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E Standl

Publications and source records attributed to E Standl.

At least 19 recordsLinked to original sources

Involvement of dendritic cells in early insulitis of BB rats.

In this study, subsets of mononuclear infiltrates in pancreatic islets of BB rats at different stages of insulitis were determined by various monoclonal antibodies against rat lymphoid cells, including a mouse monoclonal IgM antibody that distinguishes between macrophages and dendritic cells (mAb 1F119). 1F119+ dendritic cells were absent in and around islets of Wistar control rats. In BB rats, the first alteration of islets detectable by immunohistochemistry when compared with normal islets was the enhanced expression of 1F119 antigen around and in the islets (17% 1F119+ islets). At disease stage 1 (i.e. no leukocyte infiltration after HE staining), lymphocytes and macrophages were almost absent. At disease stage 2 (leukocyte infiltration < 20 cells), a more intense form of dendritic cell infiltration was seen (stage 1 versus stage 2, P < 0.0001). In addition, ED2+ and ED3+ cells were present around the islets (50% of islets were infiltrated with 1F119+ cells versus 16% with ED2+, 19% with ED3+, 11% with W3/25+ cells, and 11% with OX8+ cells, P < 0.0001). At disease stage 3 (> 20 cells), a clear increase of ED2+ and ED3+ macrophages and of W3/25+ and OX8+ T-lymphocytes in the infiltrates was observed. These observations suggest a role for antigen presenting dendritic cells in the initiation of immune reaction in type 1 diabetes of BB rats.

Animals

[Clinical sequelae of hyperinsulinemia in diabetes mellitus].

Surprisingly enough, insulin has recently been suspected of promoting cardiovascular complications, provided it becomes effective in excess concentrations at the vascular walls. This applies to both endogenous hyperinsulinemia and insulin substitution performed exogenously with high insulin doses. Several large population studies in non-diabetics - carried out in Helsinki, Busselton and Paris - have proved recently that serum insulin concentration is an independent risk predictor for the occurrence of coronary heart disease. According to in vitro trials, insulin stimulates the proliferation of the smooth muscle cells in vascular media and the lipid synthesis, as well as lipid incorporation into the vascular wall. Very recent large-scale population studies in randomly selected type II diabetics (the Schwabing Study and one performed at Oxford) have revealed a close association between an endogenous insulin requirement, on the one hand, and the risk of macroangiopathy or coronary heart disease on the other.

Coronary Artery Disease

[Insulin autoantibodies and islet cell antibodies in recently appearing diabetes mellitus type I. Association with age of manifestation and HLA phenotype].

Insulin autoantibody (IAA) and islet cell antibody (ICA) titres were measured in 108 newly diagnosed type I diabetics (49 male, 59 female, mean age 20 [1-38] years) and 103 non-diabetic controls (41 male, 62 female, mean age 23 [16-46] years). IAA titres in the controls were normally distributed, with a mean of 5 +/- 11 nU/ml. The upper limit of normal was established as 49 nU/ml (mean + 4 standard deviations). Raised IAA and ICA titres were present in 45% and 44% of type I diabetics, respectively, with 59% positive for either IAA or ICA or both. IAA were markedly age-dependent, being positive in 70% (26 out of 37) of diabetics under the age of 15 years, and in 32% (23 out of 71) at the age of 15 years or more (P = 0.0004). There was a less marked difference for ICA titres (positive in 62% of patients less than 15 years, and in 35% of those of 15 years of older; P less than 0.01). IAA were significantly more common in HLA DR4 positive patients than in HLA DR4 negative patients (56% vs 11%; Pc less than 0.00015). With regard to age a significant association between IAA and HLA DR phenotype was present only in homozygous (Pc less than 0.03) and heterozygous (P less than 0.0003) patients aged 15 years or older. By contrast, ICA was not significantly correlated with HLA phenotype. These data suggest a genetic predisposition for the development of IAA.

Adolescent

[Insulin level--a parameter for risk of arteriosclerosis?].

