PubMed Health⌕ Search

Biomedical subjects

E Kauf

Publications and source records attributed to E Kauf.

At least 19 recordsLinked to original sources
PubMed2006

Elevated serum insulin-like growth factor binding protein-2 is associated with a high relapse risk after hematopoietic stem cell transplantation in childhood AML.

Insulin-like growth factor binding protein (IGFBP)-2 has mitogenic effects in normal and neoplastic cells. The purpose of this study is to examine the diagnostic and prognostic significance of elevated IGFBP-2 levels in children with AML after hematopoietic stem cell transplantation (HSCT) at relapse and continuous complete remission (CCR). In 27 children with AML (mean age 13.6+/-5.3 years; patients in remission n=15 with relapse n=12) serum parameters of IGFBP-2, IGFBP-3, IGF-I and IGF-II were analyzed up to 18 months after HSCT by RIA. AML-patients with evidence of relapse demonstrated a continuous increase of IGFBP-2 levels during the follow-up. At day 100 after HSCT, IGFBP-2 concentrations were significantly higher in patients with relapse than in children without relapse (7.4+/-4.0 standard deviation score (SDS) vs 3.9+/-1.7 SDS; P=0.01). Serum IGFBP-2 was identified as an independent factor for the prediction of relapse. Furthermore, the probability of relapse-free survival (RFS) in patients with IGFBP-2 >4.5 SDS at day 100 after HSCT was 31% compared to patients with IGFBP-2 <4.5 SDS was 72% (P=0.004). Patients with IGFBP-2 concentration up to 4.5 SDS more likely developed a relapse and had a poorer outcome. Identification of these patients allows a more individualized and aggressive adjuvant treatment and follow-up.

Adolescent↗
PubMed2005

[Assessment of skeletal age using a new ultrasound method].

PURPOSE: Determination of skeletal development in children is important. The most used evaluation method is to study left hand X-ray based on the standards depicted by Greulich and Pyle. The aim of our study was to compare the accuracy of a new sonographically based method with the standard method. MATERIAL AND METHODS: 160 consecutive evaluated children and adolescents (77 male, 83 female) who received a X-ray of the left hand were evaluated. Ultrasound examination of the same hand was performed on the same day using the BonAge system (Sunlight Medical Ltd., Israel). This system evaluates the relationship between the velocity of the wave (speed of sound) passing thorough the distal radial and ulna epiphysis and growth, using gender- and ethnicity-based algorithms. Three experienced investigators (U1-U3) analysed the X-ray and assigned bone age scores based on the Greulich and Pyle atlas (G and P). The investigators were blinded to the calendary age (CA) of the patient and also for the BonAge result. Correlation between BonAge system results and G and P was performed using SPSS 12.0.1. RESULTS: In 152 patients BonAge measurement could be performed successfully. The correlation between the three investigators using the G and P method was between 0.977 and 0.980; correlation between the BonAge system and the investigators (U1-U3) was 0.902 and 0.920. The paired t-test showed no significant differences between the BonAge system and the three investigators and also for the comparison between U1 and U2. There were significant differences between U1 vs. U3 and U2 vs. U3 (p < 0.05). DISCUSSION: The BonAge device demonstrates the ability to produce an sufficient assessment of bone age using an ultrasound method. The results are correlated with conventional skeletal age evaluation using the G and P method. Advantages of the ultrasound device are objectivity, lack of ionizing radiation, and easy accessibility. In the case of first investigation X-ray is necessary to look for dissociated skeletal age, dysplasia, and mineralisation.

Adolescent↗
PubMed2003

Recurrent vomiting and ethylmalonic aciduria associated with rare mutations of the short-chain acyl-CoA dehydrogenase gene.

We report identification of short-chain acyl-CoA dehydrogenase (SCAD) deficiency in a 12-year-old boy who suffered from recurrent attacks of vomiting once or twice a year from infancy. Growth and development were normal and there were no muscular symptoms. Metabolic screening was performed during a hospitalization at 8 years of age and revealed an increased excretion of ethylmalonic acid (EMA; 45-80 mmol/mol creatinine, normal 0.2-6.6), suggesting a degradation defect of short-chain fatty acids. An increased n-butyrylcarnitine was found in freshly collected serum (0.9 micromol/L; normal <0.4) but not in dry blood spots. Neither of the frequent SCAD gene variants 625G>A and 511C>T was present, but direct sequencing of the promoter and coding regions of the SCAD gene revealed that the patient had mutations on both alleles: 417G>C (Trpl15Cys) and 1095G>T (Gln341His). Neither mutation has been described before in compound heterozygosity or homozygosity. Enzymatic investigations subsequently confirmed a defect of SCAD in both fibroblasts and muscle extracts. Furthermore, expression studies of both mutations demonstrated impaired enzyme function or structure. To our knowledge, this case is the first description of a patient with proven SCAD deficiency presenting with recurrent emesis but without other symptoms, and emphasizes the wide clinical phenotype of this disorder.

