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Biomedical subjects

N Senninger

Publications and source records attributed to N Senninger.

At least 145 records · Page 8Linked to original sources

Intestinalization of pancreatic fragments in dogs: improvement in survival rate after acute segmental pancreatitis.

Intestinalization, a new method of pancreatic preservation in which vascularized pancreatic fragments are placed inside a jejunal pouch, has been tested for its effectiveness in the prevention of shock and death due to segmental pancreatitis. Intestinalization of the fragment resulted in the survival of eight of nine animals (89 percent) in which recovery was uneventful, whereas animals with pancreatitis in situ or in a mobilized fragment without intestinalization had a mortality rate of 100 percent within 2 days. We conclude that intestinalization ameliorates the outcome of hemorrhagic pancreatitis in the pancreatic fragment by effectively draining toxic products. The procedure may also be useful in pancreatic transplantation since no reintervention is necessary if graft failure or rejection occurs because the pancreas is accessible by endoscopy.

Animals↗

Gastrointestinal motility following small bowel obstruction in the opossum.

The motility of the gastrointestinal tract of six opossums with total and four with partial small bowel obstruction was evaluated. Following the establishment of small bowel obstruction, the migrating myoelectric complex was substituted by a new pattern which was characterized by periods of intense spike activity interspersed with quiescent periods. In the experiments with total intestinal obstruction, the frequency and duration of the periods of intense spike activity were related to the recording site and the time after establishment of intestinal obstruction. The frequency of spike bursts in the ileum proximal and distal to the obstruction was the greatest in the first 2 days after the establishment of the obstruction, while in the antrum and proximal small bowel, the frequency of bursts of spike potentials increased gradually from the first to the fourth postobstruction day (P less than 0.01). However, there was no change in the frequency, duration, and localization of periods of intense spike activity during the 5 days following the establishment of partial intestinal obstruction. We concluded that following intestinal obstruction, the migrating myoelectric complex is substituted by a myoelectric pattern that is characterized by periods of intense spike activity interspersed with quiescent periods. In the animals with total intestinal obstruction, the periods of increased motility are initially more frequent in the bowel proximal and distal to the obstruction and afterwards in the stomach and upper small bowel.

Animals↗

Effect of analgesic drugs on the electromyographic activity of the gastrointestinal tract and sphincter of Oddi and on biliary pressure.

Continuous biliary pressure and electromyographic activity of the sphincter of Oddi and gastrointestinal tract were recorded in conscious opossums following administration of analgesic drugs. Morphine, meperidine, and pentazocin increased significantly the duration of the migrating motor complex (MMC) cycle. Periods of 1-2 minutes of intense burst of spike potentials were seen in the sphincter of Oddi and duodenum following administration of morphine (8 experiments), meperidine (6 experiments), and pentazocin (3 experiments). The biliary pressure in the control studies was similar to that following administration of all analgesics in the animals with gallbladder and following instillation of tramadol, metamizol, and acetylsalicylic acid in animals with no gallbladder. However, the biliary pressure was significantly higher following administration of morphine, meperidine, and pentazocin in the animals with no gallbladder. It is concluded from this study that morphine, meperidine, and pentazocin may cause important disturbances in the motility of the sphincter of Oddi and gastrointestinal tract. These myoelectric disturbances may cause an increase in the biliary pressure in animals that have been subjected to cholecystectomy, but not in animals with intact gallbladder. The gallbladder may accommodate the bile produced by the liver during periods of sphincter of Oddi dysfunction and thus impede an increase in the biliary pressure.

Ampulla of Vater↗

Intestinalization of pancreatic fragments in dogs.

A new operative procedure for the preservation of pancreatic fragments is introduced ("intestinalization") in which vascularized fragments are placed inside a jejunal pouch. This step is done to manage all secretions, lymph and potential debris coming from the pancreas; to maintain the primary portal drainage of insulin; to avoid vascular operations, and to keep the fragment in a denervated state and still preserve its endocrine function to prevent diabetes. The procedure was compared with conventional end to end pancreaticojejunostomy. Sixteen dogs were studied. Group 1 consisted of four dogs that had intestinalization of the pancreatic tail. Group 2 is made up of eight dogs that had complete resection of the remaining duodenal portion of the gland as well as intestinalization of the pancreatic tail. Group 3 consisted of four dogs that had end to end pancreaticojejunostomy to the isolated tail and complete resection of the duodenal portion of the gland as those dogs in group 2. No dog became diabetic during the time of observation (up to one year)--fasting glucose levels and K values in glucose tolerance tests remained normal. Insulin peak values at ten minutes were lower postoperatively. However, return to fasting levels occurred equally fast postoperatively. There was no difference among the groups. The most important morphologic finding in the intestinalized fragments was a firm capsule surrounding the tissue after two weeks. Exocrine atrophy was present in both groups 2 and 3 after one year. No reinnervation of intestinalized pancreas was seen. Intestinalization may offer an alternative to pancreatic resection especially when heterotopic autotransplantation is considered.

