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Biomedical subjects

H G Dörr

Publications and source records attributed to H G Dörr.

At least 19 recordsLinked to original sources
PubMed2006

No evidence for angiotensin type 2 receptor gene polymorphism in intron 1 in patients with coarctation of the aorta and Ullrich-Turner syndrome.

In male patients with congenital anomalies of the kidney and urinary tract, an increased incidence of a polymorphism in the angiotensin type 2 receptor gene (AT2R) has been identified. The AT2R has been shown to be involved in apoptosis, particularly during embryogenesis. The aim of this study was to examine the A-->1675G transition polymorphism in intron 1 of the AT2R gene that is located on the X chromosome in patients with coarctation of the aorta (CoA) with and without Ullrich-Turner syndrome (UTS). Screening of DNA samples was performed with restriction fragment length polymorphism analysis. Ninety-seven patients with CoA, 28 girls with UTS, 10 girls with UTS and CoA, and 96 control individuals were studied. There was no significant difference in the distribution of A and G-genotypes in any of the patient groups compared to controls. An A-->1675G transition in the AT2R gene seems not to be involved in the pathogenesis of aortic coarctation.

Aortic Coarctation↗
PubMed2005

Molecular features and clinical phenotypes in androgen insensitivity syndrome in the absence and presence of androgen receptor gene mutations.

Androgen insensitivity syndrome (AIS) is characterized by deficient or absent virilization in 46,XY individuals despite normal or even elevated androgen levels. AIS is usually caused by mutations in the androgen receptor (AR) gene. We aimed at contrasting clinical, biochemical, and molecular genetic characteristics of three patients (P1-P3) with clinically evident partial (P1) and complete (P2, P3) AIS with and without AR gene mutations. AR expression was studied in cultured genital skin fibroblasts (GSF) by Western immunoblotting, ligand binding analyses, Northern blotting, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), and RT-PCR spanning exons 1-8. AR gene DNA sequence was analyzed by single-strand conformation analysis (SSCA), and DNA sequencing. GSF revealed reduced (P1) or absent (P2, P3) ligand binding. Northern blots showed either slightly reduced hybridization of the 10.5-kb AR transcript (P3) or no hybridization (P1, P2), as confirmed by semiquantitative RT-PCR. RT-PCR spanning exons 1-8 detected single AR mRNA bands in P1-P3 excluding splicing errors. Western analyses showed either low (P1) or no (P2, P3) AR protein. While SSCA initially did not reveal any molecular abnormality, sequencing showed a novel CAG (Gln) to TAG (stop) mutation at codon 59 (P3) and a previously described 2-bp deletion at codon 472, leading to a frameshift and premature stop in codon 499 (P2). Intriguingly, P1 showed an unaltered DNA sequence of the coding region of the AR gene including all intron-exon boundaries. In conclusion, patients with clinically evident complete AIS are likely to harbor an AR gene mutation, demanding that the two polymorphic regions must always be included in molecular analyses of the AR gene. Moreover, our data support the concept that in a subset of AIS patients, particularly those with partial AIS, molecular alterations outside the coding region of the AR gene must be presumed.

Androgen-Insensitivity Syndrome↗
PubMed2005

Serum cortisol and cortisone levels in newborns with congenital adrenal hyperplasia before the start of therapy.

Sodium loss in infants with salt wasting (SW) congenital adrenal hyperplasia (CAH) does usually not occur within the first week of life. We hypothesized that sufficient mineralocorticoid activity might by temporarily maintained by still appropriate concentrations of cortisol. Plasma samples were obtained from 15 infants with SW-CAH before the onset of sodium loss, 17 patients with simple virilizing (SV)-CAH and 28 healthy infants under 14 days of age. Plasma aldosterone concentrations were significantly lower in SW-CAH infants than in SV-CAH patients and in healthy neonates. Plasma cortisol levels and cortisol/cortisone (F/E) ratios in SW-CAH patients were almost the same as in the SV-CAH and control group. While declining plasma aldosterone levels precede the onset of SW in CAH patients, plasma cortisol concentrations are kept normal in SW-CAH infants, temporarily maintaining sufficient mineralocorticoid activity.