Alleles↗
PubMed2003

Changes of serum growth factors (IGF-I,-II and IGFBP-2,-3) prior to and after stem cell transplantation in children with acute leukemia.

SUMMARY: Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) may play an important role in tumor proliferation. This study aimed to investigate the IGF system in children with acute leukemia prior to and after hematological stem cell transplantation (HSCT). In 51 patients (AML n=27; ALL n=24; mean age 11.2+/-4.8 years), serum parameters (IGF-I,-II, IGFBP-2,-3) were investigated up to 18 months after HSCT by RIA. Patients with AML showed a significant increase of IGFBP-2 up to 100 days after HSCT (mean +/-s.d. prior to HSCT: 3.2+/-3.6 SDS vs 100 days after HSCT: 5.3 degrees +/-3.4 SDS, P=0.005). Furthermore, IGF-I and IGFBP-3 were significantly decreased (IGF-I: -0.3+/-1.5 vs -0.7 +/-1.2 SDS, P=0.001; IGFBP-3: -0.3+/-1.1 vs -1.0+/-1.1 SDS, P=0.02). Children with AML showed significantly higher IGFBP-2 (P=0.04) and significantly lower IGF-I (P=0.03) and IGFBP-3 (P=0.05) levels than children with ALL at day 100 after HSCT. We conclude that children with acute leukemia show important changes in the IGF system after HSCT. In particular, IGFBP-2 was significantly elevated at day 100 after HSCT. Increased IGFBP-2 and decreased IGF-I and IGFBP-3 may be associated with the increased proliferation rate of transplanted bone marrow.

Adolescent↗
PubMed2001

Disturbed copper transport in humans. Part 1: mutations of the ATP7A gene lead to Menkes disease and occipital horn syndrome.

Mutations of the ATP7A gene (OMIM 300011) lead to the Menkes disease (MD, OMIM 309400) involving impaired brain development, neurological degeneration, connective tissue abnormalities, and high lethality in early infancy. Occipital horn syndrome (OHS, OMIM 304150), a milder phenotype, is also caused by ATP7A gene mutations. In MD patients, an early copper-histidine treatment may prevent the neurological impairment and prolong survival leading to an OHS phenotype. To demonstrate the genotype/phenotype correlation, two male patients are reported with different ATP7A gene mutations and several phenotypes. In the first patient with the MD phenotype, a mutation within the exon 20 (Gln1288Ter) was found producing a stop codon just prior to the highly conserved ATP binding domain. The OHS phenotype of the second patient was caused by a splice site mutation involving the position +6 of intron 6 within a copper binding domain. Small amounts of correctly spliced ATP7A transcript were sufficient to develop the milder OHS phenotype in this patient (OMIM 30001.0006). In conclusion, mutations of the copper transporting P-type ATPase ATP7A gene cause distinct human diseases showing some genotype/phenotype correlation and implications for treatment.

Adenosine Triphosphatases↗
PubMed2001

Disturbed copper transport in humans. Part 2: mutations of the ATP7B gene lead to Wilson disease (WD).

Mutations in the Wilson disease gene ATP7B, a P-type ATPase, are responsible for copper accumulation in the liver and other organs leading to Wilson disease (WD, OMIM 277900). Clinical manifestations of Wilson disease (WD) include chronic liver disease, acute hepatic failure or neuropsychiatric diseases. Since potent medical treatments are available to prevent disabling residual symptoms, early diagnosis is crucial. To demonstrate the clinical course and genetic findings, a male patient with a novel mutation in the ATP7B gene, a 10 base pair insertion in exon 6 (1927ins 10), and a second missense mutation in exon 13 (P992L) is reported. The patient presented with signs of chronic liver disease at the age of 10 years. Clinical findings included hepatomegaly, elevated liver enzymes and coagulopathy. A combination treatment with the copper chelating agent D-penicillamine and zinc acetate was started leading to normalization of liver function and no appearance of neurological signs or Kayser-Fleischer ring after 7 years follow-up. Truncating mutations of the ATP7B gene (insertions, deletions, nonsense mutations) leading to gross loss of C-terminal parts of the protein, thereby probably completely destroying the protein function, may correlate with a hepatic phenotype and early onset as seen in the patient presented.

