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Virtual fixtures are virtual constraints that enhance human performance in motion tasks. They can either confine and/or guide a user's motion. In this paper, we use a commercially available motion platform to explore the portability and applicability of virtual fixtures and document how people interact with them. Two micromanipulation tasks are analyzed and the effects of similarly designed virtual fixtures are discussed. One task simulates a medical task, retinal vein cannulation, and the other simulates a manufacturing task, fine leads soldering. Preliminary experimental results show that the virtual fixtures increase the accuracy of both medical and manufacturing tasks, lending support to its portability and applicability across unrelated tasks

Robotic surgical systems such as Intuitive Surgical's da Vinci system provide a rich source of motion and video data from surgical procedures. In principle, this data can be used to evaluate surgical skill, provide surgical training feedback, or document essential aspects of a procedure. If processed online, the data can be used to provide context-specific information or motion enhancements to the surgeon. However, in every case, the key step is to relate recorded motion data to a model of the procedure being performed. This paper examines our progress at developing techniques for "parsing" raw motion data from a surgical task into a labelled sequence of surgical gestures. Our current techniques have achieved90% fully automated recognition rates on 15 datasets.

Anthrax toxin is made up of three proteins: the edema factor (EF), lethal factor (LF) enzymes, and the multifunctional protective antigen (PA). Proteolytically activated PA heptamerizes, binds the EF/LF enzymes, and forms a pore that allows for EF/LF passage into host cells. Using directed mutagenesis, we identified three LF-PA contact points defined by a specific disulfide crosslink and two pairs of complementary charge-reversal mutations. These contact points were consistent with the lowest energy LF-PA complex found by using Rosetta protein-protein docking. These results illustrate how biochemical and computational methods can be combined to produce reliable models of large complexes. The model shows that EF and LF bind through a highly electrostatic interface, with their flexible N-terminal region positioned at the entrance of the heptameric PA pore and thus poised to initiate translocation in an N- to C-terminal direction.

Similar to that of all mammals, the human gastrointestinal tract is colonized by 100 trillion bacteria shortly after birth. Remarkably, in the open-tube arrangement of the intestine, this bacterial population is tightly compartmentalized to the distal gut. Contamination of the small intestine with colonic bacterial flora or small intestinal bacterial overgrowth (SIBO) has been understood previously as a complication of uncommon conditions associated with obvious intestinal stasis. However, SIBO has also been found in 78% to 84% of patients with the common condition of irritable bowel syndrome (IBS). In this paper, the diagnostic and treatment approaches to SIBO are reconsidered within the larger framework of the patient with IBS.

Robotic surgical systems such as Intuitive Surgical’s da Vinci system provide a rich source of motion and video data from surgical procedures. In principle, this data can be used to evaluate surgical skill, provide surgical training feedback, or document essential aspects of a procedure. If processed online, the data can be used to provide context-specific information or motion enhancements to the surgeon. However, in every case, the key step is to relate recorded motion data to a model of the procedure being performed. This paper examines our progress at developing techniques for “parsing” raw motion data from a surgical task into a labelled sequence of surgical gestures. Our current techniques have achieved > 90% fully automated recognition rates on 15 datasets.

Occlusion of feeding tubes is a common and costly complication of enteral feeding. Although the composition of feeding formulas, the size, design, and material of the feeding tube, and the rate of delivery have been considered as factors that determine the rate of tube occlusion, little information is available on the effect of the luminal content of the gut on tube occlusion. Enteral feeding tubes are placed either in the stomach or postpylorically, in the small intestine. The chemical composition of these regions including acidity and bile salt concentration may vary. Since acidity has been shown to promote tube occlusion and bile salts have detergent-like properties, these chemical differences in the luminal environment may be important to tube occlusion. To test the idea that bile salt inhibits acid-promoted occlusion of feeding tubes, in an in vitro study, we compared the time-to-complete occlusion of four groups of formula-filled feeding tubes (six tubes in each group) immersed in an acidic solution (pH 3.0) containing 0 (control), 10, 20, or 40 mM of taurocholate. We found that although 33% of the feeding tubes were occluded within 12 hours in the absence of exposure to bile salt, none were occluded when 20 or 40 mM of taurocholate was added to the acidic solution. After 24 hours, 40 mM of taurocholate inhibited acid-promoted occlusion of 67% of the feeding tubes. Thus 0 to 40 mM of taurocholate still inhibited acid-promoted tube occlusion in a dose-dependent fashion (p < .05). Acidity and the concentration of bile salt may work together, but in opposite directions, as luminal factors that determine the rate of occlusion of feeding tubes.

