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Biomedical subjects

H G Gooszen

Publications and source records attributed to H G Gooszen.

At least 145 records · Page 8Linked to original sources

Interference by cyclosporine with the endocrine function of the canine pancreas.

This study addresses itself to the eventual interference of cyclosporine (CsA) with the function of pancreatic beta cells in vivo. We have used dogs that had at least six weeks previously been subjected to segmental pancreatic autotransplantation. This model has been well established to be associated with stable normoglycemia but with incomplete endocrine reserve capacity, which renders it suitable for detecting eventual toxic drug effects. CsA was administered for 6 weeks in an oral dose of either 30 mg/kg/day (first series of 4 dogs) or 40 mg/kg/day (second series of 7 dogs). CsA trough levels in blood were determined at least weekly, and the mean of the levels in each dog ranged from 218 to 1274 ng/ml, with one exception (2191 ng/ml). The endocrine function was tested not only before and after 6 weeks of CsA administration, but also at 4 weeks after cessation of CsA administration. The postprandial insulin output was reversibly reduced in the first series (P less than 0.05) and the i.v. glucose-stimulated insulin output was reversibly reduced in the second series (P less than 0.001). Other parameters, like postprandial peak and mean blood glucose levels and K-values, showed reversible changes that, although not always statistically significant, were compatible with a reversible suppressive effect by CsA in all instances. Finally, we found that the severity of suppression as expressed in individual reduction of i.v. glucose-stimulated insulin output correlated with the individual mean CsA trough level (r = 0.71, P less than 0.015). It is concluded that CsA exerts a detrimental effect on the function of canine beta cells in vivo, which effect is reversible and dependent upon the CsA blood level.

Animals↗

Pancreatic duct obliteration: clinical application, morphological and functional effects.

Pancreatic duct obliteration is a procedure to abolish exocrine secretion in order to prevent complications such as leakage, abscess and fistula occurring formation after diversion techniques like pancreatico-enterostomy. Pancreatic duct obliteration is applicable after all sorts of partial pancreatic resections, pancreas transplantation included. Although the method is safe, experiments have shown that not only complete exocrine atrophy is induced, but that also the endocrine architecture is destroyed. In dogs, the destruction of islet architecture leads to about 70% reduction of the insulin secreting capacity. It is not known whether such a severe reduction of endocrine function also occurs after pancreatic duct obliteration in man. This would discard duct obliteration as a procedure suitable for pancreas transplantation, since optimal endocrine pancreas function is the aim of pancreas transplantation in patients suffering from type-I diabetes mellitus.

Animals↗

A model for direct and quantitative assessment of pancreatic hormone secretion.

The usual parameters for the assessment of pancreatic endocrine function are oral or intravenous tolerance tests with various kinds of stimuli, generally glucose. Such tests provide information as to the pancreatic endocrine capacity in an indirect fashion, and the actual hormone output cannot be readily determined. The results are presented of a model in dogs with which the hormone producing capacity of the left lobe of the pancreas can be quantitatively assessed directly. The complete and undiluted venous blood from the left pancreatic lobe is sampled by cannulation of the splenic and the portal vein, under general anaesthesia. Removal of the right lobe is obligatory. With this model pancreatic blood flow, hormone secretion, and oxygen consumption can be studied after different sorts of stimuli. Moreover there is opportunity to determine the effect of various manipulations of the pancreas on its hormone secreting capacity directly.

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Pancreas transplantation in The Netherlands: report of the first case.

This case report describes the first clinical pancreas transplant performed in The Netherlands. A duct-obliterated segmental graft from a cadaver donor was transplanted to a male recipient who was insulin-dependent after total pancreatectomy eight years earlier. The recipient was off insulin for four postoperative months; during this period a rejection crisis was successfully treated. The graft was removed eight months after transplantation. Histologic examination indicated both fibrosis and rejection to have presumably contributed to graft failure. The patient is well but again insulin-dependent.

Chronic Disease↗

The effects of duct obliteration and of autotransplantation on the endocrine function of canine pancreatic segments.

