Is superior graft survival of multiorgan donor kidneys due to better preservation or better organ selection?
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Biomedical subjects
Publications and source records attributed to W Niebel.
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The introduction of immunosuppression with cyclosporine A in 1983 compared to conventional immunosuppression has clearly improved early results within the first year post transplant. In contrast, the rate of graft failure per year in the following course has not changed essentially. Still HLA histocompatibility is a predominant prognostic factor which can be influenced by organ sharing. On the other hand, donor factors like sex and age are becoming more important and should be taken into account for organ allocation. This furthermore requires strict attention to future exchange rules within the transplant community.
Little is known about the influence of cutting the extrinsic pancreatic nerves on the morphology and function of the intrapancreatic nerves in dogs. For this reason, intrapancreatic nerves of mongrel dogs were studied, using electron microscopy and immunohistochemistry, after truncal vagotomy, after celiac and superior mesenteric ganglionectomy, and after a combination of both operations, i.e., removing all extrinsic nerves of the pancreas. Dogs with intact extrinsic and intrinsic pancreatic nerves served as controls. Studies were performed 1-2 weeks and up to 5 months after one or both denervation procedures. For immunohistochemical and electron microscopic studies the animals were perfused with glutaraldehyde-formaldehyde-picric acid solution and the tissue was embedded in Epon or paraffin. Both immunohistochemical and electron microscopic studies revealed that signs of degenerating intrapancreatic nerves occurred only in the early phase (up to 30 days) after operation. After 60 days, hypertrophy of pancreatic nerve fibers was observed. The most striking finding was that the integrity of the intrapancreatic ganglia and nerves was almost preserved after complete extrinsic denervation. In controls there was a strong intrapancreatic innervation with vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), substance P (SP), and neuropeptide Y (NPY) nerves. SP and NPY-nerves significantly decreased after the different denervation procedures, but the other peptidergic nerves were not altered by truncal vagotomy, ganglionectomy, or the combination of both procedures. We conclude that the dog pancreas contains extensive intrinsic peptidergic nerves, which, with the exception of SP and NPY-nerves, are greatly independent of the integrity of the extrinsic nerves.
To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HCl (1.5 to 48 mmol h-1) were performed with and without atropine (14 nmol kg-1 h-1 i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h-1 of HCl and was significantly (p less than 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HCl in dogs with a denervated jejunoileum. HCl caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12-48 mmol h-1) of HCl were given. Atropine significantly reduced these responses.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was undertaken to determine the role of cholecystokinin in pancreatic enzyme secretion stimulated by bombesin and a meal by (a) comparing the pancreatic enzyme output during bombesin infusion and after a meal to output during caerulein infusion and (b) comparing the inhibitory effect of the cholecystokinin-receptor antagonist lorglumide (CR-1409) on enzyme output in response to bombesin and food with the response to caerulein. Bombesin (90 pmol/kg per h) and caerulein (30 pmol/kg per h) were infused into seven dogs in doses giving similar plasma cholecystokinin peak increments as a meal (mean (SEM) 6.8 (0.8), 6.3 (1.2), and 5.7 (0.8) pM, respectively), together with either saline or 2 mg/kg per h of lorglumide. A background infusion of synthetic secretin 20.5 pmol/kg per h was given in each experiment. In addition, gastric acid secretion was determined in the experiments with bombesin and caerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h) and food (1430 (220) mg/h) were similar to the responses to caerulein (1249 (201) mg/h). Lorglumide inhibited pancreatic protein output during stimulation with bombesin by 60%, after the meal by 45%, and during caerulein infusion by 68%. Pancreatic bicarbonate output by bombesin, caerulein, and food was inhibited by lorglumide by 28%, 40%, and 38%, respectively. In contrast, lorglumide significantly increased gastric acid secretion from 1.12 to 7.98 mmol/h during bombesin infusion and from 0.52 to 7.62 mmol/h during caerulein infusion. In conclusion, cholecystokinin plays an important part in the stimulation of pancreatic enzyme secretion by bombesin and a meal in conscious dogs and it is involved in the regulation of gastric acid during stimulation by infusions of caerulein and bombesin.