ContextIrritable bowel syndrome (IBS), which affects 11% to 14% of the population, is a puzzling condition with multiple models of pathophysiology including altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation. Although no conceptual framework accounts for all the symptoms and observations in IBS, a unifying explanation may exist since 92% of these patients share the symptom of bloating regardless of their predominant complaint.Evidence AcquisitionOvid MEDLINE was searched through May 2004 for relevant English-language articles beginning with those related to bloating, gas, and IBS. Bibliographies of pertinent articles and books were also scanned for additional suitable citations.Evidence SynthesisThe possibility that small intestinal bacterial overgrowth (SIBO) may explain bloating in IBS is supported by greater total hydrogen excretion after lactulose ingestion, a correlation between the pattern of bowel movement and the type of excreted gas, a prevalence of abnormal lactulose breath test in 84% of IBS patients, and a 75% improvement of IBS symptoms after eradication of SIBO. Altered gastrointestinal motility and sensation, changed activity of the central nervous system, and increased sympathetic drive and immune activation may be understood as consequences of the host response to SIBO.ConclusionsThe gastrointestinal and immune effects of SIBO provide a possible unifying framework for understanding frequent observations in IBS, including postprandial bloating and distension, altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation.

Slowing of intestinal transit by fat is abolished by immunoneutralization of peptide YY (PYY), demonstrating a key role for this gut peptide. How PYY slows intestinal transit is not known. We tested the hypothesis that the slowing of intestinal transit by PYY may depend on an ondansetron-sensitive serotonergic pathway and a naloxone-sensitive opioid pathway. In a fistulated dog model, occluding Foley catheters were used to compartmentalize the small intestine into proximal (between fistulas) and distal (beyond midgut fistula) half of gut. Buffer (pH 7.0) was perfused into both proximal and distal gut, and PYY was delivered intravenously. Ondansetron or naloxone was mixed with buffer and delivered into either the proximal or distal half of gut. Intestinal transit was measured across the proximal half of the gut. The slowing of intestinal transit by PYY was abolished when either ondansetron or naloxone was delivered into the proximal, but not the distal gut, to localize the two pathways to the efferent limb of the slowing response. In addition, 5-HT slows intestinal transit with marker recovery decreased from 76.2 ± 3.6% (control) to 33.5 ± 2.4% (5-HT) ( P < 0.0001) but was reversed by naloxone delivered into the proximal gut with marker recovery increased to 79.9 ± 7.2% ( P < 0.0005). We conclude that the slowing of intestinal transit by PYY depends on serotonergic neurotransmission via an opioid pathway.

Peptide YY (PYY) is released when PYY cells in short term culture are exposed to fat suggesting that this peptide may be released by fat in the distal gut without neural stimulation. PYY is also released by fat in the proximal 1/2 of small intestine. To test the hypothesis that the release of PYY by fat in the proximal but not distal intestine may depend on an atropine-sensitive, cholinergic pathway, PYY levels were compared in four dogs equipped with duodenal and mid-intestinal fistulas when 60 mM oleate was perfused into either the proximal (between fistulas) or distal (beyond mid-intestinal fistula) 1/2 of gut at 2 ml/min for 120 min with intravenous administration of saline or atropine. We found that, when fat was confined to the proximal 1/2 of the intestine, PYY release was reduced following intravenous atropine when compared with saline (p