Adrenal Hyperplasia, Congenital↗
PubMed2005

Spontaneous prolactin secretion in growth hormone-deficient children.

OBJECTIVE: To establish the spontaneous nocturnal prolactin (PRL) release in relation to growth hormone (GH)-deficient children and idiopathic short-stature children (ISS). METHODS: A total of 32 prepubertal children (11 girls, 21 boys) aged between 3 and 12 years were studied retrospectively and sorted according to diagnosis: idiopathic GH deficiency (GHD, n = 9), neurosecretory deficiency of GH secretion (NSD, n = 10) and ISS (n = 13). Nocturnal spontaneous hormone secretion was studied by intermittent venous sampling. Secretion profiles and copulsatility were analyzed using Pulsar and AnCoPuls software. RESULTS: (median, range in mug/l): Children with GHD and NSD had significantly lower GH and area-under-the-curve (AUC) levels than normal children (p < 0.001), whereas ISS children showed normal values. In contrast, prolactin levels were significantly higher (p < 0. 05) in children with GHD and NSD (11.1, 4.9 - 13.0 and 10.3, 8. 8 - 19. 6, respectively) compared to the ISS children (8.0, 4.9 - 13.0). In addition, prolactin AUC and peak height were higher (p < 0.05) in GH-deficient patients, whereas all other secretion parameters were the same. Correlation and copulsatility analysis revealed no evidence for a direct relation between PRL and GH secretion. CONCLUSIONS: PRL secretion is significantly higher in children with GHD and NSD compared to ISS children but PRL and GH show no copulsatile secretion pattern.

Child↗
PubMed2003

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.

Adolescent↗
PubMed2002

[Resistance to thyroid hormone - goiter and attention deficit-hyperactivity disorder as main manifestation].

HISTORY AND CLINICAL FINDINGS: Two siblings with goiter and attention deficit-hyperactivity disorder were presented. Earlier laboratory tests showed increased serum levels of thyroid hormones in association with non-suppressed serum levels of thyrotropin (TSH) in both children. Because hyperthyroidism caused by inappropriate secretion of thyrotropin was suspected, a cerebral MRI was performed. A pituitary adenoma was excluded in both children. Before antithyroid drug treatment was initiated, both patients were referred to our hospital. Careful medical history, clinical examination of the patients and careful interpretation of the laboratory results finally led to the diagnosis resistance to thyroid hormone (RTH). INVESTIGATIONS: Thyroid hormone serum levels were elevated in both children, while serum TSH was within the normal range. Molecular analysis confirmed the diagnosis of RTH. COURSE: Thyrostatic treatment was not initiated. CONCLUSION: Careful medical history, correct interpretation of laboratory results, comprehensive clinical examination and molecular genetic analysis are important in the diagnosis of RTH.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Behavioral evaluation of GH treatment in short statured children and adolescents: findings from a pilot study.

A cohort of 93 short-statured children and adolescents undergoing GH treatment were evaluated with respect to behavior, emotions, and attitudes. The sample consisted of patients suffering from either idiopathic GH deficiency or neurosecretory dysfunction (no.=47), Turner syndrome (no.=20), organic GH deficiency due to brain tumors (no.=10), or other etiologies (no.=16). The Child Behavior Checklist (CBCL) together with a brief Evaluation of Treatment Questionnaire (ETQ) were filled out by the patient's parents. These evaluations were performed at onset and after 12 and 24 months of GH treatment, respectively. There was a highly significant but clinically small decline of behavioral abnormalities over time and parents saw major benefits of GH treatment in the total group of patients. The behavioral changes over time were independent of diagnostic category, gender, height velocity, puberty and age.

Adolescent↗
PubMed2002

Spontaneous nocturnal leptin secretion in children with myelomeningocele and growth hormone deficiency.

