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Biomedical subjects

K H Soergel

Publications and source records attributed to K H Soergel.

At least 19 recordsLinked to original sources

Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

Adult

Colonic fermentation: metabolic and clinical implications.

Colonic SCFA formation from fermentable carbohydrate is important for the maintenance of morphologic and functional integrity of the colonic epithelium. Carbohydrate-induced diarrhea occurs when the amount of carbohydrate entering the colon exceeds its fermentation capacity. Deficient availability or utilization of SCFA, mainly of n-butyrate, is the cause of diversion colitis and may play important roles in colonic carcinogenesis, in starvation and enterotoxigenic diarrhea, and in idiopathic UC.

Acetates

[Diagnostic guidelines in diarrhea].

Acute diarrhea is usually short-lasting; therefore, diagnostic procedures are mainly concerning the degree of dehydration. With longer duration of high fever or bloody diarrhea, microbiologic stool tests are necessary. Proctosigmoidoscopy is indicated in case of dysenteric disease or suspected antibiotic-as-associated pseudomembranous colitis. In chronic diarrhea, the most important diagnostic procedure is a careful history. Side effects of drugs and food-related causes are especially noticeable, as are indices of an organic origin, e.g. unwanted weight loss or blood in the stools. Also, careful history and physical examination are essential for the decision about laboratory tests, tests of gastrointestinal function or endoscopy.

Acute Disease

Lithotripsy versus cholecystectomy for management of gallstones. A decision analysis by Markov process.

Extracorporeal shock-wave lithotripsy is a new treatment method that effectively distintegrates radiolucent gallstones and is associated with a low complication rate. Using the model of a Markov process for decision analysis, survival and costs under four possible strategies to treat gallstones were compared: expectant management with cholecystectomy (EC) or lithotripsy (EL) reserved for symptomatic gallstones; prophylactic cholecystectomy (PC) or lithotripsy (PL) for all gallstones. Life expectancy for the different strategies varies by few days. Only if high annual rates of pain and complication occurred in subjects with silent gallstones would both prophylactic procedures marginally increase life expectancy. Prophylactic cholecystectomy then would be more cost-effective than prophylactic lithotripsy. Expectant strategies remain much cheaper than prophylactic management over a broad range of probability values and procedural costs. Expectant use of lithotripsy costs less than cholecystectomy. A low success rate of lithotripsy would raise the direct costs of lithotripsy above those of cholecystectomy but leave total costs of both strategies in the same order of magnitude. Lithotripsy appears to be a feasible alternative to treat symptomatic but not asymptomatic gallstones.

Adult

Gastrointestinal motor effects of erythromycin in humans.

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Abdominal Pain

Transport of propionate by human ileal brush-border membrane vesicles.

Human ileal brush-border membrane vesicles were employed to study the mechanisms of short-chain fatty acid (propionate) absorption especially to determine the effects of intravesicular HCO3- and the component of nonionic diffusion. Preloading the vesicles with HCO3- resulted in up to 20-fold "overshoots" of transport, and this effect was not seen with other intravesicular anions. This transport process was very fast (peak uptake 6 s) and was not due to intravesicular buffering by HCO3-. Radiolabeled propionate transport demonstrated transstimulation when the vesicles were preloaded with unlabeled propionate. An inward H+ gradient led to stimulation of propionate transport much smaller than in the presence of trans-HCO3-, whereas an inward Na+ gradient had no effect. Propionate transport was attenuated by the anion exchange inhibitors SITS and DIDS. Under HCO3- gradient conditions, propionate transport exhibited saturation kinetics with an apparent Km of 21 +/- 3 mM and a Vmax of 50 +/- 3 nmol.mg protein-1.3 s-1. Propionate transport was inhibited up to 40% by 2-5 carbon short-chain fatty acids (10 mM) but not by other organic anions. Short-chain fatty acid transport in the human ileum is Na+ independent and occurs mostly via a specific anion exchange mechanism with HCO3-. Our results also demonstrate a small component of nonionic diffusion of the protonated fatty acid (or anion exchange for OH-).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Treatment of diversion colitis with short-chain-fatty acid irrigation.