This study in dogs addresses itself to the endocrine function of the duct-obliterated left pancreatic lobe (body and tail), which is the portion of the pancreas used for segmental transplantation. The endocrine function was determined with intravenous (i.v.) glucose tolerance tests and expressed in K-values and insulin-response curves. Duct obliteration of the nontransplanted left lobe was associated with normal K-values in the presence of the unmodified right lobe, but with reduced K-values in its absence. Removal of the left lobe while leaving the right lobe untouched was not associated with reduced K-values, but duct obliteration of the whole pancreas was. When the duct-obliterated left lobe was transplanted onto the iliac vessels (segmental autografts), K-values were reduced when compared with the unmodified situation, but were significantly higher than with nontransplanted, duct-obliterated left lobes. Insulin-response curves of nontransplanted, duct-obliterated segments differed both qualitatively and quantitatively from the unmodified situation, but insulin-response curves of duct-obliterated segmental autografts showed only qualitative differences with the unmodified situation. It is concluded that duct obliteration rather than the absence of the right lobe is the predominant cause of reduced glucose tolerance with duct-obliterated left pancreatic lobes. It is suggested that duct obliteration affects the endocrine pancreas both in a qualitative and quantitative fashion. The qualitative effect is similarly demonstrable with segmental autografts and nontransplanted segments, but the quantitative effect is largely dissolved with autografting by virtue of caval as opposed to portal venous drainage.

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The effect of duct obliteration on the histology and endocrine function of the canine pancreas.

Although duct obliteration is a safe and effective method for ablation of exocrine secretion in segmental pancreas transplantation, it remains to be clarified whether its effects are restricted to the exocrine tissue. In 20 dogs (beagles 9-15 kg) the right lobe of the pancreas was removed and the ductal system of the left lobe was injected with the duct-obliterants neoprene (6 dogs), polyisoprene (6 dogs), or prolamine (8 dogs). In this study, i.v. glucose tolerance tests (the results of which are expressed in K values) and relaparotomies for taking biopsies were performed at 1, 3, and 12 months after duct obliteration. Biopsies were studied histologically and immunohistochemically in a qualitative and semiquantitative fashion. Three prolamine-injected dogs developed diabetes. All other dogs maintained normal fasting blood glucose levels but showed reduced K values at 1 month after duct obliteration. Further deterioration of glucose tolerance was not observed up to 12 months. Differences in K values depending on the type of obliterant were insignificant at all intervals. The exocrine tissue was completely replaced by fibrosis at 3 months after duct obliteration, and the architecture of the islets was disrupted. Morphometrical analysis of relative numbers of different endocrine cell types showed transient changes at 1 month after duct obliteration, but did not differ from unmodified controls at 12 months. We conclude that the effects of duct obliteration are not restricted to the exocrine pancreatic tissue, but that the endocrine pancreas is interfered with as well. Changes in islet function and histology are brought about during the first month after duct obliteration and stabilize thereafter.

Animals↗

Arterial blood supply of the left lobe of the canine pancreas. II. Electromagnetic flow measurements.

The arterial blood flow through the left lobe of the canine pancreas was assessed by means of electromagnetic flow measurements under three different experimental conditions. First, flow was measured in 14 unmodified left pancreatic segments. The mean segmental blood flow was 9.1 +/- 4.5 ml/min, while the mean blood flow through the splenic artery was 53.3 +/- 21.2 ml/min. Next, flow was measured in seven of these dogs 1/2 hour after occlusion of the ductal system and construction of an end-to-end arteriovenous fistula between the distal splenic vessels. The segmental pancreatic blood flow remained unchanged, and the blood flow in the splenic artery increased more than twofold. Third, flow was measured in seven dogs (eight measurements) at 3 to 8 months after ductal occlusion of the left lobe. No significant decrease in segmental pancreatic blood flow was demonstrable up to 8 months. It is concluded that the arterial blood flow through the left lobe of the canine pancreas amounts to less than 20% of that in the splenic artery, that an end-to-end arteriovenous fistula increases the blood flow through the splenic artery and thus may contribute to the prevention of vascular thrombosis, and that the eventual decrease of endocrine function or occurrence of vascular thrombosis in duct-obliterated pancreatic grafts cannot be readily explained by a reduced blood flow as a consequence of either duct obliteration as such or fibrosis induced by duct obliteration.

Animals↗

Arterial blood supply of the left lobe of the canine pancreas. I. Anatomic variations relevant to segmental transplantation.

The anatomy of the arterial blood supply of the left lobe of the pancreas was studied in 70 beagles. It was found to be supplied by one small artery only, which was called the pancreatic artery. The pancreatic artery originated from the splenic artery (type I) in 56 dogs (80%). However, it originated from the cranial mesenteric artery (type II) in 14 dogs (20%). In the presence of type I anatomy, the surgical technique for segmental pancreatic transplantation can, in general, be performed in a routine fashion. In the presence of type II anatomy, a modification should be applied. This modification is described and illustrated. It is concluded that the pancreatic artery should always be identified at operation, and that the specific surgical procedure chosen should depend upon the anatomy found. In addition, ischemic necrosis of segmental pancreatic grafts can only be explained by vascular thrombosis if the pancreatic artery has been recognized and preserved with certainty at transplantation.

