Heinz-Juergen Krammer

Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation.

PURPOSE: Several alterations of the enteric nervous system have been described as an underlying neuropathologic correlate in patients with idiopathic slow-transit constipation. To obtain comprehensive data on the structural components of the intramural nerve plexus, the colonic enteric nervous system was investigated in patients with slow-transit constipation and compared with controls by means of a quantitative morphometric analysis. METHODS: Resected specimens were obtained from ten patients with slow-transit constipation and ten controls (nonobstructive neoplasias) and processed for immunohistochemistry with the neuronal marker Protein Gene Product 9.5. The morphometric analysis was performed separately for the myenteric plexus and submucous plexus compartments and included the quantification of ganglia, neurons, glial cells, and nerve fibers. RESULTS: In patients with slow-transit constipation, the total ganglionic area and neuronal number per intestinal length as well as the mean neuron count per ganglion were significantly decreased within the myenteric plexus and external submucous plexus. The ratio of glial cells to neurons was significantly increased in myenteric ganglia but not in submucous ganglia. On statistical analysis, the histopathologic criteria (submucous giant ganglia and hypertrophic nerve fibers) of intestinal neuronal dysplasia previously described in patients with slow-transit constipation were not completely fulfilled. CONCLUSION: The colonic motor dysfunction in slow-transit constipation is associated with quantitative alterations of the enteric nervous system. The underlying defect is characterized morphologically by oligoneuronal hypoganglionosis. Because the neuropathologic alterations primarily affect the myenteric plexus and external submucous plexus, superficial submucous biopsies are not suitable to detect these innervational disorders.

Duodenal infusion of different nutrients and the site of gaseous stimulation influence intestinal gas dynamics

Objective. Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. Material and methods. We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. Results. In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733±26 ml and 541±108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271±78 ml and 96±51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0±0.3 score and 2.3±0.6 score; p<0.05 versus control). Conclusion. Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.

Effect of High- and Low-Caloric Mixed Liquid Meals on Intestinal Gas Dynamics

High-caloric meals can evoke postprandial abdominal complaints involving disturbances in intestinal gas balance. We aimed to determine the influence of the caloric content of meals on intestinal gas dynamics. Eight healthy subjects (five women, three men; age range, 25–43 years) underwent paired studies with low (1 kcal/min)- and high (3 kcal/min)-caloric meal infusion 35% fat, (45% carbohydrate, 20% protein) into the duodenum in random order and proximal jejunal gas infusion. Gas evacuation, perception, and abdominal girth were assessed. The low-caloric meal caused neither gas retention (–7 ± 58 ml) nor girth changes (0 ± 0 mm). In contrast, the high-caloric meal led to significant gas retention (705 ± 56 ml) and increased abdominal perimeter (7 ± 1 mm; P < 0.001 vs. the low-caloric meal for both). Thus, a high caloric load of nutrients arriving at the duodenum modulates both intestinal gas transit and abdominal perimeter.

Effect of Acute Hyperglycemia on Intestinal Gas Transit and Tolerance in Nondiabetic Humans

Background: Acute hyperglycemia usually inhibits gastrointestinal motility and hyperinsulinemia may contribute to specific inhibitory effects. However, the influences on postprandial intestinal gas dynamics have not been investigated. Aims: To compare effects of euglycemic hyperinsulinemia and acute fasting hyperglycemia on intestinal gas dynamics in nondiabetics. Methods: On 3 separate days, 10 healthy volunteers were evaluated in randomized order with duodenal glucose, intravenous glucose or saline infusion. Rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. After 60 min equilibration, proximal jejunal gas infusion (12 ml/min) was started for 150 min. Results: Acute hyperglycemia failed to cause significant intestinal gas retention (72 ± 64 ml and 53 ± 29 ml final gas retention vs. saline); in contrast, gas clearance was expedited, with a maximal effect between 30 and 105 min (p < 0.001 vs. control). Euglycemic hyperinsulinemia did not significantly influence intestinal gas clearance and no relevant changes of abdominal girth or abdominal and rectal perception were seen, as compared to control (p > 0.05 for all parameters). Conclusion: Accelerated intestinal gas clearance under hyperglycemia is one physiologic factor to avoid postprandial intestinal gas accumulation. Specific underlying mechanisms, which need further investigation, may be disturbed in symptomatic patients.

Role of the jejunum versus ileum on intestinal gas dynamics during a balanced meal in healthy subjects.

Under physiological conditions, the human gut adapts intestinal gas propulsion and evacuation to prevent intestinal gaseous complaints In this study we aimed to determine influences of the jejunum versus ileum on intestinal gas dynamics during a balanced meal. Paired studies were randomly performed with seven women and three men, ages 28–42. A mixed liquid meal was infused (1 kcal/min) into the duodenum. After 30 min, gas was infused (12 ml/min) into the jejunum or ileum for 150 min. Gas expulsion was measured, and perception and girth changes were assessed. Postprandial intestinal gas propulsion was uneventful and recovery complete, with −7± 58 and −92± 44 ml final intestinal gas retention for jejunal and ileal gas infusion, respectively. Neither significant differences in abdominal perception nor changes in abdominal girth were seen. During a balanced meal, intestinal gas is effectively propulsed aborally, and this does not depend on the site of the small intestinal stimulation.

Impaired intestinal gas clearance during marked hyperglycemia in patients with functional abdominal bloating.

Background: Especially in patients with functional intestinal disorders, impaired intestinal gas transit can be involved in abdominal symptom generation. We have previously demonstrated an acceleration of intestinal gas clearance in health during acute fasting hyperglycemia and hypothesize that in patients with functional abdominal bloating this mechanism may fail. Methods: In 14 healthy subjects and 14 patients with functional abdominal bloating we compared effects of acute fasting hyperglycemia (∼12 mmol/l) and during euglycemia (control studies) on intestinal gas dynamics. Gas was infused into the jejunum (12 ml/min) for 120 min while rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. Results: Marked hyperglycemia accelerated gas evacuation (–98 (53) ml 1 h intestinal gas retention) in health. In patients with functional abdominal bloating, marked hyperglycemia failed to accelerate gas transit and intestinal gas retention developed (421 (116) ml 1 h intestinal gas retention, p < 0.05 vs. health) which results in increased abdominal symptoms (perception score >3) and abdominal distension (>3 mm girth increment) as compared with control subjects (p < 0.05 for both). Conclusion: Intestinal gas clearance is delayed in patients with functional abdominal bloating and the increase in gas clearance during acute hyperglycemia in healthy volunteers does not occur in these patients.