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D Cheţa

Publications and source records attributed to D Cheţa.

At least 19 recordsLinked to original sources

Immunological aspects of diabetes.

Notable progress was achieved by the investigations on the immunology of diabetes. Studies of immunogenetics have demonstrated that Type 1 (insulin-dependent) diabetes shows a primary association with the HLA class II genes (e.g., with HLA-DR3 and DR4 in Caucasoid populations), a determining features of this type of the disease. Besides, it presents a wide variety of autoantibodies, such as islet-cell cytoplasmic antibodies (ICA), islet-cell surface antibodies (ICSA), complement-fixing islet-cell antibodies (CF-ICA), antibodies to a Mr-64000 islet-cell protein, and many studies are trying to evaluate their pathogenic and predictive role. Various changes of cell-mediated immunity have been also described. The proportion of activated T cells in circulation is increased in patients with Type 1 diabetes. It was assumed that the T cells are the main cause of pancreatic beta-cell damage. Type 1 diabetes is actually considered as a chronic autoimmune disease, with several stages of evolution leading to the destruction of the pancreatic beta-cells, with a consecutive gradual decrease of insulin secretion. From the therapeutic point of view, many problems are raised by insulin immunogenicity, mainly depending on the so-called "contaminants". To avoid phenomena of allergic reactions, immunological insulin-resistance, lipodistrophy, a.o., highly purified and human type insulins have been prepared. The insulin autoantibodies (IAA) detected before the clinical onset of Type 1 diabetes are considered a new marker of autoimmunity. New hopeful prospects are opened by diabetes immunotherapy, in which Cyclosporin A detains a particular role, although it should be used only in special conditions, under strict clinical observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation

Evaluation of an intensified insulin treatment and teaching programme as routine management of type 1 (insulin-dependent) diabetes. The Bucharest-Düsseldorf Study.

It has been questioned whether aiming at near-normoglycaemia by intensified insulin treatment regimens is feasible and safe for the majority of patients with insulin-dependent diabetes. In this study, intensified insulin injection therapy (including blood glucose self-monitoring and multiple insulin injections) based upon a 5-day inpatient group teaching programme was evaluated in Type 1 (insulin-dependent) diabetes mellitus in the centralised health care system of Bucharest. One hundred patients (group A, initial HbA1 12.5%) were followed for 1 year on their standard therapy (individual teaching, no metabolic self-monitoring), and thereafter for 1 year on intensified therapy. Another 100 patients (group B, HbA1 12.3%) were followed for 2 years on intensified therapy. A third 100 patients (group C, HbA1 11.7%) were assigned to a basic 4-day inpatient group teaching programme with conventional insulin therapy (including self-monitoring of glucosuria and acetonuria) and followed for 1 year. Mean HbA1 remained unchanged after standard treatment (group A: 12.8% at 12 months), but decreased during intensified therapy (group A: 10.1% at 24 months; group B: 9.3% at 12 months, 9.5% at 24 months; p less than 0.0001). In group C, no change was found compared to standard treatment (i.e. group A at 12 months). Incidence rates of ketoacidosis were 0.16 episodes per patient per year during standard treatment, 0.01 during intensified treatment (p less than 0.01) and 0.04 in group C (p less than 0.025). Hospitalisation rates were reduced by 60% during intensified therapy and by 40% in group C. Frequency of severe hypoglycaemia was not significantly different between the three treatment regimens. Thus, under the condition that insulin treatment is based upon a structured and comprehensive training of the patient, intensified insulin injection therapy performed as routine treatment of Type 1 diabetes significantly lowers HbA1 levels without increasing the risk of severe hypoglycaemia.

Adolescent

Cytoenzymochemical effects of some antiblastic drugs and prediction of response to chemotherapy in acute leukemias.

Over 20 cytoenzymochemical tests were carried out in 152 patients with different types of acute leukemia to estimate the effects of some antiblastic drugs such as L-asparaginase, Purinethol, Methotrexate, Endoxan, Vinchristine, Cytosine Arabinoside a.o. The patients selected for the study were carefully examined before treatment at different moments during and/or at the end of the treatment. The effects of these drugs on the blast cells were mild when the cellular populations had a low rate of nucleic acid synthesis, high glycogenic score and high amounts of lipids or an important oxidative enzymatic activity. The enzymatic prediction tests: the acid phosphate deviation test and the succinic dehydrogenase inhibition test including the variant suggested by some of the authors - the latic dehydrogenase inhibition test - gave satisfactory results only in certain cases of acute leukemia.

