 MF, 7 IF) were suitable for the assessment of fundic response to infusion. Disappearance of the volume waves at the beginning and during the whole infusion was observed in 11/17 studies (FF 50%, MF 66% and IF 71%, NS), but a proximal gastric relaxation following the beginning of the infusion occurred in only three individuals, one with the FF and two with IF. When it occurred, fundic relaxation was observed within 2 min and was not different from those observed spontaneously. CONCLUSION: Gastric infusion of a polymeric diet, supplemented or not with fiber, did not promote fundic relaxation in most of the cases but often induced a disappearance of gastric volume waves.

Adult↗

A randomized crossover study of secretin-stimulated endoscopic and dreiling tube pancreatic function test methods in healthy subjects.

OBJECTIVES: We have developed an endoscopic method of secretin endoscopic pancreatic function testing (ePFT) to simplify duodenal fluid collection. Validation of the ePFT requires a direct comparison to the traditional PFT using a Dreiling tube (DT). Our aim was to compare bicarbonate concentrations [HCO3-] obtained by the ePFT and DT methods in healthy subjects (HS). METHODS: HS were randomized to either DT or ePFT, then crossed over to the other test after a minimum 1-wk washout. An age/weight-based sedation bolus was used for each test. DT protocol: Endoscopic placement of a DT was confirmed by fluoroscopy. After a baseline 15-min collection and administration of IV synthetic secretin, fluid was continuously collected in 15-min aliquots for an hour. ePFT protocol: Endoscopy was performed using a 6-mm endoscope. After gastric aspiration and discard and IV secretin, duodenal aspirates were obtained every 15-min for an hour. Fluid specimens were auto-analyzed for [HCO3-]. RESULTS: Twelve HS were enrolled (6F, mean age 37 yr). The difference in [HCO3-] between the two methods was not significant at the 0-, 30-, 45-, or 60-min collections. An excellent correlation in peak [HCO3-] was observed (R2 = 0.84, p < 0.001). Using a peak [HCO3-] cutpoint 80 mEq/L, there was 100% agreement between the methods; using cutpoint 90 mEq/L, there was 83% agreement. CONCLUSIONS: The accuracy of the ePFT is similar to DT: There were minimal differences in [HCO3-] at each of the timed collections and at peak. There is an excellent correlation in peak [HCO3-] and high level of diagnostic agreement between the tests.

Adult↗

Transnasal endoscopy vs. fluoroscopy for the placement of nasoenteric feeding tubes in critically ill patients.

BACKGROUND: Placement of a nasoenteric feeding tube (NET) beyond the pylorus in critically ill patients is desirable. Bedside methods are unreliable, and fluoroscopic methods require transport and/or radiation exposure. Traditional endoscopic methods require sedation and oronasal transfer techniques. Transnasal techniques of NET placement by using recently developed ultrathin endoscopes have been described. The object of this prospective study was to compare the efficacy of NET placement by using ultrathin transnasal endoscopy vs. fluoroscopic placement. METHODS: This is a prospective randomized study of endoscopic vs. fluoroscopic NET placement. The settings of the study were intensive care units at academic medical center. The study included 100 consecutive patients who required NET placement. They received endoscopic NET placement at the bedside with a 5.1-mm, ultrathin endoscope by using a transnasal over-the-wire technique vs. fluoroscopic NET placement by using standard techniques. The procedure success was defined as postpyloric (beyond the duodenal bulb) NET placement, jejunal placement success, and procedure time. RESULTS: Tube placement success was not significantly different between endoscopic and fluoroscopic methods (90% with both methods; p = 1.00). The endoscopic procedure duration (12.8 +/- 6.4 minutes) was significantly shorter than fluoroscopic procedure duration (19.3 +/- 12.0 minutes) (p < 0.001). Procedure duration decreased significantly (from 17.3 +/- 6.2 minutes to 8.0 minutes +/- 4.2 minutes, p = 0.04), and jejunal placement increased significantly (from 60% to 100%, p = 0.04) from the first to the last 10 endoscopic procedures. CONCLUSIONS: NET placement success with an ultrathin transnasal endoscope is equivalent to fluoroscopic placement with faster procedure times. More distal placement and procedure times improve with increasing experience with the endoscopic technique. Endoscopic NET placement can be performed at the bedside without the need for oronasal transfer, additional sedation, or fluoroscopy.

Adolescent↗

Distinct mechanisms for cross-protection of the upper versus lower respiratory tract through intestinal priming.

A main feature of the common mucosal immune system is that lymphocytes primed in one mucosal inductive site may home to distant mucosal effector sites. However, the mechanisms responsible for such cross-protection remain elusive. To address these we have used a model of local mucosal infection of mice with reovirus. In immunocompetent mice local duodenal priming protected against subsequent respiratory challenge. In the upper respiratory tract this protection appeared to be mainly mediated by specific IgA- and IgG2a-producing B cells, whereas ex vivo active effector memory CTL were found in the lower respiratory tract. In accordance with these findings, clearance of reovirus from the lower respiratory tract, but not from the upper respiratory tract, of infected SCID mice upon transfer of gut-primed lymphocytes depended on the presence of T cells. Taken together this study reveals that intestinal priming leads to protection of both the upper and lower respiratory tracts, however through distinct mechanisms. We suggest that cross-protection in the common mucosal immune system is mediated by trafficking of B cells and effector memory CTL.

Administration, Intranasal↗