We tested the hypothesis that the release of cholecystokinin (CCK) and peptide YY (PYY) may be independent of the region of the small intestine exposed to fat. In five dogs equipped with duodenal and midgut fistulas, the small intestine was compartmentalized so that fat was confined to either the proximal or distal one-half of the gut. Plasma CCK and PYY levels were measured by radioimmunoassay and compared by the square root of the area under the curve (sqrt AUC), representing the plasma peptide concentration over time. CCK was released similarly whether fat was delivered into the proximal (69.9+/-4.7 pM) or distal (71.0+/-5.5 pM) gut, but significantly more CCK (88.9+/-5.6 pM; p0.05) was released when both the proximal and distal gut were perfused simultaneously with fat. PYY was released similarly whether fat was delivered into the proximal (34.9+/-2.6 pM) or distal (40.0+/-1.2 pM) gut or both (38.6+/-2.2 pM). We conclude that CCK and PYY are released by fat in either the proximal or distal one-half of the small intestine.

Previous studies on intestinal electrical stimulation were aimed at achieving a delay in intestinal transit. The aim of this study was to test the hypothesis that the physiological slowing of intestinal transit by the fat-induced ileal brake might be accelerated with intestinal electrical stimulation. This study was performed in five dogs prepared with eight serosal electrodes in the jejunum and two chronic intestinal fistulas located in the duodenum and at the midpoint of the small intestine. To slow transit by triggering the ileal brake, oleate was delivered into the distal half of the gut while buffer was perfused into the proximal half of the gut. Intestinal transit between the fistulas was measured by the recovery of [99mTc]DTPA. To test for the effect of pacing, transit was compared with vs. without continuous forward electrical stimulation (frequency: 24 cycles/min; pulse duration: 50 msec, pulse amplitude 1-3 mA). Electrical stimulation completely entrained intestinal pacesetter potentials as measured fromthe seven recording electrodes distal to the pacing electrode. A substantial and significant increase in intestinal transit was observed with intestinal electrical stimulation with the percentage of marker recovery increasing from 19.2 +/- 9.3% to 84.6 +/- 11.3% (P0.01). In conclusion, intestinal electrical stimulation accelerates intestinal transit slowed by ileal brake.

We have recently found an association between abnormal lactulose breath test (LBT) findings and irritable bowel syndrome (IBS). The current study was designed to test the effect of antibiotic treatment for IBS in a double-blind fashion.Consecutive IBS subjects underwent an LBT with the results blinded. All subjects were subsequently randomized into two treatment groups (neomycin or placebo). The prevalence of abnormal LBT was compared with a gender-matched control group. Seven days after completion of treatment, subjects returned for repeat LBT. A symptom questionnaire was administered on both days.After exclusion criteria were met, 111 IBS subjects (55 neomycin, 56 placebo) entered the study, with 84% having an abnormal LBT, compared with 20% in healthy controls (p0.01). In an intention-to-treat analysis of all 111 subjects, neomycin resulted in a 35.0% improvement in a composite score, compared with 11.4% for placebo (p0.05). Additionally, patients reported a percent bowel normalization of 35.3% after neomycin, compared with 13.9% for placebo (p0.001). There was a graded response to treatment, such that the best outcome was observed if neomycin was successful in normalizing the LBT (75% improvement) (one-way ANOVA, p0.0001). LBT gas production was associated with IBS subgroup, such that methane excretion was 100% associated with constipation-predominant IBS. Methane excretors had a mean constipation severity of 4.1, compared with 2.3 in all other subjects (p0.001).An abnormal LBT is common in subjects with IBS. Normalization of LBT with neomycin leads to a significant reduction in IBS symptoms. The type of gas seen on LBT is also associated with IBS subgroup.

Electrophilic nitration of toluene and benzene was studied under various conditions with several nitrating systems. It was found that high orthopara regioselectivity is prevalent in all reactions and is independent of the reactivity of the nitrating agent. The methyl group of toluene is predominantly ortho-para directing under all reaction conditions. Steric factors are considered to be important but not the sole reason for the variation in the ortho/para ratio. The results reinforce our earlier views that, in electrophilic aromatic nitrations with reactive nitrating agents, substrate and positional selectivities are determined in two separate steps. The first step involves a π-aromatic-NO 2 + ion complex or encounter pair, whereas the subsequent step is of arenium ion nature (separate for the ortho, meta , and para positions). The former determines substrate selectivity, whereas the latter determines regioselectivity. Thermal free radical nitration of benzene and toluene with tetranitromethane in sharp contrast gave nearly statistical product distributions.