Amylases↗

The role of biliary obstruction in the pathogenesis of acute pancreatitis in the opossum.

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.

Acute Disease↗

Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog.

The purpose of our study was to evaluate changes in gallbladder contractility and mucus secretion in vitro during the early stages of gallstone formation in prairie dogs. Thirty-two animals were divided into five groups. Control animals were fed a trace cholesterol diet. Experimental animals were fed a high-cholesterol diet for 3, 6, 8, and 14 days, respectively. Muscle stress was measured in response to cholecystokinin octapeptide in each of the groups. The maximal stresses in the 8-day diet (68 +/- 7 gm/cm2) (mean +/- SEM) and 14-day diet animals (83 +/- 7 gm/cm2) were found to be significantly lower than those of the control animals (137 +/- 12 gm/cm2). The stress in 3-day diet animals was significantly greater (224 +/- 23 gm/cm2). A significant increase in mucus secretion was observed only in 14-day diet animals (11.0 +/- 0.5 X 10(6) dpm/gm dry wt) compared with the control animals (6.4 +/- 1.0 X 10(6) dpm/gm). The decrease in contractility may be the initial event in cholesterol stone formation, and the prolonged exposure of the gallbladder epithelium to crystals may stimulate the release of mucus into the bile.

Animals↗

Effects of gastrointestinal hormones on Oddi's sphincter and duodenal myoelectric activity and pancreatobiliary pressure. Studies in the opossum.

Myoelectric activity of Oddi's sphincter and duodenum was correlated with common duct and pancreatic duct pressures in conscious opossums after infusion of the following substances: cholecystokinin, pentagastrin, glucagon, secretin, and acetylcholine. Cholecystokinin and pentagastrin increased and glucagon and secretin decreased the frequency of spike potentials in Oddi's sphincter and the duodenum. Acetylcholine was associated with the largest increase in spike potentials in both Oddi's sphincter and the duodenum. Although there was variation in the number of pressure elevations related to Oddi's sphincter spike potentials, the baseline pressure remained constant during administration of the hormones. Acetylcholine infusion increased the biliary and pancreatic pressures to 29 and 31 mm Hg, respectively. We conclude that gastrointestinal hormones may have an important role in regulating the excretion of bile and pancreatic juice into the duodenum.

Acetylcholine↗

[Hemorrhagic pancreatitis: effect of dextran 40 and plasma on microcirculation disorders of the pancreas].

A dog model was used to measure the hemodynamic changes occurring during acute pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. Continuous measurements of pancreatic blood flow, cardiac output, mean arterial blood pressure and pancreatic oxygen consumption were made under normal conditions and during acute pancreatitis. All animals received 100 ml of saline/h during the time of observation. Three methods of therapy then were instituted in the dogs starting 30 min after induction of pancreatitis. 10 dogs served as controls (saline 100 ml/h); in 6 dogs additionally 15 ml/kg plasma was infused over 45 min and 6 dogs received 1.5 ml/kg Dextran 40/h continuously. Hemorrhagic pancreatitis was characterized by a fall in cardiac output and mean arterial pressure and the development of severe impairment of the pancreatic microcirculation with early reduction of pancreatic blood flow followed by a fall in pancreatic oxygen consumption. Administration of plasma produced a significant increase in cardiac output; however, blood pressure and pancreatic blood flow remained low. Low-molecular weight Dextran has no influence on cardiac output, but significantly improved the blood pressure and leads to a normalization in pancreatic blood flow and oxygen consumption. These results suggest that low-molecular weight Dextran appears to reverse the impairment of microcirculation and hypoxia of the pancreas and limits the progression from edematous to hemorrhagic pancreatitis and irreversible pancreatic damage.

