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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite widespread evidence that autoimmune mechanisms may contribute to the beta cell necrosis associated with type I insulin-dependent diabetes mellitus (IDDM), it has not heretofore been demonstrated that islet cell antibodies (ICAs), directed primarily against cytoplasmic antigens, are capable of specific lysis of beta cells. We utilized a readily accessible source of mouse pancreatic islets [CBA/J mice lacking exocrine pancreas (exocrine pancreatic insufficiency syndrome)] to experimentally induce ICAs inbred mice. Homogenates of these islets were injected weekly for four weeks into syngeneic (CBA/J) and allogeneic (A/J, C57BL/6J, C57BL/KsJ) recipients. Only C57BL/KsJ inbred mice showed the induction of a high titer (greater than or equal to 160) antiserum cytotoxic to 51Cr-labeled CBA/J lymph node target cells. Neither the immunized C57BL/sJ mice with circulating ICAs nor any of the other immunized strains showed any decrease in glucose tolerance as compared with vehicle controls. Moreover, no morphologic evidence of islet necrosis or atrophy was apparent. Thus the ICAs induced were reactive with alloantigenic determinants of the donor and unreactive with antigenic determinants of the recipient strain. The C57BL/KsJ antiserum was further screened for anti-islet cell cytotoxic activity using both a 51Cr release assay from CBA/J islet cell monolayer cultures, and immunocytochemical staining of sections of Bouin's fixed, paraffin-embedded pancreas. This antiserum was cytotoxic to CBA/J beta cells in monolayer culture, but not the other non-beta islet cell types. Immune lysis of the beta cell required rabbit complement. At a concentration of 1% antiserum and 4% complement, beta cell lysis was evident between 3 and 4 h at 37 degrees C. Ultrastructural examination of beta cells exhibiting cytopathic changes revealed cytoplasmic disarray rather than any obvious lytic events at the plasma membrane. Grossly distended, rough, endoplasmic reticulum containing intracisternal type A retrovirus was the most prominent feature distinguishing antiserum and control serum-treated beta cells. This model system suggests that ICAs which recognize beta cell cytoplasmic antigens are capable of specifically lysing beta cells via a complement-dependent mechanism. Immunocytochemical staining revealed that, in addition to islet beta-cells,, the antiserum (1/500 dilution) stained a macrophage-like cell in the spleen and lymph nodes, as well as an epithelial-like cell in the thymus. The possibility is discussed that this multiple specificity may have been due to passenger leukocytes present in the islet homogenates used to immunize.
Diabetes 1981 Jan
PMID:Induction in C57BL/KsJ mice of complement-dependent antibody cytotoxic to cultured beta cells. 701 3

Ten patients, all with intractable pain due to chronic pancreatitis, were selected for treatment by lateral pancreaticojejunostomy (modified Puestow procedure) after preoperative endoscopic pancreatography in each had revealed dilatation of the main pancreatic duct. Follow-up endoscopic pancreatograms performed 1 yr after surgery show a patent anastomosis in all 10 patients. Eight of these 10 are largely or completely pain-free, but 2 continiue to have pain without improvement after the operation. Surgical success in relieving pain was accompanied neither by improvement in pancreatic function, nor by protection against its further deterioration: Whereas 2 patients had malabsorption and 3 were diabetic preoperatively, 6 had malabsorption and 5 had diabetes postoperatively. This progression of exocrine or endorine pancreatic insufficiency indicates that decompression of the dilated pancreatic duct, although an effective means for relief of pain in chronic pancreatitis, does not prevent continuing destruction of pancreatic glandular tissue.
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PMID:Long-term patency, pancreatic function, and pain relief after lateral pancreaticojejunostomy for chronic pancreatitis. 739 32