Acid Phosphatase

The perception threshold to an electric stimulus deeply applied in the lower limbs in normal and diabetic subjects.

The loss of sensitivity to nociceptive stimuli is one of the main factors involved in the pathogeny of diabetic gangrene. The aim of this study was to develop a simple and practical method for selecting the cases prone to such a complication. The perception threshold (either voltage, mV or current, microA) was determined in 137 randomly selected diabetic patients and 38 non-diabetic controls, by an original electronic device using sinusoidal waves, delivered through two electrode needles introduced at a depth of 0.5 cm at two points located on the anterior aspect of the shank about 12 cm apart. At each of the eight frequencies studied (10, 20, 50, 100, 200, 500, 1000 and 2000 Hz) three electrical parameters (voltage across the needle electrodes, the resistive and the capacitive current component) were recorded when the subject first perceived the stimulus. A significantly higher perception threshold was found in diabetic patients vs. non-diabetic subjects, at all frequencies studied and with all three electrical parameters recorded. A greater difference in the perception threshold between diabetic and non-diabetic subjects (a ratio higher than 3) was, however, found using the resistive component of the current and at frequencies higher than 200 Hz.

Adolescent

Behaviour of leukocyte acid phosphatase in various chronic diseases.

Leukocyte acid phosphatases were investigated in 146 patients with different chronic diseases. The method of investigation used was that of Kaplow and Burstone slightly modified by the authors in what regards the pH of the incubation medium. Normal or slightly increased scores were observed in the granulocytic series of patients with chronic myeloid leukemia. In patients with rheumatoid arthritis, chronic hepatitis, lupus erythematosus disseminatus and chronic lymphocytic leukemia a moderate enzymatic activity was generally observed in the lymphocyte and more marked in severe forms of disease. A marked increase of the enzyme activity was observed in patients with myeloma. The possibility of a correlation between the intensity of enzyme activity and immunoglobulin formation is discussed.

Acid Phosphatase

The variations of the serum IgD and of the circulant immune complexes in diabetic patients.

The levels of serum IgD and of the circulating immune complexes (CIC) were determined in 168 diabetic patients, of whom 78 with type 1, 59 with type 2 and 31 with the so-called "intermediary" type of the disease, in comparison with 124 non-diabetic subjects for IgD and 100 for CIC. The results revealed very low IgD titres (less than 1 mg%, considered undetectable) in almost 3/4 of the cases; values over 1 mg% were recorded mostly in the cases of type 1, followed by those of "intermediary" and of type 2 diabetes. The mean CIC values of 67.13 +/- 36.53 optic density units (O.D.U.) were significantly higher than in the non-diabetic controls. Certain differences with respect to age, diabetes type, duration of the disease and of the insulin therapy were also recorded. The data are interpreted with caution, further investigations being necessary to the assertion of definite conclusions.

Adult

Not only quantitative but also qualitative changes of serum immunoglobulins in diabetes mellitus.

To extend previous observations on the quantitative changes of IgA and other serum Ig in diabetics, additional immunochemical investigations were carried out in 96 patients, 63 males and 33 females, mean age 43.5 +/- 15.7 years, 51 with type 1 (insulin-dependent) and 45 with type 2 (non-insulin-dependent) diabetes. The immunological data were correlated with the clinical-metabolic aspects. In the whole group, the IgA level was increased (144.1 +/- 57.2 I.U.). Significant differences were recorded with respect to age for IgG, to age and diabetes type for IgA, to sex for IgM. Qualitative Ig changes, reflecting disturbances of molecular structure, mainly for IgG, seldom for IgM, but never for IgA, were observed in 20% of the patients with both types of diabetes, more seldom in cases with long disease duration. The IgG with qualitative changes were purified and their functional capacity of inhibiting the natural cytotoxic activity (NK) was tested in comparison with that induced by pretreatment of the effectory cells with normal IgG. Some of these modified IgG showed a reduced capacity of inhibiting the NK activity. These data confirm the existence of certain quantitative changes of the main serum Ig in diabetics and reveal the presence of qualitative disorders of the IgG molecules, with consequences on their functionality.

Adult

No relationship between insulin antibodies and hypoglycemia in insulin-treated diabetic patients.