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case-control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 +/- 0.8 in IBS subjects and 2.2 +/- 1.0 in controls (P0.000001). The duration of phase III was 305 +/- 123 sec in IBS subjects and 428 +/- 173 in controls (P0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.

Fat has been described to both accelerate and slow intestinal transit. We hypothesized that the fat-induced jejunal brake depends on the combined accelerating effect of CCK and the slowing effect of an opioid pathway. Using a multifistulated model, intestinal transit was measured in four dogs, while 60 mM oleate was delivered into the proximal gut with either 0 or 6 mg naloxone, and 0.1 mg/kg devazepide (a peripheral CCK-A-receptor antagonist) administered intraluminally and intravenously, respectively. In a second study, intestinal transit was measured in seven dogs, while naloxone was delivered intraluminally at 0-, 3-, 6-, or 12-mg doses. Compared to the jejunal brake (marker recovery of 50.1 +/- 2.6%), intestinal transit was slowed by the CCK-A antagonist (36.4 +/- 8.3%; P0.05) and accelerated by naloxone (82.0 +/- 6.8%; P0.05). The accelerating effect of CCK occurred early in the transit response, while the dose-dependent effect (P0.05) of naloxone occurred later. We conclude that fat-induced jejunal brake depends on the early accelerating effect of CCK and the later slowing effect of a naloxone-sensitive opioid pathway.

Posttranslational modification by tyrosine sulfation regulates many important protein-protein interactions and modulates the binding affinity and specificity of seven-transmembrane peptide receptors. We developed a log-odds position-specific-scoring-matrix (PSSM) to accurately predict tyrosine sulfation using 62 tyrosine sites known to be sulfated and 421 tyrosine sites known not to be sulfated. We predict that 49 tyrosines of 32 seven-transmembrane peptide receptors are sulfated. Although we did not incorporate characteristics of confirmed sulfation sites such as clustering and conservation across species into our PSSM, our predicted sites nevertheless exhibited these characteristics. The observed conservation suggests that there are strong evolutionary pressures to preserve selected biological activity of seven-transmembrane receptors. The predicted tyrosine sulfation sites predominantly occur in the extracellular tail and extracellular loop 2, regions consistent with their association with binding pockets of the receptor.

Diffuse esophageal spasm (DES) is an uncommon condition that results in simultaneous esophageal contractions. Current medical treatment of DES is frequently unsatisfactory. We hypothesized that, as a smooth muscle relaxant, peppermint oil may improve the manometric findings in DES.Eight consecutive patients with chest pain or dysphagia and who were found to have DES were enrolled during their diagnostic esophageal manometry. An eight-channel perfusion manometry system was used. Lower esophageal sphincter pressure and contractions of the esophageal body after 10 wet swallows were assessed before and 10 minutes after the ingestion of a solution containing five drops of peppermint oil in 10 mL of water. Each swallow was assessed for duration (seconds), amplitude (mm Hg), and proportion of simultaneous and multiphasic esophageal contractions.Lower esophageal sphincter pressures and contractile pressures and durations in both the upper and lower esophagus were no different before and after the peppermint oil. Peppermint oil completely eliminated simultaneous esophageal contractions in all patients (p0.01). The number of multiphasic, spontaneous, and missed contractions also improved. Because normal esophageal contractions are characteristically uniform in appearance, variability of esophageal contractions was compared before and after treatment. The variability of amplitude improved from 33.4 +/- 36.7 to 24.9 +/- 11.0 mm Hg (p0.05) after the peppermint oil. The variability for duration improved from 2.02 +/- 1.80 to 1.36 +/- 0.72 seconds (p0.01). Two of the eight patients had chest pain that resolved after the peppermint oil.This data demonstrates that peppermint oil improves the manometric features of DES.