Adenosine Triphosphatases↗
PubMed2000

Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH).

UNLABELLED: In 18 healthy women, the effect of two oral contraceptives (OCs) on insulin-like growth factor (IGF-I) and its binding protein-3 (IGFBP-3) and growth hormone (hGH) plasma level were studied before and after intake of either of two OC formulations over 21 days, one containing 2 mg dienogest and 0.03 mg ethinylestradiol (group A) and the other 0.125 mg levonorgestrel and 0.03 mg ethinylestradiol (group B). There was a reduction of the mean IGF-I concentration of 30% (p = 0.008) in the women receiving dienogest-containing pills and 12% (p = 0.006) in women taking the levonogestrel-containing preparation. This difference between drug groups was statistically significant (p = 0.002). A correlation between the control values and the basal-treatment difference (r = 0.945; p = 0.000) was observed only in women of group A. Between basal and treatment cycles the mean plasma levels of hGH remained unchanged in both groups tested, but the 23.5-h integrated mean hGH plasma concentrations (AUC(0-23.5h)) were significantly elevated by 36% (p = 0.016) in comparison to basal values before treatment only in women receiving the levonorgestrel-containing pills. Also, in the women who received the dienogest-containing preparation, the changes of integrated mean plasma level were inversely associated with the control values (r = -0.723; p = 0.025). Neither in group A nor in group B was the mean plasma level of IGFB-3 changed. IN CONCLUSION: the results of the present analysis indicate that hormonal contraceptives can modulate the GH and IGF-I-axis in the reproductive age. Probably the androgenic progestogen levonorgestrel (0.125 mg/day) opposes the estrogen-induced action. In the women who took the dienogest-containing formulations (anti-androgenic progestogen-group A), the extent of individual changes (hGh and IGF-I) depends on the basal level prior to pill intake. Further studies, especially of long-term intake of OCs, are necessary to confirm these results and to assess the practical relevance for possible effects on connective tissue and bone.

Contraceptive Agents, Female↗
PubMed2000

Insulin-like growth factor serum concentrations reflect insufficient growth in a hypoplastic infant with partial trisomy 9q in the 12th week of life.

This report presents changes of IGFs and IGFBPs in a female infant with partial trisomy 9q in the 12th week of life. Studying deficient growth in this hypoplastic infant (birth weight 1405 g, birth length 36 cm) with dysmorphic features, the following changes in IGFs and IGFBPs were detected (microg/l): IGF-I: 26.5 vs 48.1 in healthy infants; IGF-II: 420 vs 728; IGFBP-2: 931 vs 524; IGFBP-3: 800 vs 1070. This demonstrates that IGFs and IGFBPs may reflect individual insufficient growth even at this early age.

Adult↗
PubMed1998

[Gynecomastia in childhood. Pathological causes unusual but serious].

Enlargement of the breasts in males is known as gynecomastia, and represents a symptom that may be physiological (newborn, pubertal, senile gynecomastia), but may also have a pathological etiology (humoral disorders, side effects of medication, liver diseases, tumor disease). The physiological pubertal form occurs in approximately 40 to 60% of adolescents, usually resolves spontaneously within 2-3 years, and rarely requires treatment. Tumors of the breast in childhood are extremely rare. The diagnostic work-up must always aim at detecting possible underlying pathology, such as increased estrogen production, diminished androgen production, or androgen resistance. Since such a diagnostic investigation is complex, it should best be done by an experienced endocrinologist.

Adolescent↗
PubMed1998

Laparoscopy for Crohn's disease in children.

Traditionally, the diagnosis of Crohn's disease is established by colonoileoscopy and radiology. With these techniques the main area of interest, the distal ileum, is not easily reached. Also, the outer aspect of the bowel is ignored and there is no appreciation of the involvement of other intra-abdominal organs. Laparoscopy provides additional information. This may establish a more precise diagnosis, better standardization in comparative studies, and more specific therapy.

Adolescent↗
PubMed1998

Body weight distribution and organ size in newborn swine (sus scrofa domestica) -- a study describing an animal model for asymmetrical intrauterine growth retardation.

