Summary.Pancreatic tissue obtained at subtotal pancreatectomy from 15 infants with persistent hypoglycaemia with hyperinsulinism, and autopsy specimens from 23 age-matched normoglycaemic controls, were studied with morphometric methods after immunocytochemical staining of the four main islet cell types (A, B, D and pancreatic polypeptide cells). In three cases, a focal lesion was detected by gross examination. Macroscopic or microscopic examination did not distinguish the 12 other cases from controls. As found previously, nesidioblastosis was not a specific feature of the pancreas in infantile hypoglycaemia, being observed in age-matched controls as well. In cases with hypoglycaemia the volume density of B cells was not significantly increased; that of the A cells was within normal range. The volume density of pancreatic polypeptide cells was markedly augmented and that of somatostatin cells was significantly decreased. The mean nuclear volume of the B cells was increased by 40% in cases with diffuse changes, but in cases with a focal lesion this increase was restricted to the abnormal area. This finding is of decisive importance for diagnosis and has therapeutic implications. The increase in B-cell nuclear size is thought to reflect an enhanced functional activity of these cells. On the other hand, the figures obtained for the volume density of B and D cells must be viewed with some reservation because degranulation may interfere with accurate detection of these cells.Key words: Persistent hypoglycaemia, nesidioblastosis, islet cells, islet adenoma, immunocytochemistry. Thirty years after its initial description by McQuarrie[1], the syndrome of persistent neonatal hypoglycaemia with hyperinsulinism still remains poorly understood. Nesidioblastosis [2], i.e. diffuse and disseminated proliferation of islet cells budding off from ducts, has been repeatedly proposed as the underlying pathological lesion in the pancreas [3][4][5][6][7][8][9][10][11]. As a consequence of this proliferation, an increase in the mass of insulin cells was proposed to be the morphological antecedent of the hyperinsulinism [12]. Recent observations based on quantitative immunohistochemical investigations have shown, however, that nesidioblastosis is a common feature of the pancreas in normal neonates and infants [13-181.The concept of nesidioblastosis as the structural lesion underlying persistent neonatal hypoglycaemia with hyperinsulinism has thus been questioned and other aetiologies have been proposed. Thus, a decrease of somatostatin-containing cells was detected in several cases by quantitative histological/histochemical [18] and immunohistochemical [19][20][21][22] analyses of the endocrine pancreas and was corroborated by radioimmunoassay measurements of a low concentration of somatostatin in extracts of whole pancreas [20]. Other reported abnormalities are the loss of centrilobular aggregation of the endocrine cells, and the existence of small clusters of endocrine parenchymal cells throughout the exocrine tissue associated with a...
The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.
SUMMARY An experimental model was used which includes intragastric instillation of 80 mM HCI and 0O6 ml bile/kg followed by intravenous infusion of live E coli in cats for up to three hours. This procedure regularly induces gastric mucosal ulcerations. Mucosal blood flow was measured by microspheres before, early, and late in sepsis. Total gastric blood flow was recorded electromagnetically. Mucosal regeneration capacity as reflected by the RNA/DNA ratio was measured. Misoprostol (a PGE1 analogue) was infused iv (5 ,g/kgxh) or given locally in the stomach (10 ug/kg) before bacteriemia. Misoprostol did not influence the haemodynamic response to bacteria. The gastric mucosal damage was assessed either as an index representative for the entire corpus-fundus region or as the number of areas with intact surface epithelium within the series. Misoprostol iv protected the mucosa from ulceration compared with untreated septic controls while misoprostol intragastrically significantly reduced the number of damaged areas only. Topical misoprostol increased total gastric and mucosal blood flows early in sepsis compared to iv or no pretreatment while no difference was seen during late sepsis. The protective effect of misoprostol was thus not dependent on increased gastric mucosal blood flow. Nor was it mediated through effects on mucosal nucleic acid concentrations or ratio.Prostaglandins in doses that have no effect on acid production protect the gastric mucosa from damage caused by stress of various kinds. This 'cytoprotective' effect' has been well documented in several studies during the last two decades.2 3 The mechanism underlying the cytoprotective effect of prostaglandins, however, remains unclear.Acute gastric mucosal damage (stress ulcer) is a potentially dangerous complication in septicaemia.4 5 Cytoprotective agents might be of importance in the prevention of the development of these lesions. Misoprostol, a novel PGE1 analogue (G D Searle Co Ltd, USA) has been found to have gastric antisecretory and cytoprotective prop-6 7 erties. septic shock model and to relate this cytoprotective effect, if any, to effects on regional blood flow, mucosal regeneration capacity, and central haemodynamics. Methods CATSThe experiments were carried out on 20 cats, weighing 1-9-4-7 kg. They were deprived of food for 24 hours with free access to water. Anaesthesia was induced by approximately 50 mg pentobarbital iv (Pentothalg) and continued with chloralose (50 mg/kg bw).Operative procedures, determination of gastric mucosal blood flow, histologic examination and biochemical analysis have been previously described in detail.8 Briefly, the animals were tracheotomised and ventilated artificially. A thoracotomy was done to allow injection of radioactively labelled microspheres in the left atrium. A Swan-Ganz catheter
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.