Irritable bowel syndrome is the most common gastrointestinal diagnosis. The symptoms of irritable bowel syndrome are similar to those of small intestinal bacterial overgrowth. The purpose of this study was to test whether overgrowth is associated with irritable bowel syndrome and whether treatment of overgrowth reduces their intestinal complaints.Two hundred two subjects in a prospective database of subjects referred from the community undergoing a lactulose hydrogen breath test for assessment of overgrowth were Rome I criteria positive for irritable bowel syndrome. They were treated with open label antibiotics after positive breath test. Subjects returning for follow-up breath test to confirm eradication of overgrowth were also assessed. Subjects with inflammatory bowel disease, abdominal surgery, or subjects demonstrating rapid transit were excluded. Baseline and after treatment symptoms were rated on visual analog scales for bloating, diarrhea, abdominal pain, defecation relief, mucous, sensation of incomplete evacuation, straining, and urgency. Subjects were blinded to their breath test results until completion of the questionnaire.Of 202 irritable bowel syndrome patients, 157 (78%) had overgrowth. Of these, 47 had follow-up testing. Twenty-five of 47 follow-up subjects had eradication of small intestinal bacterial overgrowth. Comparison of those that eradicated to those that failed to eradicate revealed an improvement in irritable bowel syndrome symptoms with diarrhea and abdominal pain being statistically significant after Bonferroni correction (p0.05). Furthermore, 48% of eradicated subjects no longer met Rome criteria (chi2 = 12.0, p0.001). No difference was seen if eradication was not successful.Small intestinal bacterial overgrowth is associated with irritable bowel syndrome. Eradication of the overgrowth eliminates irritable bowel syndrome by study criteria in 48% of subjects.

When toluene reacts with chlorine under experimental conditions that promote free-radical chlorination, a mixture of benzyl chloride, benzal chloride, and benzotrichloride is obtained. The product distribution is determined in large part by the chlorine:toluene ratio. Competing reactions result in chlorination of the aromatic ring, reducing the yield of side-chain chlorination products. Benzyl chloride undergoes reactions typical of a reactive alkyl halide. Hydrolysis gives benzyl alcohol, reaction with ammonia yields benzylamines, and benzyl esters form by reaction with salts of carboxylic acids. Reaction with other nucleophiles yield substitution products; alkoxides give benzyl ethers and cyanide give phenylacetonitrile. Benzal chloride is hydrolyzed to benzaldehyde and benzotrichloride to benzoic acid. Benzotrifluoride is formed by the reaction of benzotrichloride with anhydrous hydrogen fluoride. Reaction conditions have been determined for aromatic ring chlorination and nitration of benzyl chloride, benzal chloride, and benzotrichloride. More than two-thirds of benzyl chloride produced is used to make the plasticizer benzyl butyl phthalate. Nearly all of the benzal chloride produced is consumed in the manufacture of benzaldehyde. Benzotrichloride is used in the manufacture of benzoyl chloride and in the synthesis of the herbicide intermediate p-chlorobenzotrifluoride.

The preparation, physical and chemical properties, and applications on mono-, di-, tri-, tetra-, and pentachlorotoluenes are reviewed. Reactions of chlorotoluenes are classified into those involving the aromatic ring, the methyl group, and the halogen. The reactions involving the methyl group are widely used to synthesize a variety of functionalized chloroaromatic compounds. Some of the recent applications of these compounds are based on replacement of the halogen by other functional groups catalyzed by transition-metal compounds. Monochlorotoluenes are obtained generally by reaction of toluene with chlorine under a variety of homogeneous and heterogeneous conditions. The higher chlorotoluenes are obtained usually by chlorination of the lower chlorinated analogues. Many detailed studies have been conducted to evaluate the toxicological properties of chlorotoluenes. Ring-chlorinated toluenes find principal applications in the pesticide, pharmaceutical, peroxide, dye, and other industries. p-Chlorotoluene is an especially valuable starting material to prepare numerous, industrially useful intermediates.

We tested the hypothesis that the release of PYY by fat confined to the proximal small intestine is dependent on CCK. Using a multi-fistulated model, plasma PYY levels were compared in 6 dogs after 60 mM oleate was perfused into the proximal one-half of the small intestine following i.v. administration of saline or devazepide, a CCK-A antagonist. Plasma PYY increased with fat (P < 0. 05), but plasma PYY level was lower following devazepide at 60 min and 90 min (P < 0.05). We conclude that CCK serves as a foregut signal linking fat in the proximal gut with the release of distal gut PYY.

