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Biomedical subjects

G J Bruining

Publications and source records attributed to G J Bruining.

At least 73 records · Page 4Linked to original sources
PubMed1984

Clinical time-course and characteristics of islet cell cytoplasmatic antibodies in childhood diabetes.

Circulating islet cell antibodies (ICA) were present in high frequency (80%) early after diagnosis and decreased in the time course of childhood diabetes mellitus. The complement fixing ability of islet cell antibodies (CF-ICA) in the course of the disease appeared to depend on the titre of ICA: the coefficient of correlation between ICA and CF-ICA titres was 0.79 and all ICA's with a titre over 16 were complement-fixing. Incubating fresh frozen human pancreatic sections thrice rather than once with the children's sera, increased the detectability of complement fixation by a factor 1.4 in all ICA-positive sera. Thus tested, the detection of complement fixation per se did not appear to have a separate pathogenic significance, as the fraction of complement fixing ICA's was almost constant throughout the clinical course. The presence of ICA-IgG subclasses also was dependent on the ICA titre: above a titre of 16 mostly all four subclasses could be detected. Incubating the pancreatic tissue thrice rather than once with ICA-positive sera resulted in enhanced detectability of ICA-IgG1. Early in the course of childhood diabetes, including two prediabetic children, most of the IgG subclasses could be detected in ICA, but after a duration of one year IgG1 alone was mainly seen. In two other children, having a family history of insulin-dependency, restriction to the IgG2 subclass was found.

Adolescent↗
PubMed1984

Incidence of childhood diabetes in The Netherlands: a decrease from north to south over north-western Europe?

The incidence of childhood diabetes (0-19 years of age) in The Netherlands, where there is no nationalized health-care system, was investigated retrospectively in the years 1978 to 1980 inclusive. The method chosen was a questionnaire among all Dutch paediatricians and internal physicians acting as consultants. Ascertainment was by the same questionnaire held separately among the large Dutch membership of the Dutch Diabetes Association, employing the capture-recapture census method for calculation. For paediatricians the ascertainment was 94%, for specialists in internal medicine 75%. Before correction for ascertainment 1271 children were registered in the two surveys. The ascertainment-corrected annual incidence was 10.95/100000 for 0-19-year-old children, lower than in any other ascertained survey in north-western Europe published so far. The male:female ratio was the same as in other studies and no local geographical differences were found. Seasonal variation was absent in children 0-10 years old in the month the first insulin injection was administered. The data support the influence of unknown exogenous factors associated with the clinical onset of childhood diabetes.

Adolescent↗
PubMed1984

HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study.

This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens. A significant heterogeneity for the frequency of HLA-DR4 related to age of onset was observed. A significant deviation of the Hardy-Weinberg equilibrium was observed for the HLA-DR locus with an excess in patients of heterozygotes HLA-DR3, -DR4.HLA-B8, and HLA-B15 were not only secondary associated, but constituted with HLA-DR3 and -DR4, respectively, a haplotype in association with IDD. Nonrandom segregation of HLA-haplotypes was observed in multiplex families exemplified by an excess of HLA-identical affected sibpairs . Cross- overs between HLA-DR and GLO identified the HLA-DR segment as mainly involved in the association with IDD. Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. The segregation of GM allotypes to affected sibpairs was not significantly different from random segregation. The main conclusions from this study are that significant heterogeneity for age of onset exists and that the data are not compatible with simple genetic models including dominant, recessive, and intermediate models of inheritance. The data do require more complex models, involving two different HLA-linked (sets of) susceptibility genes.

Adolescent↗
PubMed1984

Relation of insulin-dependent diabetes mellitus (IDD) and the HLA-linked SB system.

This report deals with the question of the susceptibility for IDD association with the recently described HLA-linked SB system. The SB system is located centromeric of HLA-DR between HLA-DR and GLO. At present five specificities of the SB system, which behave as alleles, can be recognized. A total of 40 IDD patients and 96 normal controls were characterized for HLA-A, -B, -C, -DR and SB antigens. Our results confirmed the strong positive association of IDD with HLA-DR3 and -DR4 and the negative association of IDD with HLA-DR2. The genetic analysis of the SB system and IDD, however, demonstrated no significant association between alleles of SB and susceptibility for IDD. The analysis of association between alleles of HLA-DR and SB revealed no significant linkage disequilibrium in IDD patients and a significant linkage disequilibrium between SB1 and HLA-DR3 in the controls. These results suggest that the genes associated with susceptibility for IDD are primarily coded for telomeric of SB and tightly linked with HLA-DR.