Surprisingly enough, insulin has recently been suspected of promoting cardiovascular complications provided it becomes effective in excess concentrations at the vascular walls. This applies to both endogenous hyperinsulinemia and insulin substitution performed exogenously with high insulin doses. Several large population studies in non-diabetics--carried out in Helsinki, Busselton and Paris--proved recently that serum insulin concentration is an independent risk predictor for the occurrence of coronary heart disease. According to in-vitro trials, insulin stimulates the proliferation of the smooth muscle cells in vascular media and the lipid synthesis as well as lipid incorporation into the vascular wall. Very recent large-scale population studies in randomly selected type II-diabetics (the Schwabing Study and one performed at Oxford) have revealed a close association between endogenous hyperinsulinemia respectively high exogenous insulin requirement on the one hand and the risk of macroangiopathy or coronary heart disease on the other.

Arteriosclerosis

Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects.

In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.

Adolescent

HLA-associated insulin autoantibody formation in newly diagnosed type I diabetic patients.

To assess a possible HLA association with anti-insulin autoantibodies (IAAs) in human insulin-dependent (type I) diabetes, 51 newly diagnosed type I diabetic patients (mean age 22 +/- 8 yr) were typed for HLA-DR and HLA-DQ and studied for IAAs before exogenous insulin therapy with a competitive radioimmunoassay (normal range less than or equal to 49 nU/ml). The level of IAAs in 16 patients exceeded our upper limit of normal, and 18 had high-titer islet cell antibodies (ICAs; greater than or equal to 40 Juvenile Diabetes Foundation U). A striking association with HLA-DR4 (DQw3) in both the prevalence and the level of IAAs was found (IAA positivity in patients with DR4/4 vs. DR4 heterozygous vs. non-DR4: 90 vs. 29%, corrected [c] P less than 0.01, vs. 5%, Pc less than 0.0001; IAA positivity in patients with DR4 vs. non-DR4: 50 vs. 5%, Pc less than 0.005; IAA level in patients with DR4/4 vs. DR4 heterozygous vs. non-DR4: 111 vs. 17 nU/ml, Pc less than 0.01, vs. 20 nU/ml, Pc less than 0.0001; IAA level in patients with DR4 vs. non-DR4: 45 vs. 20 nU/ml, Pc less than 0.01). In contrast, none of the DR3+ subjects had IAAs above normal range, except in conjunction with DR4 (DR3 vs. non-DR3: 12 vs. 42%, Pc less than 0.05). However, there was no significant relationship between DR3 and IAAs after correcting for the number of DR4 alleles. No relationship was seen between age of onset, IAA level, and HLA typing in our population, and no relationship was found between ICA positivity and HLA antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Changes of vitamin D3 serum concentrations at the onset of immune-mediated type 1 (insulin-dependent) diabetes mellitus.

Several hormones such as 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3), alpha-MSH, or ACTH have been found to interact extensively with the immune system. In view of the immune-mediated nature of Type 1 (insulin-dependent) diabetes mellitus, 49 recently diagnosed diabetic patients were investigated in terms of serum 1,25-(OH)2D3-levels, 25-hydroxyvitamin D3(25-(OH)D3), alpha-MSH and ACTH, and compared with 42 healthy controls. A marked decrease of 1,25-(OH)2D3-levels was found at onset of Type 1 (insulin-dependent) diabetes compared to normal controls (39 +/- 2 vs 55 +/- 4 pg/ml, p less than 0.01). Grouping patients according to season (winter or summer) of diabetes onset and blood sampling, it was demonstrated that the decrease of 1,25-(OH)2D3 was primarily present during summer and due to a loss of the seasonal rhythm of this hormone observed in healthy controls (summer: patients vs controls 41 +/- 2 vs 63 +/- 4 pg/ml, p less than 0.001; winter: 37 +/- 3 vs 33 +/- 3 pg/ml, n.s.). Serum concentrations of 25-(OH)D3 were closely correlated with those of 1,25-(OH)2D3, both in controls (r = 0.55, p less than 0.002) and diabetic patients (r = 0.41, p less than 0.05), yielding a similar loss of seasonal variation also of this vitamin D3 metabolite in Type 1 (insulin-dependent) diabetic patients. No difference was found in the mean and median values of alpha-MSH and ACTH between IDDM patients and controls, although patients exhibited much higher variation of alpha-MSH levels than did controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

[Incidence and symptomatology of lung embolism in relation to the site of deep venous thrombosis].