Normal growth is the expression of the genetic potential to growth which is neither abnormally constrained nor promoted by internal or external factors. Restricted fetal growth is common in human pregnancy and is associated with increased perinatal morbidity and mortality. Because of ethical restrictions, pathogenetical studies are necessarily dependent on appropriate animal models. In the studies presented, evidence will be provided that the naturally occurring distribution of body weight in newborn piglets, obtained from n = 512 newborn piglets (about 12 hours old) in 50 consecutive deliveries in the breed cohort of the mixed German domestic breed - "Deutsches Land-/Edelschwein" gives an appropriate sampling for providing a statistically reliable basis with which to determine different degrees of fetal growth for further pathophysiological studies intended. A strong inverse correlation (r = -0.66, p < 0.05) was found between the mean weight of the litter and the number of piglets per litter, and an inverse correlation (r = -0.64, p < 0.05) was found between the lowest weight of the littermate and the number of piglets per litter. Moreover, gravimetric investigations were made into an additional 53 one-day-old newborn piglets reflecting the naturally occurring birth weight distribution determined. A marked linear correlation between body weights and various organ weights was found (values of the correlation coefficient amounted to between 0.45 and 0.98; p < 0.05). The lowest variation of organ weights was found in the CNS structures (0.68-1.33). Skeleton and heart exhibited similar ranges of weight variation (0.35-1.81 and 0.38-2.00 of the means) to body weight (0.38-1.77 of the means). This was also expressed in the regression analysis, because the slope values were 0.99 and 0.97 respectively. The hormonal glands investigated, the kidneys, and the abdominal parenchymal organs exhibited the largest ranges of weight variation. Moreover, regression analysis gives evidence that the weight restriction was more pronounced than expected concerning respective body weight. This is indicated by slope values > 1 in almost all of those organs. Plasma concentration of IGF-1 showed an inverse correlation with body weight (r = -0.42; p < 0.05, fig 4). IGF-1 concentration of intrauterine growth retarded (IUGR) newborn piglets was in the mean nearly double that of normal weight animals (p < 0.05) and the brain weight to liver weight ratio was increased more than 2.5 times in IUGR newborn (fig 5 A, p < 0.05). This investigation provides information on the naturally occurring body weight distribution of one-day-old piglets, which was obviously a result of epigenetic factors. Gravimetrical estimation showed clearly that body weight variety is most probably caused by alterations of placental functioning. Severe alterations resulted in asymmetrical growth retardation, which was proved by a significantly increased brain to liver ratio in animals with a body weight < 10th centile. Thus, evidence is provided that naturally occurring asymmetrical intrauterine growth restricted newborn piglets can be identified simply by body weight measurement, so that convenient conditions are given for pathogenetically motivated studies on intrauterine compromised newborns.

Animals↗
PubMed1998

Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes.

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.

Adipocytes↗
PubMed1997

[Selenium in phenylketonuria patients. Effects of sodium selenite administration].

PATIENTS AND METHOD: 17 patients (8 female, 9 male; age 8.2 +/- 3.7 years) with phenylketonuria under phenylalanin restricted diet were investigated prior to and after 3 months of selenium substitution (sodium selenite, 115 micrograms Se/m2 BSA/d). Different parameters in blood were determined: selenium, glutathione peroxidase (Gpx) activity, thyroid hormones, blood cell count, lymphocytic antigen expression, muscle function and -enzymes, cardiac ultrasound. RESULTS: The main significant results of selenium substitution are: increased plasma-selenium, blood cell selenium, plasma-Gpx activity and left ventricular cardiac index as well as decreased plasma thyroxin, free thyroxin, reverse triiodthyronin, total cholesterol, mean erythrocyte and thrombocyte volume and lymphocytic CD2 expression. CONCLUSION: The data indicate metabolic and functional signs of selenium deficiency in patients with phenylketonuria without selenium substitution. We conclude that, despite of lacking clinical symptoms, a selenium supply in phenylketonuria patients under diet is necessary and should be performed with usefull peroral sodium selenite (115 micrograms Se/m2 BSA/d) initially, followed by a dosage between 30 and 60 micrograms Se/m2 BSA/d).

Antioxidants↗
PubMed1997

[Blood selenium content after conditioning and during the course of bone marrow transplantation in children with malignant diseases].

