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  • 1
    ISSN: 1432-0428
    Keywords: Kidney size ; diabetic nephropathy ; creatinine clearance ; mesangium ; glomerular basement membrane ; urinary albumin excretion ; hypertension ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-five patients with Type 1 (insulin-dependent) diabetes mellitus and 90 normal subjects had renal size (renal area index) determined by X-ray and also had examination of renal biopsies by light and electron microscopy. Renal area index of 206±32 cm2/1.73 m2 (mean±SD) in the Type 1 diabetic patients exceeded that in the normal subjects (180±25 cm2/1.73 m2, p〈0.001). In the diabetic patients, the renal area index correlated with creatinine clearance (r=+0.43, p〈0.05), but did not correlate with urinary albumin excretion, or the electron microscopic measurements of percentage total mesangium and glomerular basement membrane width. In diabetic patients with clinical nephropathy or severe glomerulopathy on biopsy, the kidneys may remain large. Thus, renal size does not indicate the severity of diabetic renal lesions on biopsy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 267-281 
    ISSN: 1432-0428
    Keywords: Diabetic glomerulosclerosis ; dialysis ; kidney transplantation ; conservative treatment ; diabetes mellitus ; diabetic complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Keywords Islet cell ; antigen ; autoimmunity ; autoantibody.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87 % of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3–19 %). Sera from 41.9 % of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6 % of parents and 37.9 % of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85 %) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2. [Diabetologia (1996) 39: 1365–1371]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Genetics ; Type 2 (non-insulin-dependent) diabetes mellitus ; HLA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidemiologic data suggest that a parental history of Type 2 (non-insulin-dependent) diabetes mellitus increases the risk of Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 and Type 2 diabetes. We have previously reported evidence that HLA-DR4-linked factors may represent a homogeneous subset of diabetes susceptibility. First, HLA-DR4 frequency was higher in Type 1 diabetic study subjects with a Type 2 diabetic parent than in Type 1 diabetic subjects whose parents were not diabetic. Second, a DR4-haplotype was transmitted from the Type 2 diabetic parent to the Type 1 offspring more often than expected. These data are consistent with the hypothesis that families with a Type 2 diabetic parent and Type 1 diabetic child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility. In this report, we further explore the relationship between the high-risk HLA antigen (HLA-DR4) in study subjects with differing glycaemic status (National Diabetes Data Group criteria). In this community-based study, we find evidence that HLA-DR4 is increased in study subjects with Type 2 diabetes and may be a marker for Type 2 diabetes susceptibility.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Genetics ; Type 1 (insulin-dependent) diabetes mellitus ; Type 2 (non-insulin-dependent) diabetes mellitus ; HLA ; haptoglobin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidemiologic data suggest that having a parent with Type 2 (non-insulin-dependent) diabetes mellitus increases the risk for Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 diabetes and Type 2 diabetes. We contrast genetic risk factors in three sets of families, consisting of (1) a single Type 1 diabetic child (proband) and non-diabetic parents, (2) multiple Type 1 diabetic siblings and non-diabetic parents, and (3) at least one Type 1 diabetic child and at least one Type 2 diabetic parent. Previous studies have demonstrated that HLA region genes, which elevate the risk in Type 1 diabetes, have no significant effect with respect to the risk for developing Type 2 diabetes. An earlier report cited a contribution by the haptoglobin locus to genetic susceptibility for Type 2 diabetes. We provide evidence that a high risk HLA antigen (HLA-DR3) is decreased to a greater extent in Type 1 patients with a Type 2 parent than in Type 1 patients in which the parents are not diabetic. The role of HLA-DR4 is maintained in these families, with an unexpectedly significant increased rate of transmission of the HLA-DR4 allele from Type 2 parent to Type 1 offspring. The role of haptoglobin in these families does not appear to be important, either with respect to association with diabetes or with respect to linkage with a secondary susceptibility locus. These results indicate that families with a Type 2 parent and Type 1 child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; glomerulosclerosis ; light microscopy ; University Group Diabetes Program ; hyperglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kidney tissue of acceptable quality was available from autopsies of 55 patients who had been followed prospectively for 3 to 15 years as participants in the University Group Diabetes Program, a study of vascular disease in Type 2 (non-insulin-dependent) diabetic patients. Slides were prepared for light microscopic reading by uniform histologic techniques, and then were randomly intermixed and coded with tissues identically prepared from matched nondiabetic subjects (morphologic controls). After independent review by three morphologists, the results were tabulated and assigned to one of four diagnostic groups: 1) typical diabetic nodular glomerulosclerosis; 2) mesangial changes suggestive of diabetes (diffuse lesion); 3) non-diabetic renal disease; 4) normal for age. Of the diabetic cases 31% (17 of 55) were found to show nodular glomerulosclerosis, and another 47% (26 of 55) showed suggestive changes; none of the morphologic control slides was read as showing nodular glomerulosclerosis, but some were judged to show suggestive mesangial (diffuse) changes. Although only 4 of the 17 diabetic patients with nodules had died of uraemia, many had hypertension, which may have contributed to their deaths from vascular disease. The patients with nodular glomerular changes also showed, on the average, the highest blood glucose levels during life. Type 2 diabetes in later life appears to be associated with a high risk for typical tissue changes of diabetic kidney damage, which may contribute significantly to morbidity and mortality and may be present before azotaemia and qualitative proteinuria have been recognized.