21 patients (10 male, 11 female) aged between 11 months and 29 years with Shwachman's syndrome are reviewed. All patients had exocrine pancreatic insufficiency. Haematological features included neutropenia in 19 (95%), anaemia in 10 (50%), and thrombocytopenia in 14 (70%); one patient developed erythroleukaemia. Severe infections occurred in 17 (85%) from which 3 (15%) died. Only one child exceeded the 3rd centile for height, and growth retardation was particularly evident in the older patients. All had skeletal abnormalities or delayed skeletal maturation, or both. Metaphyseal dyschondroplasia affected 13 of the older patients and was associated with skeletal deformities. Eight of 9 children under 2 1/2 years had rib abnormalities. Respiratory function tests in children under 2 years demonstrated reduced thoracic gas volume and chest wall compliance. Older patients had reduced forced expiratory volume and forced vital capacity. Neurological assessment showed developmental retardation or reduced IQ assessments, or both, in 85% of patients studied. Other neurological abnormalities included hypotonia, deafness, and retinitis pigmentosa. Neonatal problems had been present in 16 (80%) of the patients and 5 were of low birthweights. Hepatomegaly with biochemical evidence of liver involvement occurred in the younger patients and resolved with age. Other associated features included dental abnormalities, renal dysfunction, an icthyotic maculopapular rash in 13 (65%), delayed puberty, diabetes mellitus, and various dysmorphic features. These findings stress the diverse manifestations of the syndrome and extend knowledge on a number of aspects. Sibship segregation ratios support an autosomal mode of inheritance and an hypothesis for the pathophysiological basis of this syndrome is advanced.
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PMID:Shwachman's syndrome. A review of 21 cases. 743 69

Diarrhoea in patients with diabetes mellitus may be due to anorectal or rectal dysfunction that results in incontinence, intestinal secretion or rapid intestinal transit, or may be associated with disorders that typically cause malabsorption. The latter include small bowel bacterial overgrowth, coeliac sprue and pancreatic insufficiency. A practical algorithm for diagnosis and advances in therapy is discussed.
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PMID:Diarrhoea in patients with diabetes mellitus. 749 59

The frequency of acute or chronic pancreatitis in primary hyperparathyroidism has decreased from the former 5-10% to 1-2% thanks to earlier diagnosis and operative treatment. Chronic pancreatitis, which occurs only in prolonged primary hyperparathyroidism, should therefore virtually disappear. We investigated this topic in a prospective long term study of chronic pancreatitis (1963-1992). Over the last three decades 336 patients with chronic pancreatitis have been studied at regular intervals. 245 suffered from alcohol-induced (84% with calcifications) and 91 from non-alcohol-induced chronic pancreatitis (77% with calcifications). The average period of observation in the group with non-alcohol-induced chronic pancreatitis was 10.6 years. Primary hyperparathyroidism was found in 6 patients (4 male, 2 female), i.e. 6.6% of non-alcohol-induced chronic pancreatitis (100% with calcifications). They were evenly distributed over the 30 years' study period. 3 patients had acute attacks of pancreatitis prior to the diagnosis of chronic calcific pancreatitis (2 months, 3 + 8 years). In 3 patients with primary painless chronic calcific pancreatitis the condition was diagnosed twice incidentally and once because of diabetes mellitus. Chronic pancreatitis was diagnosed 3 times before primary hyperparathyroidism (8.3 +/- 2.1 years), once simultaneously and twice afterwards (2 + 14 years). In three patients chronic pancreatitis was initially misinterpreted as alcohol-induced. Severe exocrine pancreatic insufficiency was present in 4 of 5 patients (no data in one), and diabetes mellitus in 3 of 6 patients. At the time of diagnosis of primary hyperparathyroidism, mean serum calcium was 3.08 +/- 0.43 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chronic pancreatitis and primary hyperparathyroidism]. 807 34

Intraoperative electron beam radiotherapy (IORT) is clinically used as a potential adjunctive treatment to surgery of locally advanced pancreatic and gastric cancer. The tolerance of the pancreas to IORT was studied in 15 adult beagles, divided in 3 groups of 5 beagles in which 25, 30 or 35 Gy IORT was delivered through a 6-7 cm circular lucite cone with 6-8 MeV electrons to the pancreas and medial wall of the duodenum. The dogs were followed for endocrine and exocrine pancreatic insufficiency. Two dogs (13%) developed radiation-induced morbidity which consisted of a common bile duct stenosis and an enterocolic fistula, as was confirmed at autopsy after 8 and 18 months, respectively. After a follow-up of 1 year, none of the dogs had developed pancreatitis, diabetes or exocrine insufficiency. There was a significant reduction in serum insulin levels and glucose clearance rates without overt diabetes for 30 Gy and 35 Gy (p < 0.05). No significant changes were found for 25 Gy. This study suggests that 25 Gy IORT to the pancreas may be used clinically, and that higher IORT doses may induce endocrine pancreatic insufficiency in the long-term.
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PMID:Intraoperative irradiation of the canine pancreas: short-term effects. 812 87