OBJECTIVE: To examine the spontaneous leptin secretion in patients with myelomeningocele (MMC) and growth hormone deficiency (GHD). METHODS: Serum leptin levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 +/- 0.5 years), 10 patients with idiopathic GHD (IGHD; CA 7.6 +/- 0.7 years) and 12 children with normal variant short stature (NVSS; CA 7.6 +/- 0.5 years). Mean BMI (kg/m(2)) values of the groups did not differ significantly. Nocturnal leptin levels were analyzed over 10 h (blood samples every 20 min) and measured by specific radioimmunoassay. RESULTS: Mean leptin concentrations did not correlate with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was significantly different to those of children with IGHD and NVSS. Morning leptin levels did not decline as observed in both other groups. CONCLUSION: Since all groups were matched for BMI values, we suggest a hypothalamic dysregulation of leptin secretion in MMC patients.

Body Composition↗
PubMed2001

First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation.

Deletions within HSA band 4p16.3 cause Wolf-Hirschhorn syndrome (WHS), which comprises mental retardation and developmental defects. A WHS critical region (WHSCR) of approximately 165 kb has been defined on the basis of 2 atypical interstitial deletions; however, genotype-phenotype correlation remains controversial, due to the large size of deletion usually involving several megabases. We report on the first known patient with a small de novo interstitial deletion restricted to the WHSCR who presented with a partial WHS phenotype consisting only of low body weight for height, speech delay, and minor facial anomalies; shortness of stature, microcephaly, seizures and mental retardation were absent. The deletion was initially demonstrated by FISH analysis, and breakpoints were narrowed with a "mini-FISH" technique using 3-5 kb amplicons. A breakpoint-spanning PCR assay defined the distal breakpoint as disrupting the WHSC1 gene within intron 5, exactly after an AluJb repeat. The proximal breakpoint was not found to be associated with a repeated sequence or a known gene. The deletion encompasses 191.5 kb and includes WHSC2, but not LETM1. Thus, manifestations attributable to this deletion are reduced weight for height, minor facial anomalies, ADHD and some learning and fine motor deficiencies, while seizures may be associated with deletions of LETM1.

Abnormalities, Multiple↗
PubMed2001

Phaeochromocytoma associated with a de novo VHL mutation as form fruste of von Hippel-Lindau disease.

UNLABELLED: Phaeochromocytomas usually occur sporadically but may be associated with dominant inherited cancer syndromes such as multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau disease (VHL) and type 1 neurofibromatosis. We report on a boy presenting at age 8 years with an isolated benign phaeochromocytoma of the left adrenal. Three years later a second adrenal phaeochromocytoma was diagnosed on the right side and removed. His family history was negative. Genetic analysis did not show a mutation in the MEN 2 susceptible proto-oncogene rearranged during transfection; however, we found a germline missense mutation in the VHL gene (nucleotide 695 G to A transversion) which has been described only twice before in the literature. Both parents had normal (wild type) VHL copies indicating that our patient had a de novo germline VHL mutation. Careful clinical evaluation of the patient at 18 years did not reveal any other manifestations of VHL disease. CONCLUSION: Carriers of von Hippel-Lindau germline mutations can present with a form fruste of von Hippel-Lindau disease presenting initially with unilateral phaeochromocytoma and therefore mutation analysis should be carried out.

Adrenal Gland Neoplasms↗
PubMed2001

Homocysteine concentrations in a German cohort of 500 individuals: reference ranges and determinants of plasma levels in healthy children and their parents.

Elevated plasma homocysteine is a risk factor for cardiovascular disease and a sensitive marker of inadequate vitamin B12 and folate status. We studied 257 pupils (120 boys, 137 girls, aged 6-17 years) and their parents (88 males, 172 females, aged 26-50 years). Our measurements were part of a national Bavarian health and nutrition examination survey evaluating cardiovascular risk factors. A mild hyperhomocysteinemia (Hcys >15 micromol/l) occurred in 7% of the adults, but in none of the children. Men had significantly higher Hcys levels than women (p<0.0001), boys and girls had comparable concentrations. For adults and children, Hcys correlated inversely with vitamin B12 and folate and positively with the lean body mass and creatinine in serum, but not with cystatin C. Genetic and nutritional factors are determinants of Hcys metabolism. The correlation of Hcys and serum creatinine is dependent on the metabolic link between Hcys production and creatine synthesis.

Adolescent↗
PubMed2001

Relationship between salivary progesterone, 17-hydroxyprogesterone, and cortisol levels throughout the normal menstrual cycle of healthy postmenarcheal girls.

