Ultrasound shear wave velocity in skeletal muscle: A reproducibility study.

PURPOSE: The purpose of the study was threefold: to assess the reliability of shear wave velocities (SWV) measurements in normal skeletal muscles; to evaluate intra- and inter-operator reproducibility of measurements for a specific site of the muscle and for the mean value in the whole muscle. MATERIALS AND METHODS: Two sets of measurements were performed at three weeks intervals of each other on 16 volunteers by two radiologists on medial gastrocnemius and tibialis anterior muscles. Each muscle was evaluated in 5 different sites, with three measurements for each site in the transverse and longitudinal planes. Reliability of SWV measurements was assessed by means of intraclass correlation coefficient (ICC). RESULTS: Reliability of the three independent SWV measurements was excellent, slightly better in the longitudinal plane. Inter/intra-operator reproducibility per site was fair to good in the longitudinal plane and poor to fair in the transverse plane. For global values of the whole muscle, ICC showed good agreement in the longitudinal plane and fair agreement in the transverse plane. CONCLUSION: Quantitative SWV measurements are reliable when performed in rigorous conditions. In conditions that mirror clinical practice, inter/intra-operator reproducibility is moderate, better for longitudinal compared to transverse plane.

High dose nicotinamide fails to prevent diabetes in BB rats.

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.

The soluble receptor of interleukin 2 is not a serum marker of the autoimmune activity in type I diabetes mellitus.

In order to determine if soluble interleukin 2 receptor (IL2R) was useful as a marker in screening for early Type 1 diabetes and in monitoring immunological treatment, we assayed serum IL2R levels in 67 controls, 43 patients with newly diagnosed diabetes and 28 first degree relatives of diabetic patients (5 subjects were islet cell antibody positive). In 23 diabetes, specimens were analysed at 3 and 6 months after diagnosis whether or not cyclosporin A was administered. Seven patients were in a clinical trial using anti IL2R monoclonal antibody and cyclosporin A. Since IL2R level in the normal population is elevated in the first 5 years of life then decreases until adulthood (age:IL2R correlation between 0 and 15 years: r = -0.42, P less than 0.05), subjects were carefully matched in age. In recent onset diabetes, this negative correlation disappeared and IL2R levels tended to decrease particularly in younger subjects. In Type 1 prediabetic subjects presenting persistent islet-cell antibody serum IL2R was not elevated. During immunological treatment of recent onset diabetes, serum IL2R remained stable and was not modified by cyclosporin A. As expected IL2R became undetectable during treatment with anti IL2R MC Ab. But it rebounded when treatment was stopped with no effect on remission. We concluded that IL2R levels in Type 1 diabetic patients is not useful in screening autoimmune activity or in evaluating the effectiveness of immunosuppressors.

Different TH2-TH1 balance in V beta 8 and V beta 6 subsets of splenocytes in NOD females in the early phase of diabetogenesis.

Non-obese diabetic (NOD) mice spontaneously develop T-cell-mediated autoimmune diabetes. Initial work on the diabetogenic T-cell repertoire indicated that autoreactive T lymphocytes were polyclonal but that the presence of specific subsets (V beta 8 or V beta 6) might be required for induction of the disease. Further functional analysis of NOD mice T lymphocytes was limited because of the relative anergic state of these cells due to abnormal patterns of cytokine secretion. The purpose of the present study was to establish experimental conditions allowing the exploration of the functional features of minor T-lymphocyte subsets in vitro using low doses of cofactors. The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. No significant bias in T-cell receptor usage was noted in the spleen of these animals, whereas V beta 6 + lymphocytes could be very efficiently stimulated by interleukin-4 and also produce low but detectable amounts of interleukin-4 during the pre-diabetic period in female NOD mice. These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process.

Contribution of the comonomers to the bulk and surface properties of methacrylate copolymers.

Relationships between formulation, bulk properties, and surface properties are investigated on series of copolymers prepared with hydroxyethylmethacrylate (HEMA), methylmethacrylate (MMA), and ethylmethacrylate (EMA) monomers, and on the homopolymers PMMA and PHEMA. The bulk water content, swelling ratio, and static (sessile drop and captive bubble) and dynamic (Wilhelmy plate technique) contact angles and the electrokinetic potential (streaming potential) are measured. The bulk water content and swelling ratio of HEMA copolymers are proportional to the amount of HEMA and are linearly correlated to the contact angle hysteresis. Periodic instabilities in the wetting cycles, similar to Haines jumps, are observed with HEMA copolymers and support a bidirectional relaxation of the hydrophilic groups respectively towards external water and capillary water. The origin of the electrokinetic potential of these nonionizable polymers is attributed to specific adsorption of [Formula: see text] ions. Its dependence on surface hydrophobicity and statistical length of the side-chains is interpreted in terms of the properties of water molecules near the interface.

Paradoxical lessening of autoimmune processes in non-obese diabetic mice after infection with the diabetogenic variant of encephalomyocarditis virus.