Pancreatic transplantation for endocrine replacement is well-established for insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas transplantation has been maintained after orthotopic cluster transplants for malignancy, and restoration of adequate exocrine function in a previously deficient patient has been reported in a patient with chronic pancreatitis who developed labile diabetes and steatorrhea after pancreatectomy. We performed a triple organ transplant (pancreas, liver and kidney) in a patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to cystic fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine secretions were drained enterically to the jejunum. At 24-month follow-up, malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are normal. Serum carotene is within the normal range. Exocrine pancreatic insufficiency in CF patients can be corrected by pancreas transplantation. However, routine use in CF is precluded by the risks of surgery and immunosuppression. For diabetic patients with pancreatic exocrine insufficiency who require another organ transplant (e.g., lung, liver, or kidney), simultaneous pancreas transplantation with the exocrine secretions directed into the upper gastrointestinal tract should be considered.
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PMID:Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient. 813 59

A 21-year-old female with autoimmune polyglandular failure (APG) manifested by insulin-dependent diabetes mellitus (IDDM), hypothyroidism and pernicious anaemia developed severe malabsorption due to exocrine pancreatic insufficiency. Supplemental pancreatic enzymes resulted in marked improvement of steatorrhea. There was also an incidental finding of gastric carcinoid tumour. We identified only 13 other patients in our institution with either type 2 or 3 APG, one of which had significant steatorrhoea. Another patient with IDDM, hypothyroidism and pernicious anaemia had an asymptomatic gastric carcinoid tumour. The possible mechanisms for malabsorption in APG are discussed.
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PMID:Autoimmune polyglandular failure associated with malabsorption and gastric carcinoid tumour. 825 57

We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis.
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PMID:Idiopathic chronic calcifying pancreatitis with diabetes mellitus. Analysis of pancreatic stone protein gene. 848 98

Free radicals have been suspected to play a role in the pathogenicity of alcohol-related chronic pancreatitis. The aim of this study was to determine the status of several antioxidant parameters in these patients and examine the factors that are likely to influence them. Thirty-five subjects (23 males and 12 females, mean age 48 +/- 8 years) with disease proven by endoscopic pancreatography and 14 healthy controls (6 males and 8 females, mean age 44 +/- 7 years) were included in the study. Biochemical antioxidant parameters included: selenium, zinc, and copper levels in plasma; glutathione peroxidase in plasma and erythrocytes; plasma malondialdehyde concentrations assessed by thiobarbituric acid reactants; and serum vitamin E and A levels. Selenium and vitamin E oral intake was assessed by a five-day diet analysis. Hemoglobin (130 +/- 16 vs 143 +/- 15 g/liter), vitamin E (8 +/- 5 vs 16 +/- 9 mg/liter), vitamin A (30 +/- 11 vs 49 +/- 12 micrograms/dl), selenium (54 +/- 20 vs 87 +/- 11 micrograms/liter), and plasma glutathione peroxidase (903 +/- 313 vs 1326 +/- 168 units/liter) were significantly lower in patients than in controls (P < 0.05). In contrast, white blood cell count, C-reactive protein, and plasma copper levels were significantly higher in patients than in controls. Cholesterol, triglycerides, iron, ferritin, total proteins, zinc, and malondialdehyde were not different. Vitamin E was lower in patients with steatorrhea, while vitamin A was lower in patients with concomitant diabetes mellitus. Dietary intakes were not different between patients and controls. In conclusion, patients with alcohol-related chronic pancreatitis have low blood levels in many antioxidant factors. Dietary intakes of some of them (selenium and vitamin E) are adequate, however. Such deficiencies are secondary to pancreatic insufficiency and probably to increased requirements related to enhanced oxidative stress.
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PMID:Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis. 865 56


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