Animals↗

A new method for correlating pancreatic and biliary duct pressures and sphincter of Oddi electromyography.

Myoelectric activity of the sphincter of Oddi and duodenum was correlated with pancreatic and biliary duct pressures in eight opossums, in both the fasted and fed states. Four bipolar electrode pairs were implanted in the sphincter of Oddi and duodenum. A polyethylene T tube was placed in the pancreatic duct. The common duct was cannulated through a small bile duct. This method allowed pressure recording for several weeks and avoided interference with the flow of bile or pancreatic juice into the duodenum. The frequency of slow waves was the same in the sphincter of Oddi and duodenum (19 per minute). The variation in the frequency of spike potentials in the sphincter of Oddi correlated to that of the migrating myoelectric complex in the duodenum. The average frequency of slow waves that have superimposed spike potentials in the sphincter of Oddi and duodenum was 3.0 and 0 in phase 1, 4.7, and 6.2 in phase II, 6.1 and 15.1 in phase III, and 3.4 and 6.3 in phase IV, respectively. The average duration of a migrating myoelectric complex cycle was 92 minutes. After feeding, the interdigestive phases of the migrating myoelectric complex were abolished and substituted by a feeding activity pattern that was characterized by an average number of sphincter of Oddi and duodenum spikes of 6.6 and 10.7, respectively. The mean fasting pressure in the pancreatic and biliary duct was 15 and 13 mmHg, respectively. Pressure changes were of two types--synchronous with respiratory movements and with each sphincter of Oddi spike potential. There was no variation in the baseline pressure during the migrating myoelectric complex phases and the fed state. It is concluded that the sphincter of Oddi of the fasting opossum exhibits cyclic changes in the number of spike potentials that correlate with the migrating myoelectric complex in the duodenum. However, the number and amplitude of spike potentials are different in the sphincter of Oddi and duodenum. There is no change in the baseline pressure during fasting and feeding states, and a temporary pressure elevation synchronic with each sphincter of Oddi spike potential was observed.

Action Potentials↗

Effect of alcohol upon myoelectric activity of the gastrointestinal tract and pancreatic and biliary duct pressures.

Myoelectric activity of the antrum, duodenum and sphincter of Oddi was recorded from 12 conscious opossums. The common duct and the pancreatic duct were cannulated for pressure measurements. Recordings were made in the fasted state and after gastric or duodenal administration of ethanol. Alcohol was instilled during phase I (55 experiments) or phase II (ten experiments) of the migrating myoelectric complex. Administration of alcohol caused the appearance of phase III-like activity in five to ten minutes in 91 per cent of the experiments. Pancreatic duct and common duct pressure oscillations occurred synchronously with respiratory movements and with sphincter of Oddi spike potentials. There was an increase in the number of pressure elevations related to the increase in sphincter of Oddi spike potentials after alcohol administration; however, base line pressures remained constant. It is concluded that the administration of alcohol into the stomach or duodenum causes the appearance of phase III-like activity and that there is no change in the base line pressure after the instillation of alcohol.

Animals↗

[Peripheral venous tolerance of a hyperosmolar basic solution].

A controlled open clinical trial was carried out to compare the peripheral venous tolerance of patients receiving a hyperosmolar basic nutrition solution (3% amino acids, carbohydrates and electrolytes, 806 mosm/l) with that of patients receiving an isoosmolar electrolyte solution (299 mosm/l). 13 patients received the basic solution, 11 the electrolyte solution. The study was terminated after 4 days. For comparison the infusion time and local venous irritation of each patient were recorded. In both the infusion time and local irritation a slight trend in favour of the electrolyte solution was found, which, however, did not reach statistical significance. We conclude, that under normal clinical circumstances a hyperosmolar basic nutrition solution does not cause a higher rate of peripheral venous irritations compared with an isoosmolar electrolyte solution and should be administered to patients with an expected infusion time of not longer than 4 days.

Amino Acids↗

Gallbladder bile tumor marker quantification for detection of pancreato-biliary malignancies.

