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Biomedical subjects

R Holl

Publications and source records attributed to R Holl.

18 recordsLinked to original sources
PubMed2006

Beta-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

BACKGROUND: In adults, a fraction of diabetic individuals with beta-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood (LADA). The occurrence of beta-cell autoantibodies in European children and adolescents with T2DM has not been reported so far. METHODS: The frequency of beta-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in 7050 diabetic children and adolescents. The type of diabetes was classified by paediatric diabetic specialists based on the clinical presentation. Children with non-insulin dependent T2DM over a one year period were studied separately. RESULTS: A total of 6922 children were clinically classified as having type 1 diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the children with T2DM had at least one detectable beta-cell autoantibody. These children did not differ significantly from the children with T2DM and without autoantibodies in respect of age, gender, weight status, lipids, blood pressure, C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti-thyroidal antibodies and insulin treatment during follow up. In the subgroup of the 38 children with T2DM without insulin requirement over a one year period, autoantibodies occurred in 32%. These 12 children were predominantly obese (67%), female (67%), and in the pubertal age range. CONCLUSION: beta-cell autoantibodies were detectable in a subgroup of initially non-insulin dependent diabetic children and adolescents with the clinical appearance of T2DM. Following the terminology "latent autoimmune diabetes in adulthood (LADA)", this subgroup might be classified as "LADY" (latent autoimmune diabetes in youth).

Adolescent↗
PubMed2005

Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function.

AIMS/HYPOTHESIS: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes. MATERIALS AND METHODS: To estimate C-peptide levels and autoantibody presentation, patients underwent a meal-stimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP. RESULTS: The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA(1)c after adjustment for insulin dose (p = 0.04). CONCLUSIONS/INTERPRETATION: These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recent-onset type 1 diabetes.

C-Peptide↗
PubMed2001

Serum leptin, gonadotropin, and testosterone concentrations in male patients with anorexia nervosa during weight gain.

Amenorrhea in female patients with anorexia nervosa is associated with low leptin secretion, thus suggesting a causal link. In an attempt to address the hypothesis that leptin also influences the hypothalamo-pituitary-gonadal function in males, we studied three male patients with acute anorexia nervosa longitudinally. Serum levels of leptin, LH, FSH, testosterone, and SHBG were measured on a biweekly basis during weight gain. Leptin levels at low body mass index values were below the 5th percentile. During weight gain, leptin levels reached or surpassed the 95th percentile. The temporal dynamics of body mass index and fat mass were closely related to those of leptin concentrations in serum. Leptin increments were paralleled by increments of gonadotropins, testosterone, and the free androgen index (FAI). In each of the patients, serum concentrations of leptin were positively correlated with those of testosterone (P = 0.0001, P = 0.01, P = 0.07, respectively) and FAI (P = 0.0001, P = 0.0001, P = 0.09, respectively). In addition, in the combined data set of all patients changes of leptin over time were positively correlated with changes in LH (P = 0.01), FSH (P = 0.0001), testosterone (P = 0.002), and FAI (P = 0.002). In conclusion, these data suggest that leptin might also play an important role in the regulation of the hypothalamo-pituitary-gonadal axis and fertility in underweight males as has previously been shown in underweight females.

Adipose Tissue↗
PubMed2001

Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes.

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

Adolescent↗
PubMed2000

Case of XXXXY syndrome. Development throughout adolescence and endocrine aspects.

49,XXXXY syndrome is a very rare condition that is associated with a considerable more severe phenotype than classic 47,XXY Klinefelter syndrome. We present a patient with 49,XXXXY syndrome, who was first presented to an endocrinological unit at the age of 12.5 years with prepubertal genitalia. He was then lost from follow-up and showed clear clinical and biochemical signs of hypergonadotropic hypogonadism when presenting again at the age of 16 years. The patient was started on testosterone replacement therapy. This case is reported to underline the need for thorough endocrinological follow-up examinations in males with X polysomies.

Adolescent↗
PubMed1997

Silastic catheters for home antibiotic therapy in patients with cystic fibrosis.