A condition known as diversion colitis frequently develops in segments of the colorectum after surgical diversion of the fecal stream; it persists indefinitely unless the excluded segment is reanastomosed. The disease is characterized by bleeding from inflamed colonic mucosa that mimics the bleeding of idiopathic inflammatory bowel disease, and it may culminate in stricture formation. We hypothesized that this condition is caused by the absence of luminal short-chain fatty acids, the preferred metabolic substrates of colonic epithelium. We studied four patients with diversion colitis, none of whom had evidence of Crohn's, idiopathic ulcerative, or infectious colitis. The excluded segment of the rectosigmoid contained negligible concentrations of short-chain fatty acids. When D-glucose was instilled, it did not undergo appreciable anaerobic fermentation. Instillation of a solution containing short-chain fatty acids twice daily resulted in the disappearance of symptoms and the inflammatory changes observed at endoscopy, over a period of four to six weeks. Remission has been maintained for up to 14 months (in one patient) by instillation daily to twice weekly. Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis. Histologic observation revealed a distinctive type of mucosal inflammation that resolved more slowly and less completely than the gross appearance of the inflamed mucosa. From these preliminary studies we infer that diversion colitis may represent an inflammatory state resulting from a nutritional deficiency in the lumen of the colonic epithelium, which is effectively treated by local application of short-chain fatty acids, the missing nutrients.

Colitis

D-glucose and L-leucine transport by human intestinal brush-border membrane vesicles.

This study utilized intestinal brush-border membrane vesicles obtained from organ donor intestine to characterize the absorption of D-glucose and L-leucine in the human intestine. Both D-glucose and L-leucine were taken up by sodium gradient-dependent active transport along the entire length of the small intestine. The relative magnitude of transport for both substrates under sodium gradient conditions followed the order distal jejunum greater than proximal jejunum greater than distal ileum. The number of carrier systems in these brush-border membrane vesicles was estimated by Eadie-Hofstee plot analysis. This analysis revealed that L-leucine was actively transported via a single high-affinity transport system for the length of the human small intestine. In contrast, the transport of D-glucose occurred via a high-affinity system along the length of the intestine and via a low-affinity, high-flux transport system that was limited to the proximal intestine. Both glucose transport systems were sodium dependent and phlorizin sensitive. The locations and apparent kinetic parameters of these transport systems indicated that these systems function efficiently in vivo as important mechanisms for carbohydrate and protein assimilation in humans. The presence of these active transport systems along the entire small intestine explains the formidable capacity for carbohydrate and protein assimilation in humans.

Biological Transport, Active

Spatial and temporal patterns of human jejunal contractions.

We recorded human jejunal motor activity by a 12-lumen manometric tube with recording sites 2 cm apart. The contractile activity in the fasted and the fed state was analyzed by computer to define the spatial and temporal patterns of contractions. Mean duration and area of single contractions during phase III activity were not different from those during phase II activity. By contrast, the frequency and amplitude of contractions, their propagation distance, and the percentage of contractions that propagated for greater than or equal to 2 cm were significantly greater during phase III than during phase II activity. The mean frequency and percentage of propagated contractions in the fed state were intermediate between those during phase II and phase III activity. Mean propagation distance of postprandial contractions was not different from that of phase II contractions. Most contractions in the fed state were uncoordinated at adjacent recording sites. Occasionally, large-amplitude and long-duration contractions, called individual migrating contractions, propagated over long distances and frequently over the entire 22-cm study segment. We conclude that there are some significant differences between the spatial and temporal patterns of contractions between the fed state and phase II and phase III activity. The largely disorganized phasic contractions in the fed state may cause mostly mixing of the ingested meal and its slow distal propagation, whereas the infrequent individual migrating contractions may rapidly propel intestinal contents over longer distances.

Adult

Brush border membrane vesicles formed from human duodenal biopsies exhibit Na+-dependent concentrative L-leucine and D-glucose uptake.