B-Lymphocytes↗
PubMed1983

Autoantibodies to the insulin receptor in juvenile onset insulin-dependent diabetes.

Insulin-dependent diabetes mellitus (IDDM) usually begins in childhood or early adulthood, and its aetiology is thought to involve autoimmune damage to the islet cells that secrete insulin. To investigate an additional target of autoimmunity in IDDM we examined sera for antibodies to insulin receptors. Such antibodies were defined by their ability to compete with insulin for binding to insulin receptors and by their capacity to behave like insulin in activating lipogenesis in adipocytes. We now report the occurrence of anti-insulin receptor antibodies of the IgM class in the sera of 10 of 22 IDDM patients obtained before their treatment with exogenous insulin. Furthermore, two of five IDDM patients who were initially negative developed anti-insulin receptor antibodies during treatment with human or pork insulin. These findings suggest that autoimmunity to the insulin receptor may contribute to the pathophysiology of IDDM.

Autoantibodies↗
PubMed1983

Analysis of islet cell antibodies on frozen sections of human pancreas.

The sensitivity and specificity of the assay for islet cell cytoplasmic antibodies in human serum were examined using cryostat sections from fresh frozen pancreas. The specificity of the assay was close to 100% while the sensitivity was 40%-98% depending on the pancreas used. Inter-observer variation was 12-27%. End-point titres of islet cell antibodies varied with the sensitivity of each pancreas. End-point titration of the antibodies in two different laboratories using the same pancreas was significantly correlated (Spearman test p less than 0.001). We conclude that a reliable determination of islet cell antibody titres in human serum requires careful characterization of the sensitivity and specificity of each pancreas used as a source of frozen sections, in the indirect immunofluorescence assay.

Adolescent↗
PubMed1983

[Problems with indications for continuous subcutaneous insulin infusion in 2 juvenile patients with diabetes mellitus].

Continuous subcutaneous insulin infusion (CSII) using peripheral insulin pumps is only indicated if optimal conventional insulin treatment fails. If psychosocial variables are associated with chronic metabolic disregulation of the treated diabetes mellitus, it may be difficult to decide what came first: the chronic disregulation or the psychosocial variables. In childhood, disregulation of the diabetes may be related to stress-factors, generating a vicious circle. In two such minors CSII was tried with dissatisfying and potentially dangerous results.

Adolescent↗
PubMed1981

Prolonged galactorrhoea in a 6-year-old girl with isosexual precocious puberty due to a feminizing adrenal tumour.

A large cystic adrenal carcinoma was removed in toto from a 6 1/2-year-old girl with isosexual precocious puberty treated with cyproterone-acetate. Immediately following surgery, sever galactorrhoea developed, but was successfully treated with bromocriptine. The tumour fluid and pre-operative plasma samples contained highly elevated levels of both oestrogens and androgens. In addition prolactin values were high. One year after adrenalectomy all plasma hormonal values were normal for age, but galactorrhoea could still be elicited. The prolonged galactorrhoea is most likely the result of excessive oestrogen 'priming', whereas the hyperprolactinaemic effect of cyproterone acetate therapy remains uncertain.

Adrenal Gland Neoplasms↗
PubMed1976

Urinary creatinine excretion and lean body mass.

In a group of 34 adult and child subjects a high correlation (r = 0.988) was found between lean body mass, as determined by potassium-40 counting, and urinary creatinine excretion. The effect of technical errors was reduced by averaging the results of two or three 40K assays on each subject, and by making consecutive 3-day collections of urine. It appears that one can make a reasonable estimate of lean body mass from urinary creatinine excretion.

Adolescent↗
PubMed1976

Testosterone-estradiol-binding globulin in patients with Turner's syndrome: effects of estrogens and acute growth hormone administration.

The TeBG activity of plasma from patients with Turner's syndrome was measured quantitatively using polyacrylamide gel electrophoresis. Human growth hormone administration did not significantly change the plasma TeBG levels. However, oral replacement therapy with estrogens elevated plasma TeBG within 3 days; after 9 days these levels reached a maximum of three- to four-fold greater than that observed at a time prior to therapy.

Adolescent↗
PubMedDate not supplied

Continuous subcutaneous insulin infusion in children.