UNLABELLED: Repeated 14-day courses of intravenous antibiotic therapy for patients with cystic fibrosis (CF), who have been colonized with Pseudomonas aeruginosa (PA), is one currently accepted treatment. Conventional intravenous cannulas for antibiotic delivery often have a short line life leading to frequent venipunctures. Therefore we used silastic catheters as a peripheral venous access. Silastic catheters (15 cm, 0.6 mm diameter) were inserted 10 cm into a cubital vein in 15 patients with CF (age 5-32 years) for 20 antibiotic courses. After the antibiotic infusion the catheter was flushed with 200 U heparin (2 ml Vetren). In all patients the antibiotic therapy was delivered as a home therapy. In 15 antibiotic courses the silastic catheter could be continuously used for 14 days. One patient with methicillin resistant Staphylococcus aureus received antibiotic therapy for 54 consecutive days using the same silastic catheter. The catheter had to be removed in four courses: once because of thrombophlebitis with local inflammation, once because of burning pain during infusion and occlusion twice. In one case the patient removed his catheter because of technical problems. No other serious side effects occurred. Ten patients had previously received intravenous antibiotics at least once. The median line life of the last used conventional peripheral cannula of all patients was 4 days versus 14 days with the use of the silastic catheter (P < 0.005). All patients preferred the silastic catheter to other venous access. CONCLUSION: Because of the long line life and easy handling, silastic catheters may be an alternative venous access to perform home antibiotic therapy in patients with CF.

Adolescent↗
PubMed1997

Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects.

Ambulatory blood pressure (ABP) monitoring is increasingly used to evaluate the blood pressure of children and adolescents. The upper normal ABP values in the pediatric age group are still unknown, because reference values based on a sufficiently high number of healthy children have not yet been published. In this multicenter trial, we pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm. The study was carried out by seven centers according to a common protocol. The 50th percentile for 24-hour systolic ABP increased moderately with height, from 103 to 113 mm Hg in girls and from 105 to 120 mm Hg in boys. The 50th percentile for diastolic 24-hour means was 66 +/- 1 mm Hg, irrespective of height or gender. Diastolic daytime means were 73 +/- 1 mm Hg, which is remarkably high compared with reference values for casual blood pressure. The mean nocturnal systolic and diastolic ABP (midnight to 6 AM) was 13% +/- 6% and 23% +/- 9% lower compared with the daytime means (8 AM to 8 PM), respectively. This multicenter study provides well-based limits of normal ABP in mid-European children.

Adolescent↗
PubMed1994

Familial anaplastic ependymoma: evidence of loss of chromosome 22 in tumour cells.

A family with anaplastic ependymomas, histologically verified in three cases and neuroradiologically suggested in a fourth, is presented. Two healthy brothers both had two affected sons. All four male patients were younger than 5 years at the time of diagnosis. Two boys died before the age of 3 years. Genotype analysis (with polymorphic DNA markers for chromosome 22 and interphase cytogenetic analysis) of one of the tumours showed a subpopulation of tumour cells with monosomy of (part of) chromosome 22. Non-neoplastic cells of this patient showed a normal karyotype. These findings give further evidence for the role of a tumour suppressor gene on chromosome 22 in the pathogenesis of familial ependymal tumours.

Brain Neoplasms↗
PubMed1993

Prevalence of autoantibodies to the 65- and 67-kD isoforms of glutamate decarboxylase in insulin-dependent diabetes mellitus.

We investigated the presence of autoantibodies to baculovirus-expressed human recombinant 65- and 67-kD isoforms of glutamate decarboxylase (GAD65 and GAD67) in insulin-dependent diabetes mellitus (IDDM). In the immunoprecipitation test using [35S]methionine-labeled GADs antibodies to GAD65 were detected in 13/15 (87%) islet cell antibody (ICA)-positive and in 1/35 (2.9%) ICA-negative first-degree relatives of patients with IDDM, in 6/11 (54.5%) ICA-positive nondiabetic schoolchildren, and in 35/50 (70%) patients with newly diagnosed IDDM. GAD67 antibodies were positive only in five (33%) of the ICA-positive relatives (P < 0.05) and in nine (18%) IDDM patients at onset (P < 0.00001). After onset of IDDM antibodies to GAD65 and GAD67 declined but were still positive in 25 and 9.4% of subjects with long-standing IDDM (> 10 yr). In all study groups antibodies to GAD67 were only detected in GAD65 antibody-positive sera. An immunotrapping enzyme activity assay for GAD65 antibodies was positive in 64/75 (85.3%) of sera that were GAD antibody positive in the immunoprecipitation test (r = 0.870, P < 0.0001). In two (2.7%) sera GAD65 antibodies that block GAD enzyme activity were found. Our data suggest that antibodies to GAD65 but not to GAD67 represent sensitive markers for preclinical and overt IDDM. The immunotrapping assay here described represents a valuable technique for specific and sensitive screening for GAD antibodies.

Antibody Specificity↗
PubMed1988

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin.

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 micrograms hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.

Adenoma↗
PubMed1987

[Urinary steroid profile in Cushing syndrome and in tumors of the adrenal cortex].