PATIENTS AND RESULTS: Prior to bone marrow transplantation (BMT), at the end of the conditioning phase, we found in 42 investigated children with malignant diseases subnormal lowered plasma- and blood selenium levels. Parallel to the diminished selenium status the plasma glutathione peroxidase activity (Gpx) was not reduced as it is in selenium deficiency, but markedly elevated and probably reflecting cytolytic processes. In the group of combined conditioning (fractionated total body irradiation plus chemotherapy) we found significantly more elevated plasma Gpx values in comparison to the only-chemotherapy group. The renal selenium excretion was elevated during the whole observation and could be caused by disturbed tubular function. CONCLUSION: We conclude, that in the situation of BMT a selenium substitution in a dosage of at least 1 to 2 micrograms Se/kg/d is necessary. Patients' selenium status should be monitored by analyses of plasma- and blood selenium contents.

Adolescent↗
PubMed1995

[The value of selenotherapy in patients with mucoviscidosis].

In cystic fibrosis (CF) patients the antioxidative-oxidative balance is chronically disturbed. Free radicals were generated by bronchial-pulmonal infection and additional exist a deficiency of antioxidative substances by enteral malabsorption especially vitamin E and selenium. Because selenium is an essential content of glutathione peroxidase, which is acting in cytosol and cell membranes, for the present we tested a selenium therapy (peroral sodium selenite 155 micrograms (Se/m2 BSA/d i. e. 4 micrograms Se/kg/d; 4 fold of recommended supply) in 32 CF patients. After three months of this therapy we have seen positive metabolic (normalized content of plasma-selenium, -glutathione peroxidase), endocrine (enhanced efficacy of thyroid hormones, mild increased IgF-I reduced LDL-chol) and clinical consequences (enhanced left ventricular cardiac output), but in three patients side effects (anorexia, nausea, mild hair loss) were observed. Longtime sodium selenite therapy only with 60 micrograms Se/m2 BSA/d over 1 year, stabilized the favourable influences without side effects. For CF patients therefore we recommend a sodium selenite substitution therapy, the best in combination with vitamin E.

Administration, Oral↗
PubMed1994

Sodium selenite therapy and thyroid-hormone status in cystic fibrosis and congenital hypothyroidism.

The effectiveness of a peroral sodium selenite therapy (115 micrograms Se/m2 BSA/d) administered to cystic fibrosis patients (n = 32) could after three months be identified in a significant serum selenium increase (0.69-->0.96 mumol/L), a significant malondialdehyde decrease (2.72-->1.64 mumol/L), as well as in a significant serum vitamin E increase (4.31-->5.72 micrograms/mL). Parallel to that, a serum T3 increase as well as a highly significant decrease in the serum T4/T3-ratio were found, too, which point to improved peripheral T4-->T3 conversion during selenium medication. Type-I-iodothyronine-5'-deiodinase has recently been identified as a specific selenoenzyme. In the case of congenital hypothyroidism (n = 37) application of sodium selenite in the above specified dosage yielded a mean serum selenium increase (0.87-->1.12 mumol/L), a not significant T3 increase (2.57-->2.61 nmol/L) as well as a not significant TSH decrease (5.34-->4.49 mIU/L) without an expected T4 decrease. With the serum lipids, however, a lowering of total cholesterol (4.85-->4.53 mmol/L) simultaneous with a mean increase in HDL-cholesterol (1.52-->1.66 mmol/L) as well as a decrease in LDL-cholesterol (2.93-->2.52) could be observed. We view the reduction of the atherogenic serum lipid constellation in the course of selenium medication as an expression of increased thyroid-hormone efficacy. Apart from an improvement of the antioxidant status a stimulation of thyroid-hormone efficacy owing to increased T4--T3 conversion is also noteworthy in sodium selenite medication.

Adolescent↗
PubMed1992

[Insulin-like growth factor I--a connecting link between nutrition and growth].

The influence of an increasing protein supply in combination with soybean oil upon the IGF-I concentration in the serum in correlation with growth was measured on 8 x 10 male Wistar rats. With a casein content of 0% in the food, the IGF-I level was 0.13 +/- 0.02 rU/ml. An IGF-I plateau of 0.74 +/- 0.07 rU/ml was reached at some 15% casein. The additional application of 3% soybean oil increased the IGF-I concentration significantly (P less than 0.01) up to 0.95 +/- 0.16 rU/ml. The investigations show a specific increase of the IGF-I synthesis by the addition of oil, which is paralleled by a further stimulation of the growth of the rats. The nutrition-dependent IGF production in the peripheral tissues (mainly liver) represents the connection link between the growth hormone axis (genetically potential growth) and the growth realizable depending on the supply with nutrients.

Animal Nutritional Physiological Phenomena↗