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Veno-venous bypass during orthotopic liver transplantation is commonly performed as a porto-femoro-axillary bypass. Right-angle positioning of one patient's arm and surgical preparation of the femoral and axillary veins are necessary. In 17 patients and 20 consecutive orthotopic liver transplant procedures the common porto-femoro-axillary veno-venous bypass was substituted by porto-femoro-subclavian bypass with a percutaneous 20 F cannulation set (LAUB catheter, Cook). The 20 F catheter was introduced into the left subclavian vein by Seldinger's technique before the operation and was connected intraoperatively to the outflow tube of the biopump. Surgical preparation of the axillary vein was not performed. In 10 patients a Y-connector was used to connect up the Rapid Infusion System in addition. Postoperatively the catheter was left in place for 2-4 days. Introduction and removal of the catheter were uneventful in all cases. High blood flow through the catheter could be maintained by a low driving pressure of the pump (4000 ml/min; 100 mmHg). No intraoperative complications were observed. Shunt flows remained stable throughout the surgical procedure during the anhepatic stage. There was no bleeding from the puncture site, especially after removal of the catheter, though several patients had a poor coagulatory status in the early postoperative period. Two postoperative complications were observed: air embolism due to disconnection and formation of a thrombus at the catheter tip, which it was possible to remove together with the catheter itself. Installation of an irrigation infusion in the postoperative period and well-tightened connections help avoid such complications as thrombus formation, bleeding or air embolism.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was undertaken to delineate the role of cholecystokinin (CCK) in bombesin- and meal-stimulated pancreatic polypeptide (PP) secretion in seven conscious dogs by studying: (1) the stimulatory effect of similar plasma levels of CCK induced by a meal and infusions of bombesin and the synthetic CCK analog cerulein on plasma PP, and (2) the inhibition of PP secretion by the CCK-receptor antagonist CR-1409 during these three stimuli. The stimulation of PP secretion during bombesin (11.0 +/- 1.6 nM/hr) and after the meal (8.9 +/- 2.0 nM/hr) were significantly (P less than 0.05) greater than during infusion of the CCK analog cerulein (2.7 +/- 0.4 nM/hr). CR-1409 significantly inhibited the bombesin- and meal-stimulated PP secretion to 2.0 +/- 0.4 nM/hr (81%; P less than 0.05) and 3.1 +/- 1.2 nM/hr (47%; P less than 0.05), respectively, while the cerulein-stimulated PP release was almost abolished to 0.2 +/- 0.1 nM/hr (93%; P less than 0.05) by the drug. These findings point to an important role for CCK in the regulation of bombesin- and meal-stimulated PP secretion.
Acid extracts of human intestines obtained from surgical samples or from organ donors contain cholecystokinin (CCK) immunoreactivity. From surgical samples, extracted and eluted quickly, greater than 75% of the CCK immunoreactivity eluted in the same region as purified canine CCK-58 during analytical reverse-phase high-pressure liquid chromatography (HPLC). A major portion of the CCK immunoreactivity from donor intestinal extracts also eluted in this region. This immunoreactivity has been purified from human intestinal extracts by a series of several reverse-phase and cation-exchange chromatographies. Amino acid and microsequence analysis showed that this immunoreactivity is human CCK-58. Tryptic digestion of purified human CCK-58 produced another immunoreactive form that eluted in the position of CCK-8 during analytical reverse-phase HPLC. The immunoreactivity of the trypsin-digested material was 2.6-fold higher than that of an identical sample of CCK-58 incubated without trypsin. Thus the carboxyl-terminal antibody used for radioimmunoassay cross-reacts greater than twofold less with human CCK-58. This diminished cross-reactivity would lead to an underestimation of the relative proportions of CCK-58 in tissue and plasma extracts. If CCK-58 is the major circulating form this diminished cross-reactivity would also lead to underestimations of the circulating levels of total CCK. Determination of human CCK-58 structure confirms that one of the major components of human CCK that expresses biological activity is CCK-58.
In six to nine mongrel dogs the effect of graded doses of intravenous neurotensin (188, 375, 750, and 1500 pmol/kg h) on acid secretion basally or stimulated by distention (by isotonic glucose), peptone (0.5, 1, and 4 g%), and pentagastrin was studied. Neurotensin did not affect acid secretion basally, stimulated by distention, or the maximal peptone dose. However, when submaximal doses (0.5 and 1 g%) of peptone were instilled in the stomach, neurotensin stimulated the secretory response to intragastric peptone. This effect was observed in doses of intravenous neurotensin which mimicked circulating neurotensin concentrations after a standard test meal. Thus, neurotensin could be considered a physiologic stimulant of acid secretion when protein is present in the stomach. The mechanism for this action of neurotensin is unknown but could be partly explained by an enhanced release of gastrin. The potentiating effect of neurotensin on peptone-stimulated acid secretion could play a major role in gastric secretory function of the dog.
We report two cases of primary malignant melanoma of the esophagus. Both were female, 83 and 68 years of age. Both had metastatic spread of the disease at the time of first treatment, either in regional lymph nodes or organ involvement. One patient underwent resection of the tumor (partial esophagectomy). The second patient is alive 22 months postoperatively with metastatic tumor (12/1989), the first died one year after diagnosis. Prognosis of primary melanoma of the esophagus is poor. Though, resection of the tumor is the most promising therapy.
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