In order to gain insight into the interaction between autoimmunity and viral infection in the onset of insulin-dependent diabetes, non-obese diabetic (NOD) mice which spontaneously develop autoimmune diabetes were inoculated with the diabetogenic variant of the encephalomyocarditis virus (EMCV-D) before the onset of the disease. The pre-diabetic period was divided into two phases: the early phase (days 88 to 116) during which development of spontaneous diabetes is rare and the late phase (day 123 to 200) during which the incidence of spontaneous diabetes is high. As controls ICR mice of common ancestry were also inoculated. During the early phase diabetes was observed in 4/10 inoculated, 0/13 control NOD and 7/13 inoculated ICR males vs. 6/12 inoculated, 1/11 control NOD and 0/15 inoculated ICR females. However, in NOD female, virus-induced diabetes prevalence was variable from one experiment to another. In parallel the flow cytometric analysis showed a high percentage of L3T4+ T lymphocytes in the pancreas of inoculated female NOD mice 10 days after the infection. At this time a large proportion of both L3T4+ and Ly-2+ cells expressed the interleukin 2 receptor. During the late phase no new case of diabetes occurred in inoculated NOD mice but one case was observed in control NOD males and five in control NOD females. This prevention of autoimmune diabetes was constantly found in other experiments. Insulitis was milder in inoculated NOD mice of both sexes than in control NOD. Adoptive transfer of diabetes into irradiated 8-week-old males by splenocytes from 28-week-old females was successful in five out seven attempts with control splenocytes and in zero out of six attempts with splenocytes from inoculated mice. This immunosuppression was specific as the ability of lymphocytes to respond to soluble or allogeneic antigens was preserved. In the early phase EMCV-D precipitated the onset of diabetes in females NOD mice by amplifying L3T4+ T lymphocyte-mediated immune mechanisms. During the late phase viral infection had lessened immune processes in animals which had resisted or recovered from virus-induced diabetes.

Dietary protection against diabetes in NOD mice: lack of a major change in the immune system.

Pregestimil, a hypoallergenic infant formula in which casein hydrolysate replaces protein, protects NOD mice against diabetes, a T-cell-mediated autoimmune disease. Female and cyclosphosphamide (Cy)-treated male NOD mice were used to assess whether a modification of cellular immune mechanisms occurred when animals were fed Pregestimil from weaning to 110 days of life. Insulitis, sialitis and thyroiditis were observed, and the splenic T-cell proliferative response was measured. The ability of splenic T-cells of NOD mice in the Pregestimil group to transfer diabetes adoptively to young irradiated male NOD mice was also assessed. Pregestimil protected female NOD mice against spontaneous diabetes and male NOD mice against acute Cy-induced diabetes. Addition of bovine serum albumin (10%) to the diet did not alter the preventive effect. The Pregestimil diet also lessened insulitis severity in Cy-treated males, though not in females. Sialitis and thyroiditis, observed mainly in females, were not modified by the diets. The TCR-mediated proliferative response of splenocytes tended to increase specifically in Pregestimil-fed and Cy-treated males. Sensitivity to IL-2 was improved. In females, the TCR-mediated proliferative response and the ability of T cells to transfer diabetes adoptively were unchanged. It is concluded that the protective effect of Pregestimil against diabetes in NOD mice cannot be explained by major changes in peripheral immune response.

Humoral immunity against glutamic acid decarboxylase and tyrosine phosphatase IA-2 in Lambert-Eaton myasthenic syndrome.

Some beta-cell-specific autoantigens also are present in the central nervous system. Furthermore, stiff man syndrome, an autoimmune neurological disease, is frequently associated with diabetes and shares with this one an anti-GAD and IA-2 humoral immunoreactivity. We wondered whether these autoantibodies could be found in other neurological diseases with a present or supposed autoimmune origin. So, anti-GAD65 (GAD65A) and anti-IA-2 (IA-2A) autoantibodies were assayed in various neurological diseases. There was a higher prevalence of such antibodies in Lambert-Eaton myasthenic syndrome (LEMS) (GAD65A, 35%; IA-2A, 21%; double positivity, 18%) compared to amyotrophic lateral sclerosis (18%, 12%, and 12%, respectively) and multiple sclerosis (10%, 3%, and 3%, respectively). In LEMS, the humoral reaction was more frequent and/or appeared earlier in the paraneoplastic forms. The detection of such autoantibodies in patients with small-cell lung carcinoma (SCLC) without LEMS suggests that these autoantigens, GAD65 and IA-2, could be produced by SCLC tissue.

Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications.

Glutamic acid decarboxylase autoantibodies (GAD-A) and tyrosine phosphatase IA-2 autoantibodies (IA2-A) were measured in sera of 50 recently diagnosed (<6 wk, 33% younger than 15 yr), 19 short-term (1 to 9 yr, 35% with onset age below 15 yr) and 89 long-standing diabetic patients (>10 yr, 57% with onset age below 15 yr). Complications were assessed by clinical examination, retinal angiographs and microalbuminuria measurement. Both prevalences and levels of GAD-A and IA2-A decreased with increasing duration of diabetes. However even in those with long duration diabetes, 15 to 63% of the sera were still positive for one or two antibodies. In the group with onset after the age of 15 yr, significantly higher prevalences and levels of GAD-A (but not IA2-A) was observed in comparison with the group with earlier onset. No association was found with any microvascular complications in any group. We conclude that GAD-A and IA2-A persist in some diabetic patients, despite a long duration. Persistence of GAD-A was greatest in those with postpubertal disease onset. We speculate that persistence of some beta-cells or specific environmental factors can sustain one autoimmune reaction especially in some postpubertal-onset diabetic patients.

Autoimmune polyendocrine failure--type 1 (insulin-dependent) diabetes mellitus and hypothyroidism--after allogeneic bone marrow transplantation in a patient with lymphoblastic leukaemia.

In this report we describe a patient who, after allogeneic bone marrow transplantation from her HLA-identical sister, developed polyendocrine failure in the form of Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism. This was the result of the transfer of donor lymphoid cells which were activated by allogeneic bone marrow transplantation. The full chimerism of the recipient was demonstrated by restriction fragment length polymorphism analysis from nucleated blood cells and fibroblast DNA. During the 9-year follow-up, the donor developed hypothyroidism and signs of pre-Type 1 diabetes. This clinical observation resembles the adoptive transfer of diabetes observed in non-obese-diabetic mice and BB rats and confirms the role of immune processes in the pathogenesis of this disease.