OBJECTIVE: To determine the usefulness of salivary P and 17 alpha-hydroxyprogesterone (17-OHP) for the assessment of ovarian function. In addition, salivary cortisol (F) levels were measured to assess the role of the adrenal cortex throughout the menstrual cycle. DESIGN: Prospective study. SETTING: Outpatients in hospital for children and adolescents. PATIENT(S): Thirty young women with regular menstrual cycles. INTERVENTION(S): Saliva collection in the early morning from day 1 of menstrual bleeding until next menses. MAIN OUTCOME MEASURE(S): Salivary P, 17-OHP, and F measured by RIAs. RESULT(S): During days 1-12 of the follicular phase, P and 17-OHP levels remained unchanged (P: 9-29.3 pg/mL; 17-OHP: 8-31 pg/mL). Thereafter, P increased exponentially from day 13 onward, reaching a plateau (mean +/- SEM, 70.1 +/- 9.0 pg/mL) between day 16 and 20, followed by a constant decrease until end of the cycle. The 17-OHP levels increased between day 14 and 17 (maximum: 45.8 +/- 4.5 pg/mL), decreasing rapidly thereafter. The F levels remained unchanged (follicular: 7.5 +/- 1.1 ng/mL; luteal 7.2 +/- 1.1 ng/mL). There was a significant correlation between P and 17-OHP (r(2) = 0.43; P<.001). When calculating ratios of P/F and 17-OHP/F, linear regression yielded a much stronger correlation (r(2) = 0.74; P<.001), although F did not show any correlation to P or 17-OHP. CONCLUSION(S): Changes in salivary 17-OHP levels throughout the menstrual cycle reflect ovarian but not adrenal function.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Stability of salivary steroids: the influences of storage, food and dental care.

We studied influences of dental care, food and storage on the reproducibility of salivary steroid levels. Cortisol (F), 17OH-progesterone (17OHP) and Progesterone (P) were measured using adapted commercial radioimmunoassays. Saliva samples of healthy adults (n = 15; m:8; f:7) were collected directly before and after dental care, and directly before and after breakfast with various foodstuffs. A second experiment investigated stability of steroids under different storage conditions. Four series of identical saliva portions (I: Native saliva; II: Centrifuged saliva; III: Saliva with trifluor acetate (TFA); IV: Saliva with 0.5% NaN(3)) were stored at room temperature and at 4 degrees C for up to three weeks. To demonstrate influences of repeated thawing and re-freezing of saliva on steroid values, saliva samples (n = 15) were divided into identical portions. These portions were frozen and re-thawed up to 5 times before measurement. Neither dental care nor intake of bread or milk effected the reproducibility of F, 170HP, and P. Steroid levels decreased significantly in the course of three weeks under different storage conditions (P < 0.001). This decrease was clinically relevant from the second week onward, with exception of NaN(3) treated samples. After repeated freezing and re-thawing 17OHP and P decreased slightly (about 5%). Only F decreased significantly after the third thawing (P < 0.001). The results show the usefulness of standardized handling of saliva samples for improving reproducibility and reliability of salivary steroid measurements.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Effect of glucocorticoid excess on the cortisol/cortisone ratio.

OBJECTIVE: The conversion of cortisol, which binds avidly to the mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid function, is predominantly catalyzed by the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2). It was the objective of the present study to examine the impact of different forms of glucocorticoid excess on the cortisol/cortisone ratio and to differentiate their role in the genesis of hypertension. DESIGN AND METHODS: Plasma cortisol and cortisone levels were determined in 12 adults with Cushing's disease, 12 adults with hypercortisolism due to an adrenal tumor, and 20 healthy volunteers before and after an intravenous ACTH test, using specific radioimmunoassays after automated Sephadex LH 20 chromatography. RESULTS: The cortisol/cortisone ratios were significantly higher in patients with Cushing's disease (13.9 +/- 1.1), adrenal tumors (11.5 +/- 2.3), and in healthy volunteers after ACTH stimulation (14.1 +/- 2.0) than in untreated controls (6.0 +/- 0.5) (P < 0.001, P < 0.05, and P < 0.001, respectively). Similar differences were seen for cortisol plasma concentrations, whereas cortisone concentrations did not differ among the groups. CONCLUSIONS: Our data suggest that the excessive mineralocorticoid effects in patients with hypercortisolism are inflicted by elevated cortisol/cortisone ratios possibly due to an insufficient conversion of cortisol to cortisone by 11beta-HSD 2. This may provide a possible explanation for the occurrence of hypertension. This effect seems to be independent of the role of ACTH in the mechanism of hypercortisolism.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Hypercalcemia and idiopathic hypoparathyroidism.