The analysis of 24-h excretion profiles of urinary steroids in 18 patients suffering from Cushing's syndrome or adrenocortical tumors revealed typical patterns when compared to 37 healthy control persons, 24 patients with obesity, and 6 patients with hirsutism. The validation of eight criteria--increased excretion of free cortisol, 6 beta-hydroxycortisol, 20 alpha-dihydrocortisol, 11 beta-hydroxyandrosterone, and 3 beta-hydroxy-5-en steroids, decreased ratio of tetrahydrocortisone (THE) to tetrahydrocortisol (THF), and increased ratios of THF to allotetrahydrocortisol (a-THF) and metabolites of androgens (AM) to metabolites of cortisol (CM)--afforded reliable detection of disorders in steroid biosynthesis. The analysis of urinary steroid profiles can therefore be recommended as a screening procedure in patients with clinical symptoms of disorders in steroid production and/or metabolism.

17-Hydroxycorticosteroids↗
PubMed1985

[Global pituitary stimulation test with releasing hormones].

The endocrine function of the thyroid and gonads has for long been investigated using the corresponding releasing hormones (TRH- and LHRH-test, respectively). The adrenal cortex has, up to now, been stimulated using insulin-induced hypoglycaemia or lysine-vasopressin and growth hormone stimulated using arginine. New diagnostic possibilities have arisen with the isolation of the corresponding releasing-hormones, CRF and GRF, and with the availability of these too for clinical use. Using the four above mentioned releasing-hormones in a global pituitary-stimulation-test, the secretion of ACTH, cortisol, STH, TSH, LH, FSH and prolactin hormones can now be examined together.

Adrenocorticotropic Hormone↗
PubMed1984

Evidence for ACTH-unrelated mechanisms in the regulation of cortisol secretion in man.

In an attempt to elucidate the significance of ACTH independent mechanisms in the regulation of cortisol secretion in man, the dynamics of plasma ACTH and cortisol levels were studied in response to different stimuli. The cortisol response to small amounts of exogenous ACTH and to insulin induced hypoglycemia was preceded by an increase in ACTH levels appropriate to explain the increase in cortisol. In contrast, after administration of methamphetamine, there was an increase in cortisol levels in the absence of any changes in ACTH concentrations. Apparently, the methamphetamine induced cortisol secretion was not mediated by radioimmunoassayable ACTH. A diurnal rhythm was observed for the responses to hypoglycemia and to methamphetamine with larger cortisol responses in the evening as compared to the forenoon. These changes were not accompanied by parallel changes in the ACTH responses. From these differences, additional evidence is provided for the importance of ACTH independent mechanisms in the regulation of cortisol secretion.

Adrenal Cortex↗
PubMed1984

Evidence for extrapituitary mechanisms mediating the morning peak of plasma cortisol in man.

There is evidence for the existence of ACTH unrelated mechanisms in the regulation of cortisol secretion in man. This study was designed to elucidate the interrelationship between plasma ACTH and cortisol levels during the increase in cortisol levels, which occurs during morning hours. The results were compared with those of an artificial cortisol peak induced by administration of small amounts of ACTH, and with ACTH and cortisol values during insulin-induced hypoglycemia. In these control groups, the increase in cortisol levels was preceded by a large increase in ACTH levels; in the case of the physiological morning peak there was no adequate rise in mean ACTH levels. Thus, the spontaneously occurring increments in individual ACTH levels appear to be inappropriate for the increases in cortisol. This conclusion was corroborated by the finding that oscillations of plasma cortisol concentrations, comparable to the physiological morning peak, were demonstrable in ACTH-deficient patients when they were supplied with subthreshold amounts of exogenous ACTH. These findings argue against the classic concept that the adrenal cortex is invariably linked to immediately preceding episodes of pituitary ACTH secretion.

Adrenal Cortex↗
PubMed1983

The meal-related peak in plasma cortisol is not mediated by radioimmunoassayable ACTH.

There is evidence for the existence of ACTH-unrelated mechanisms in the regulation of cortisol secretion in man. The present study was designed to elucidate the interrelations between plasma ACTH and cortisol levels during the 'midday surge' in cortisol concentrations. For comparison, a 'midday surge' was imitated by infusing small amounts of ACTH in dexamethasone-suppressed subjects. The meal-related cortisol bursts were not preceded by an adequate increase in ACTH levels. In contrast, markedly elevated ACTH levels were necessary to produce a comparable cortisol peak by administration of ACTH. Apparently, the meal-related bursts in cortisol levels were not mediated by radioimmunoassayable ACTH. These findings argue against the classic concept that the adrenal cortex is inseparably linked to immediately preceding hormonal events occurring in the hypothalamo-pituitary system.

Adrenocorticotropic Hormone↗