Animals↗

The persisting capability for vasodilatation in duct-occluded canine pancreatic segments.

The effect of duct-obliteration and duct-obliteration induced fibrosis on the capability for vasodilatation of the pancreatic vasculature was investigated in dogs. It was demonstrated that the increase of basal blood flow through left pancreatic segments, induced by intra-arterial injection of papaverin, remained unchanged during 6 months after duct-obliteration. It is concluded that impairment of endocrine function of duct-obliterated segmental pancreatic grafts cannot be readily explained by a functional impairment of the pancreatic vessels.

Animals↗

The relationship between carcinoma of the rectum and hemorrhoids.

The suspected positive correlation between rectal carcinoma and hemorrhoids was examined in a retrospective study. In patients older than 50 a significant positive correlation could be demonstrated between rectal carcinoma and hemorrhoids. In the group of hemorrhoid patients described it could not be shown that rectal carcinoma was more frequent than in the normal population. In patients older than 40 with hemorrhoids a rectoscopy is always recommended. In this material the colonic enema did not contribute any diagnostic information from which therapeutic consequences could be inferred.

Adult↗

Added value of CT criteria compared to the clinical SAP score in patients with acute pancreatitis.

BACKGROUND: To assess the added value of established computed tomography (CT) scores versus the Simplified Acute Physiology (SAP) score in predicting outcome in patients with acute pancreatitis. METHODS: Contrast-enhanced CT was performed in 45 patients with acute pancreatitis. The Balthazar score, CT severity index (CTSI), and Schröder score were assessed, and the SAP score was calculated. The predictive values of CT score and SAP score for mortality, need for one or more interventions, and length of hospital stay were compared. The added value of the SAP score to the CT scores was assessed by using ROC (receiver operating curve) analysis. RESULTS: The positive predictive values of the higher Balthazar, CTSI, Schröder, and SAP scores, reflecting severe disease, were 50%, 41%, 41%, and 48%, respectively, for mortality, 85%, 84%, 84%, and 83%, respectively, for need for one or more interventions, and 55%, 66%, 66%, and 65%, respectively, for longer hospital stay. The negative predictive values of the lower Balthazar, CTSI, Schröder and SAP scores were 84%, 92%, 92%, and 42%, respectively, for mortality, 44%, 69%, 69%, and 45%, respectively, for need for one or more interventions, and 44%, 69%, 69%, and 55%, respectively, for longer hospital stay. When CT scores were added to the SAP score, there was no improvement in discriminating power for mortality. CONCLUSION: To identify patients with severe outcome, there is no clear benefit using established CT scores as opposed to the SAP score. However, the Balthazar score and CTSI are better than the SAP score in predicting a favorable outcome.

Adult↗

Assessment of islet isolation efficacy in dogs.

The outcome of islet isolation is considered uncertain because of the large variability of islet and insulin yield, but comparison of the isolated and native islet population has not been attempted. We therefore addressed the efficacy of collagenase digestion, and density gradient purification of islets from the splenic dog pancreas (n = 31) by morphometry of the islet volume and size distribution, and by extraction of insulin and amylase, in samples from the pancreas, the digest, and gradient fractions. In contrast to a approximately 90% recovery of pancreatic insulin and amylase after digestion, islet yield amounted to 50% of the islet content of the pancreas. After density separation, islets were mainly found in the purified fractions, while half of the recovered insulin was located in the acinar fraction of the gradients-indicating a substantial proportion of islets entrapped in acinar fragments. The islet and insulin content of the pancreas correlated well with islet and insulin yield after digestion (r = 0.7, p < .0001). The insulin content of digest suspensions did neither correlate with islet nor insulin recovery in the purified fraction of the gradients (r = 0.4) as opposed to the islet content of digest suspensions, which correlated with both (r = 0.7, p < .0001). After density separation near 100% purity was obtained, and no loss of insulin from isolated islets was demonstrated by extraction and microscopy. Size distributions of native and isolated islets demonstrated no fragmentation. We conclude that the variability of isolation outcome may be attributed to a large extent to the variability of the native endocrine pancreas. Isolation efficacy was best documented by morphometry, because insulin extraction did not discriminate between free and entrapped islets. However, assessment by both morphometry and extraction allowed the quantitation of entrapped islets, and demonstrated preservation of beta-cell granulation. Similar studies should facilitate the analysis of other factors affecting islet isolation in man.

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