Idiopathic primary hypoparathyroidism (prHP) is a rare disorder and clinical experience of its management is limited. Prolonged immobilization of such patients can cause hypercalcemia and hypercalciuria. We report on a boy with prHP who developed hypercalcemia and renal failure as a result of calcium and calcitriol substitution not being stopped while he was immobilized for 2 months. Any substitution in patients with prHP must be stopped during prolonged immobilization. Laboratory monitoring is mandatory during this period.

Calcium↗
PubMed2001

A cross-sectional study of dehydroepiandrosterone sulfate in prepubertal children with myelomeningocele.

OBJECTIVE: To assess biochemical characteristics of adrenarche in patients with myelomeningocele (MMC), we examined serum levels of dehydroepiandrosterone sulfate (DHEAS) in prepubertal MMC patients. PATIENTS AND METHODS: The study included a total of 54 prepubertal patients with MMC and shunted hydrocephalus: 13 patients (2 m, 11 f; aged 4.6-10.1 years, mean 8.1 +/- 0.4) with isolated pubarche (Tanner stage PH 2-4, B1 or testes volume < or =3 ml) and 41 prepubertal MMC patients without pubarche (17 m, 24 f; aged 2.0-11.9 years; mean 6.8 +/- 2.5). DHEAS levels were measured directly by chemiluminescence immunoassay (Nichols, USA). Auxological data (supine length, body mass index (BMI), arm span) and bone age (BA) were recorded. RESULTS: (mean +/- SD): Basal DHEAS levels correlated with chronological age (CA) (r = 0.32, p < 0.05), BA (r = 0.65, p < 0.01; n = 23), BMI (r = 0.54, p < 0.01) and pubic hair stage (PH1 vs. PH2-4, r = 0.49, p < 0.01). 10/11 patients aged 2-4 years had DHEAS levels in the normal range, whereas 18/40 (45.0%) of the 5- to 9-year-old patients showed elevated levels (>+2 SDS). Ten patients with isolated pubarche (10/13; 2 m, 8 f; CA 8.3 +/- 1.5 years) and 9 patients without pubarche (9/41; 6 m, 3 f; CA 6.9 +/- 2.1 years) had elevated DHEAS levels (+6.34 and +4.05 SDS, respectively). The values correlated with BA/CA ratio (p < 0.05, n = 23). There was a trend to higher BMI SDS levels in patients with elevated DHEAS levels. CONCLUSION: Our data show an early and increased activation of adrenal androgen secretion in MMC patients.

Aging↗
PubMed2001

Identification of leptin in human saliva.

Leptin is produced predominantly in adipose tissue but has recently also been found in gastric mucosa. It has been shown that the oral application of leptin induces neuronal activity in the brain stem of rodents. The objective of the present study was to identify this hormone in human saliva and to examine the production and stability of salivary leptin. We have demonstrated production of leptin in salivary glands and oral mucosa by RT-PCR, its storage by immunocytochemistry, and the release of the peptide by RIA. Chromatographic analysis and immunoblotting confirmed the identity of leptin. There is a strong linear correlation (r2 = 0.78) between leptin concentrations from simultaneously collected saliva and plasma samples (n = 61). Stimulation of saliva flow increases total leptin secretion up to 3-fold (P < 0.001). As to the stability of leptin in gastric fluid, we found the peptide was not degraded above pH 3.5. Additionally, salivary leptin remains stable up to 5 d at 4 C. With regard to the presence of leptin receptors in gastric mucosa, we suggest salivary leptin as being a possible ligand for gastric leptin receptors. Furthermore, the determination of leptin in saliva allows for noninvasive sample collection.

Adult↗