The human duodenum actively transports L-leucine and D-glucose under Na+ gradient conditions as demonstrated by uptake studies using brush border membrane vesicles from organ donor duodenum. Brush border membrane vesicles formed from peroral duodenal biopsies likewise demonstrate Na+ dependent concentrative uptake of D-glucose and L-leucine. This is the first demonstration of active transport processes in human duodenum. A simple microvesiculation method to form these vesicles is described as well as its potential application to clinical medicine in studying diseases of defective intestinal transport.

Biological Transport

Contraction pattern of opossum gallbladder during fasting and after feeding.

Our major aims in this study were to determine in unanesthetized opossums the gallbladder volume, pressure, and tone during fasting as well as after feeding, model the kinetics of changes in gallbladder volume, and correlate gallbladder contractility with concurrent spike burst activity in the upper gastrointestinal tract and sphincter of Oddi (SO). In 10 animals, we implanted electrodes on the gastric antrum, duodenum, SO, and jejunum. An indwelling catheter monitored gallbladder pressure and volume. In two animals, a force transducer sutured to the gallbladder wall monitored gallbladder tone. In each animal, fasting migrating myoelectric complexes (MMCs) were recorded in the stomach and small bowel. Cyclic changes in SO spike bursts occurred in synchrony with the MMCs. During fasting, gallbladder pressure, tone, and volume showed cyclic variations. During the second half of the duodenal MMC cycle, the gallbladder exhibited phasic as well as tonic contractions associated with net gallbladder emptying, whereas during the first half of the cycle the gallbladder relaxed and refilled. Minimal gallbladder volume during the MMC cycle averaged 4.8 +/- 0.7 (SE) ml compared with a maximal volume of 7.0 +/- 0.9 ml. Decreases in gallbladder volume occurred as an exponential function, whereas increases in gallbladder were linear. After feeding, the gallbladder underwent a sustained tonic contraction, without superimposed phasic contractions. Decreases in gallbladder volume occurred exponentially to a residual volume of 2.0 +/- 0.5 ml. Net postprandial gallbladder emptying was maximal by 40 min; then the volume remained unchanged for 2-3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Multipeaked esophageal peristaltic pressure waves in patients with diabetic neuropathy.

We evaluated esophageal function in 14 consecutive insulin-dependent diabetic patients who had evidence of peripheral and autonomic neuropathy, but no esophageal symptoms. One to three contraction waves immediately followed a primary peristaltic contraction wave. The majority of these multipeaked pressure complexes consisted of two peaks. Multipeaked contractions were observed with all peristaltic waves in 12 of the 14 diabetic patients and with most of the peristaltic complexes in the remaining 2 patients. Multipeaked peristaltic waves were present in 1 of 6 diabetic patients without neuropathy, in 1 of 100 consecutive nondiabetic patients referred for suspected esophageal disease, and in 1 of 10 healthy volunteers. Double-peaked peristaltic pressure complexes in the nondiabetic control subjects differed from those present in the insulin-dependent patients by their low incidence and by a tendency to be limited to the distal esophagus. Pharmacologic responses to edrophonium and atropine suggested a possible increased cholinergic tone as the basis of the multipeaked peristaltic waves in diabetics with autonomic neuropathy.

Adolescent

Role of endoscopic retrograde cholangiopancreatography in the diagnosis and treatment of choledochocele.

Choledochocele is a rare abnormality involving the intramural segment of the common bile duct. It may present clinically as recurrent acute pancreatitis, biliary colic, or cholestatic jaundice. A choledochocele may be easily overlooked by the conventional diagnostic methods, such as upper gastrointestinal series, intravenous cholangiogram, abdominal ultrasound, and computed tomography. Endoscopic retrograde cholangiopancreatography is helpful in demonstrating a choledochocele. Additionally, in selected cases, a choledochocele may be effectively managed by endoscopic sphincterotomy. We present the clinical, endoscopic, and radiographic findings in a series of 8 patients with choledochocele. The radiologic technique most useful in demonstrating a choledochocele at the time of endoscopic retrograde cholangiopancreatography is detailed. The pathogenesis, differential diagnosis, and relevant current literature pertaining to choledochocele are discussed.

Aged