It has been speculated that insulin antibodies may contribute to the hypoglycemic attacks in insulin-treated diabetic patients. To address this hypothesis, we analyzed in a first part of the study the frequency to hypoglycemia in two groups of diabetic patients, one (Group A, 38 cases) with at least two episodes of severe hypoglycemia in the last year and another (Group B, 38 cases) without severe hypoglycemia in the last 3 years. In the second part of this study, we analyzed the frequency of severe and moderate episodes of hypoglycemia in another two groups of diabetics, one (Group C, 32 cases) with high insulin antibody titre (greater than or equal to 20% binding, mean +/- SD 31.2 +/- 8.1%) and another with low insulin antibody titre (less than 10% binding, mean +/- SD, 5.1 +/- 2.2%). No significant difference was found for bound insulin between diabetics with frequent hypoglycemic episodes (2.3 +/- 0.2/patient/year--Group A) and those without severe hypoglycemic episodes (Group B), i.e., bound insulin 4.89 +/- 3.21% in group A versus 5.32 +/- 4.5% in group B. Conversely, the frequency of severe episodes of hypoglycemia was similar in diabetic patients with high (31.2 +/- 8% binding in group C) and respectively low (5.1 +/- 2.1% binding in group D) insulin antibody titre, i.e., 0.15 episodes/patient/year in group C and 0.17 episodes/patient/year in group D.

Adult

A study on the types of diabetes mellitus in first degree relatives of diabetic patients.

The genetic characteristics of the diabetic types have been assessed by following up their frequency in first degree relatives of some non-selected diabetic patients, registered at eight different centers of the country. Out of 1,003 non-diabetic controls only 46 (4.6%) had 52 diabetic relatives, 65.4% of type 2 (non-insulin-dependent). Comparatively, out of the 704 patients, 172 (24.4%) had 229 diabetic first degree relatives, 72.5 of type 2. Out of 231 type 1 (insulin-dependent) diabetic patients, 29 (12.6%) had 34 diabetic relatives, 55.9% of type 1. Out of 300 type 2 patients, 99 (33.0%) had 121 diabetic relatives, 84.0% of type 2. The other 173 diabetic patients presented an "intermediary" type of the disease (needing insulin many years after onset). Forty-four (25.4%) of them had 64 diabetic relatives, 67.2% of type 2, 20.3% of type 1 and 12.5% with "intermediary" diabetes. The five times higher frequency of diabetes in patients' relatives versus controls is pointed out. Type 2 diabetic relatives predominated. The proportion of probands with diabetic relatives increased from 4.6% in non-diabetics to 12.6% in type 1, to 25.4% in "intermediary" diabetes and to 33.0% in type 2. The heredity of type 1 prevailed in type 1 and that of type 2 in type 2 and in "intermediary" diabetes. The fact that "intermediary" diabetes tends towards type 1 (insulin-dependent) as therapy and towards type 2 (non-insulin-dependent) as heredity might be an argument supporting the controversy on the diabetic syndrome classification.

Adult

Decrease of serum immunoglobulin M levels in some diabetic patients.

Contradictory results have been published on serum immunoglobulin levels in diabetes. Our study population consisted of 26 "juvenile" IDDM patients (males/females 14/12, mean age 15.8 +/- 2.4 yrs), 42 "adult-onset" IDDM patients (25/17, 45.1 +/- 15.2 yrs), 62 NIDDM patients (27/35, 59.8 +/- 7.7 yrs), 128 controls. IgM has been measured by a highly standardized endpoint radial immunodiffusion. Since age and sex significantly influence serum IgM levels, we calculated Z values using the formula: log (Xobs:Xexp): SDexp, where Xobs is the measured IgM in any individual and Xexp and SDexp are the expected (geometric) mean and standard deviation of the log IgM values for each year of age in both sexes, as previously calculated by orthogonal polynomials from a large population of "laboratory controls" (n = 755; 10-70 yrs). These Z values (+/- SD) in juvenile IDDM (-0.442 +/- 0.988) and NIDDM (-0.559 +/- 1.215) were significantly lower (P = 0.035 and P less than 10(-3)) than in "laboratory controls" (0 +/- 1). Values in adult IDDM (-0.0225 +/- 1.213; P = 0.24) and in controls (-0.018 +/- 1.04) did not differ significantly from the "laboratory controls". The prevalence of diabetes within the four quartiles of the IgM distribution differed significantly from the one expected according to the null hypothesis (chi-square = 42.2; 3df; P less than 10(-4]. This is also applied to juvenile IDDM (P less than 0.05) and NIDDM (P less than 10(-4], but not to adult-onset IDDM. These results suggest that the low IgM levels may partly contribute to the poorly explained increase in susceptibility to infections in some diabetics.

Adolescent