The uncertainty about the true incidence of pulmonary embolism (PE) in connection with deep venous thrombosis (DVT) becomes evident when comparing the results of autopsy--vs. clinical studies, with the former showing a three-fold elevated rate of embolisation. In order to evaluate the percentage of clinically inapparent PE, all patients (65 females, 54 males, mean age 61.3 years) hospitalized between April 1989 and March 1990 with suspected DVT and/or PE underwent duplex-sonography and pulmonary scintigraphy. In 108 cases, DVT could be ascertained, whereas 11 patients only suffered from PE. In 57.4% of all DVT, PE was diagnosed. Of the 73 cases with PE, only 53.4% of the patient stated typical symptoms primarily. In more than 1/4 of the patients with primary symptoms of PE, no DVT could be diagnosed. There was no significant difference between the occurrence of PE in relation to the localisation of DVT, with 1/3 to 1/2 being asymptomatic. 1/4 of the patients with leg-thrombosis and 1/7 with thrombosis of the iliac vein did not complain of typical symptoms of thrombosis. Furthermore, an increased PE-rate seems to occur with an elevated ultrasound echogenity of the thrombus. As a result of the study pulmonary szintigrams seem to be indicated in all cases of DVT in order to evaluate the total PE risk.

Adult

[Results of local thrombolysis with special reference to diabetic metabolism].

The influence of diabetes on the primary and long-term success rate after 145 local thrombolyses in peripheral arterial disease stages III and IV was evaluated. 75 patients suffered from thrombotic, 62 patients from embolic occlusions, with eight patients suffering from thrombangitis obliterans. Regarding the localisation of vascular occlusion 0.6% suffered under an occlusion of the iliacal artery, 21% of the femoral artery, 16% of the popliteal artery, 7% of the vessel of the lower limb and 55.4% showed a combined occlusion of the femoral- and popliteal artery and the artery of the lower limb. In cases of embolic occlusions only marginal differences could be observed, while the primary success-rate of thrombotic occlusions showed greater differences between both groups (75% vs. 91%). During the follow-up, no differences between both groups could be established (patency-rate of 79% for both groups). The same applies to the prognostic factors: peripheral run off, length, duration of occlusion and the clinical stage (Fontaine IIb to IV). The remarkable differences between diabetic and non-diabetic patients in cases of occlusions of more than 16 cm (66% vs. 88% in primary and 55% vs. 77% in long-term success) can be explained by the high percentage of diabetic patients with poor run-off and microangiopathy. Regarding the above parameters, primary and long-term results seemed to be less in diabetic patients, even though a long-term patency could be observed in 2/3 of diabetic patients in stages IIb and IV with primary success.

Adult

Risk of progression to diabetes of low titer ICA-positive first-degree relatives of type I diabetics in southern Germany.

In a prospective study to evaluate the prevalence and predictive potential of circulating cytoplasmatic islet cell antibodies (ICA) and competitive insulin autoantibodies (CIAA), we screened 406 non-diabetic first-degree relatives of patients with Type I diabetes mellitus (n = 154 for CIAA). The prevalence of ICA was 2.5% (10/406) and of CIAA 0.6% (1/154) in ICA- and 10% (1/10) in ICA+ relatives at initial screening. The titer of ICA positivity in all relatives varied between 1:1 and 1:4. Values of elevated CIAA were 256 nU/ml of the CIAA+/ICA+, and 97 nU/ml of the CIAA+/ICA- relatives (normal range less than or equal to 39 nU/ml). Sera for repeat ICA and CIAA determination was obtained, and 70% of relatives were found to be again ICA+ after 1.5 years, 40% after 3 years, and 10% after 5.7 years. Both CIAA+ relatives were found to be again CIAA+ on follow-up. Intravenous glucose tolerance tests (IVGTT) were performed in all antibody-positive relatives. No decrease in first-phase insulin secretion (1 + 3 min) below the 1st percentile was observed in any of the ICA+ relatives during follow-up. No ICA+, but one CIAA+/ICA- relative had developed Type I diabetes after 5.6 years of follow-up. In summary, these results indicate that low titer ICA (less than 40 JDF units) are often transient and relatives with low titer ICA rarely progress to Type I diabetes. Elevated CIAA appear to be constant over time and associated with increased progression to overt diabetes.

Adolescent