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have developed a technique for allotransplantation of the pancreas in pancreatectomized dogs. This method employs a graft of the whole pancreas and duodenum (P-D) which is placed in a heterotopic position with drainage of exocrine secretions of the grafted pancreas into the recipients jejunum via the graft duodenum. Venous return from the P-D allograft is directed into the systemic rather than the portal venous system. Panereatectomized dogs with such P-D allogrâfts have survived many months if immunosuppressive drugs are given to prevent rejection. We have also found that the P-D graft can survive in vitro without circulation and retain the ability to secrete insulin when stimulated by blood glucose perfusion after as long as 24 h of in vitro preservation. Preservation is done with a chamber which combines hypothermia to 5 °C and hyperbaria to 4 atmospheres of oxygen. Armed with this knowledge, we have made P-D allografts combined with renal allografts in five patients with insulin dependent, juvenile onset diabetes mellitus with terminal nephropathy. Two of these patients have left the hospital and have normal function of the P-D and renal allografts. Neither patients has required insulin since transplantation, 11 months and 7 months ago. P-D allotransplantation is now planned for insulin dependent, juvenile onset diabetics who have significant but not terminal nephropathy or retinopathy. If P-D allotransplantation is found to slow, cause to regress, or prevent the vascular deterioration characteristic of diabetes mellitus, then it may become the most frequent organ transplant because of the increasing incidence of diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 27 (1984), S. 149-153 
    ISSN: 1432-0428
    Keywords: Pancreas transplant ; cyclosporin ; azathioprine ; HLA-identical siblings ; glucose metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Of 89 pancreas transplants performed in 77 diabetic patients (43 with and 34 without previous kidney transplants), 53 were from cadaver and 36 from related donors. To date, 64 patients (83%) are alive and 27 (35%) have functioning grafts (14 〉 1 year), including 0 out of 3 duct-ligated, 3 out of 15 open-duct, 17 out of 32 enteric-drained, and 7 out of 39 duct-injected. Of technically successful allografts, 8 out of 16 (50%) in the azathioprine- and 17 out of 47 (36%) in the cyclosporin-treated recipients are functioning (eight cyclosporin patients also take azathioprine). Seven of the nine (78%) non-kidney-transplant recipients of technically successful pancreas allografts from HLA-identical siblings have functioning grafts. Causes of graft failure include allograft rejection, fibrosis secondary to duct injection, or selective β-cell destruction independent of rejection. Of the 24 recipients who are currently insulin-independent, 14 have normal or near-normal glucose tolerance test results, while 10 have abnormal results, even though they are otherwise euglycaemic. The patient population to whom pancreas transplantation is applied is gradually changing, and non-uraemic, non-kidney-transplant patients currently comprise the majority of our cases (17 out of 24 in 1983; nine of the 17 currently have functioning grafts). We now prefer the enteric drainage technique. Except for recipients of related grafts from a previous kidney donor, in which case it is necessary only to continue the current immunosuppressive regimen, we now administer cyclosporin and prednisone for immunosuppression in recipients of HLA-identical sibling grafts, and cyclosporin, azathioprine and prednisone (triple therapy) for recipients of HLA-mismatched grafts. The most interesting features in this series of cases are the variable patterns of glucose metabolism post-transplant, the finding that processes other than graft rejection, may lead to loss of β-cell function, preliminary observations on changes in morphology of kidneys following restoration of normoglycaemia, and the evolution of an immunosuppressive regimen that appears to prevent allograft rejection in non-uraemic, non-kidney-transplant patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-5233
    Keywords: Fasting plasma glucose ; Diabetes mellitus Epidemiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In current clinical and research practice, the determination of diabetic status depends largely on plasma glucose levels 2 h after the ingestion of a standard 75-g glucose load, the oral glucose tolerance test (OGTT). The OGTT, however, remains inconvenient, not highly reproducible, and costly, especially for large-scale studies and population screening tests. Fasting plasma glucose (FPG) determinations are convenient, reliable, and valid measures of glucose intolerance, but the currently prescribed cut-off point of 140 mg/dl (7.8 mM) lacks sensitivity. We evaluated the reliability and validity of fasting plasma glucose (FPG) values compared with other measures of hyperglycemia for a diagnosis of diabetes in a populationbased study of carbohydrate metabolism in Wadena, Minnesota, a community of predominantly northern European ancestry. As a part of this effort, a random sample of Wadena adults, stratified by age and gender, plus all known, previously diagnosed diabetics participated in 2 days of baseline testing and were followed prospectively and retested 5 years later. Cross-sectional analyses of baseline data are presented in this article. Diabetic status was ascertained by administering a standard OGTT according to National Diabetes Data Group (NDDG) specifications. Sensitivity and specificity levels obtained when using a FPG cut-off point of 6.4 mM were 95.2% and 97.4%, respectively. In study subjects with no known diagnosis of diabetes, the FPG cut-off point of 6.4 mM performed reasonably well with a sensitivity and specificity of 67.7% and 97.4%, respectively. A receiver operating characteristic (ROC) curve analysis showed that FPG consistently performed better than glycosylated hemoglobin in distinguishing diabetic from non-diabetic subjects. FPG concentrations accurately and reliably discriminate diabetic from non-diabetic individuals in a population-based study of Caucasians of northern European ancestry.
    Type of Medium: Electronic Resource
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