The "ileal brake" is the primary inhibitory feedback mechanism to control transit of a meal through the gastrointestinal tract in order to optimize nutrient digestion and absorption. Neurohormonal factors mediating this response continue to be identified. Recently, additional brakes that fine-tune transit have been described. When gut traffic control is disrupted, pathologic states characterized by malabsorption and impaired drug bioavailability manifest as diarrhea and malnutrition. An understanding of the importance of these nutrient-triggered brakes provides essential clues to future treatments of chronic diarrhea, malnutrition, and drug malabsorption.

The first modern description of dyspepsia (1), described it as an “episodic or persistent” abdominal pain in the absence of bleeding or jaundice. Since then, various descriptions have been used (2, 3). These definitions include symptoms of peptic ulcer disease in a subject without an ulcer (2) and upper abdominal pain with a lack of identifiable cause (3). In 1989, Barbara, et al. once again tried to define NUD (dyspepsia) as episodic or persistent abdominal symptoms often related to feeding, which patients or physicians believe to be due to disorders of the proximal portion of the digestive tract (4). More recently, groups have tried to sub-categorize NUD into categories such as reflux-like, dysmotilitylike, ulcer-like (5,6) and even irritable bowel-like (7).

Soy protein, in both intact and hydrolyzed forms, is widely used as the nitrogen source in infant and adult formulas. This protein is also consumed in vast quantities worldwide as soybean-based food products. Digestion is the rate-limiting step in the assimilation of proteins from the gut. As a result, intestinal transit must be slowed when a higher load of protein is available or when this nutrient is delivered in the intact rather than hydrolyzed form. However, little information is available on the effect of load and degree of hydrolysis of soy protein on intestinal transit and protein absorption. To test the hypothesis that inhibition of intestinal transit and protein absorption depend on the load of soy protein and the state of hydrolysis of this nutrient, we compared intestinal transit and protein absorption in dogs equipped with duodenal and midintestinal fistulas during intestinal perfusion with 0, 50, 100, or 200 g/L solutions of intact soy protein versus 0, 100, 200, 300, or 400 g/L solutions of hydrolyzed soy protein. We found that intestinal transit was slowed in a load-dependent fashion by intact (P < 0.001) and hydrolyzed (P < 0.05) soy protein. Soy protein inhibited intestinal transit more potently in the intact than hydrolyzed form (P < 0.05). A greater amount of protein was absorbed by the proximal half of the small intestine when soy protein was delivered in the hydrolyzed than intact form (P < 0.05), and the efficiency of protein absorption was maintained at a high and nearly constant level of 82.6 to 87.4% for intact soy protein and 89.0 to 92.3% for hydrolyzed soy protein. We conclude that in dogs intestinal transit and absorption of soy protein depend on the load and the degree of protein hydrolysis.