BACKGROUND: The pre-operative differentiation of tumors of the pancreas, Papilla of Vater and the biliary tract is still unsatisfactory. Tumor marker analysis of the pancreatic juice did not improve the pre-operative diagnosis by a great deal. METHODS: Bile from resected gallbladders of patients suffering from carcinomas of the pancreato-biliary system was analysed for CA 19-9, CEA, CA 72-4, CA 125 and AFP concentrations. The results were compared to patients suffering from acute cholecystitis, cholecystolithiasis as well as those suffering from benign tumors of the pancreato-biliary region. RESULTS: Extreme high CA 19-9 concentrations were found in bile. Evaluations of the tumor-antigens CA 19-9, CA 72-4 and CEA in gallbladder bile were superior to any serum and pancreatic juice examination with respect to sensitivity and specificity. Observed sensitivities amounted to 100% for patients suffering from bile duct carcinoma (CA 19-9) and papillary carcinoma (CEA) at a specificity of 100%. CA 19-9 showed a sensitivity of 76.5% for pancreatic carcinomas at a specificity of 96.4%. CA 19-9 showed significant differences for the local tumor burden and for the degree of lymph node metastasis. Examination of tumor antigens in the gallbladder results in a high degree of discrimination for malignant and benign lesions of the subhepatic pancreato-biliary system. CONCLUSIONS: CA 19-9 must follow a entero-hepatic circulation, since it showed raised bile concentrations (factor: 10(4)) compared to serum analysis. Analysis of CA 19-9, CEA and CA 72-4 gives an opportunity for improvement in the detection of cancers of the pancreato-biliary system. Since the clinical important differentiation of tumors of the head of the pancreas (carcinoma vs. pancreatitis) remains unclear, an improvement by bile analyses must be assumed.

Antigens, Tumor-Associated, Carbohydrate↗

Analysis of serum CYFRA 21-1 concentrations in patients with esophageal cancer.

BACKGROUND: This study was conducted to determine the use of CYFRA 21-1 for patients suffering from esophageal carcinoma. MATERIALS AND METHODS: 50 patients with malignant, 50 patients with benign esophageal lesions, 50 healthy persons and 50 patients with benign lung disease were tested for CYFRA 21-1, CEA, CA 72-4 and SCC-antigen serum concentrations. The patients with esophageal carcinoma underwent follow-up analysis for one year. RESULTS: CYFRA 21-1 (cut-off: 1.40 ng/ml) showed a sensitivity for esophageal carcinoma of 46% at a specificity of 89.3%. There was a tendency for higher serum CYFRA 21-1 concentrations in advanced T-stages. Correlations of CYFRA 21-1 with N or M stages could not be observed. The postoperative course, in terms of survival and tumor free survival showed significant correlation to pre-operative CYFRA 21-1 concentrations. Adjuvant therapy could be monitored by CYFRA 21-1 as well. Clinical tumor recurrence was preceded by CYFRA 21-1 elevation by 3.4 months. CONCLUSIONS: We recommend the use of CYFRA 21-1 in cases of esophageal carcinoma, especially in cases of squamous cell carcinoma.

Antigens, Neoplasm↗

Expression of MAGE-A cancer/testis antigens in esophageal squamous cell carcinomas.

BACKGROUND: Although the diagnosis and therapy of esophageal cancer have improved over the past decade, the prognosis remains dismal. Since MAGE-A cancer/testis antigens (CTA) are potential targets for immunotherapy, this study was aimed at evaluating their expression in these patients and its prognostic value. MATERIALS AND METHODS: Using 57B monoclonal antibody, MAGE-A CTA expression was analyzed in paraffin-embedded tumor specimens of 98 patients with esophageal squamous cell carcinoma or adenocarcinomas who had undergone surgical resection. For all patients, a postoperative follow-up of at least 4 years was available. The expression was quantified using a scoring system considering intensity and homogeneity of the immunostaining. The prognostic relevance of MAGE-A expression was analyzed in univariate analyses as well as Cox proportional hazard regression analysis. RESULTS: 57B positivity could be detected in 38 tumors (38.8%). Positive staining was observed in five out of 32 adenocarcinomas (15.2%) and in 33 out of 66 (50%) squamous cell carcinomas. MAGE-A expression did not correlate with the TNM classification, grading or age of the patients. Both univariate (p=0.88) and multivariate analyses (p = 0.82) revealed that MAGE-A expression lacked prognostic significance in esophageal carcinomas. CONCLUSION: MAGE-A was expressed in half of the squamous cell carcinomas of the esophagus, but rarely in adenocarcinomas. Although its immunodetection was insufficient for prognostic evaluation, the high expression rate suggests MAGE-A as a potential target for immunotherapy in the first group with the ability for pretherapeutic testing.

Adult↗