Insulin-dependent diabetes mellitus usually presents in childhood. Since it i is generally accepted that persisting metabolic derangements contribute to the development of micro- and macrovascular complications, a primary aim of the management of children with diabetes is to achieve near normalization of metabolism. In adults continuous subcutaneous insulin infusion (CSII) has been used to optimize control. Despite a reluctance amongst paediatricians to use CSII in children, several studies with pumps have been performed in adolescents. The results of these studies are contradictory with respect to acceptability and achieved metabolic control. Thus, some authors report a near normalization of blood glucose concentrations, whereas others only find a temporary improvement. Patient selection seems to account for many of these differences. This suggests that methods ought to be developed to predict success or failure of CSII in a particular adolescent patient. For diabetic toddlers with their age-specific problems CSII may be a therapy of choice. So far, good acceptability and improved metabolic control are reported in this group. More studies are needed to confirm this. It is important that the diabetic clinic as well as the patient is organized to high standard before starting CSII. Home blood glucose measurements, education, and a 24-h telephone service are essential factors for the management of diabetic children, treated conventionally or with CSII.

Adolescent↗
PubMedDate not supplied

Quantitative sensory examination in diabetic children: assessment of thermal discrimination.

Vibration perception thresholds (VPTs) and thermal discrimination thresholds (TDTs) were investigated in 55 insulin-dependent diabetic children aged 11.3 +/- 3.9 years (mean +/- SD) and in 81 controls. There was no significant difference in VPTs between the two groups. TDTs were significantly higher in the group of diabetic children (p less than 0.03). Eight diabetic children had abnormal thermal sensation and one child had abnormal vibratory sensation. TDT correlated positively with duration of diabetes mellitus (r = 0.25; p less than 0.05). Both investigations can be carried out easily and are unobtrusive, which is an important advantage in the examination of children.

Adolescent↗
PubMedDate not supplied

Insulin antibodies in diabetic children before treatment: a marker for islet B-cell destruction?

Insulin antibodies were measured in the sera of 28 newly diagnosed diabetic children (age 8.0 +/- 4.0 (+/- SD) years) prior to insulin therapy and after 3, 6, 9, and 12 months. The levels at diagnosis and after 12 months were compared to endogenous insulin production at onset and after 12 to 14 months. Endogenous insulin production was evaluated through the measurement of 24-h urinary C-peptide excretion, fasting plasma C-peptide levels and plasma C-peptide levels after glucagon stimulation. Insulin antibodies were detected in 29% of the patients (8 out of 28). In all but one patient antibodies binding porcine and human insulin were detected. No relationship was found between the presence of antibodies binding human or porcine insulin at diagnosis and age. After 1 year 27 out of 28 patients presented insulin antibodies. No relationship was found between the presence of insulin antibodies before therapy and 1 year after therapy. Insulin antibodies prior to diagnosis showed no relationship with the urinary C-peptide excretion at diagnosis (with antibodies 67 +/- 27%, without antibodies 76 +/- 11%). However, after 1 year significantly lower urinary C-peptide excretions were found in patients with insulin antibodies prior to therapy (with antibodies, 17 +/- 7%, without antibodies, 31 +/- 5%, p less than 0.02). Peak plasma C-peptide levels after 1 year were possibly lower in patients with insulin antibodies before treatment (with antibodies 0.17 +/- 0.06 nmol/l, without antibodies 0.26 +/- 0.04 nmol/l, p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗
PubMedDate not supplied

Increase in IDDM incidence in Bulgarian children (1974-1995).

The incidence of insulin-dependent diabetes mellitus (IDDM) in children on the Balkan peninsula varies between 2.45 and 10.00/100,000. The present study aimed to assess the trends in the IDDM incidence in children 0-14 years for a 22-year period in Eastern Bulgaria. The data were collected on the basis of the Varna Paediatric Diabetes Registry, both retrospectively and prospectively, with ascertainment of the primary source up to 98.8%. The mean annual IDDM incidence was 6.32/100,000 (95% CI 5.91-6.78), with the incidence in towns significantly higher than in villages: 7.24 vs 4.58/100,000, p < 0.0001. A linear trend of increase in the incidence with time was found, applying Poisson regression analysis. According to the model the age-adjusted incidence rose by 1.9% annually. The analysis revealed a significant linear trend of increase for children living in towns and for those aged 10-14 years.

Adolescent↗