Diabetic gastroparesis with nausea and vomiting that is unresponsive to medical therapy is one of the more challenging complications of diabetes. Repeat visits to the emergency department, numerous hospital admissions, and enteral feeding (1) add to the debility already associated with this condition. Although patients with such severe symptoms are few (2), a poor prognosis is often associated with the diagnosis. Reports of increased mortality among diabetic patients with autonomic neuropathy (3), and the association of diabetic gastroparesis with autonomic neuropathy (4), contribute to this expectation of a poor prognosis for diabetic patients with delayed gastric emptying. Furthermore, the term “gastroparesis” suggests permanent paralysis of the stomach. There are several reasons to reexamine the idea that patients with diabetic gastroparesis have a poor prognosis. First, gastric emptying is impaired by hyperglycemia. The rate of gastric emptying in patients with type 1 diabetes decreases during periods of hyperglycemia (5). The triggering of a gastric electrical rhythm disturbance may be a key mechanism in this hyperglycemia-induced but reversible effect (6). Second, hyperglycemia also leads to reversible impairment in autonomic nerve function. In normal volunteers who underwent glucose clamping to raise their blood glucose levels to the hyperglycemic range, cardiovascular nerve function was impaired (7). Third, normalization of blood glucose levels with pancreas transplantation restores autonomic nerve function in some patients (8,9). Fourth, delayed gastric emptying has not been observed to increase mortality in patients with type 1 or type 2 diabetes (10). When considered together, these reports suggest that patients with diabetic gastroparesis include both those with irreversible and those with reversible (hyperglycemia-induced) impairment of gastric emptying. Jones et al. (11) in this issue of The American Journal of Medicine addresses some of these questions. They studied 20 patients with type 1 or type 2 diabetes, comparing rates of solid and liquid emptying, blood glucose concentration, gastric and esophageal symptoms, and autonomic nerve function at baseline and at follow-up about 12 years later. They found that during this time, there was minimal change in gastric emptying for solids and liquids, glycemic control was mildly improved, there was no change in gastric or esophageal symptoms, and autonomic nerve function worsened. This is an important study from a group that has made notable contributions to our understanding of the effects of diabetes on gastrointestinal motility. Extending their previous work that showed that diabetic gastroparesis was not associated with increased mortality (10), their results further support the promise of a good prognosis for diabetic patients with delayed gastric emptying. Does a good prognosis apply to all diabetic patients with delayed gastric emptying? Likely not. In patients who had undergone pancreas transplantation successfully (9), gastric function, as measured by gastric emptying and electrogastrography, did not improve in about half of patients. However, it is encouraging that even in a group of patients with very severe diabetes and refractory complications, not every patient with delayed gastric emptying had a poor prognosis. An intriguing finding of their study is that autonomic nerve function worsened even as the rate of gastric emptying remained unchanged. This lack of a correlation between the recorded change in autonomic nerve function and the change in gastric emptying raises additional doubts about the suggestion that diabetic gastroparesis, in most patients, is paresis of the stomach due to autonomic neuropathy. Because hyperglycemia may have been responsible for a reversible delay in gastric emptying, future studies in this area should consider adding glucose clamping to their design. With patients maintained at normal blood glucose concentrations, it would be possible to sort patients into either the reversible or irreversible impairment group. Adjusting for the confounding effects of hyperglycemia would allow testing of the hypothesis that a good prognosis may apply to the reversible impairment group but not the irreversible group. As we continue to learn more about this relationship, perhaps the term “diabetic gastroparesis” will eventually be reserved for the rare patient with irreversible paresis of the stomach. Am J Med. 2002;113:525–526. From the GI Motility Program and Section of Nutrition, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, and Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Requests for reprints should be addressed to Henry C. Lin, MD, 8635 W. Third Street #770W, Los Angeles, California 90048, or henry.lin@cshs.org.

The slowing of gastric emptying by hyperosmolar solutions has been postulated to result from the triggering of duodenal osmoreceptor feedback on the stomach. We tested the idea that the inhibition of gastric emptying by a hyperosmolar solution depended on the duodenal resistance and the triggering of nutrient-specific feedback by tracking gastric emptying of 300 and 1,200 mosmol/kgH2O test solutions in 12 dogs in which duodenal resistance was either removed (by temporarily diverting chyme from uncorked duodenal fistula) or preserved (by keeping duodenal fistula corked). Mannitol was used to test osmolality alone, and glucose was used to examine the combined effects of osmolality and nutrient-specific inhibitory feedback. We found that: 1) the slowing effect of hyperosmolality was more marked with the duodenal resistance preserved (P < 0.05; analysis of variance), 2) the slowing effect of glucose was greater than that of mannitol for all conditions (P = 0.01; analysis of variance), and 3) the inhibitory effect of mannitol was localized to the duodenum. We conclude that inhibition of gastric emptying by hyperosmolar mannitol depended primarily on duodenal resistance, while the inhibitory effect of hyperosmolar glucose depended on nutrient-specific feedback on the stomach more than duodenal resistance.

TO THE EDITOR: We thank Dr. Jones and his colleagues for their interest in our article and take this opportunity to address some of their concerns and respond to their comments.