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R Finke

Publications and source records attributed to R Finke.

At least 19 recordsLinked to original sources
PubMed2004

[Metformin, an efficacious drug in the treatment of polycystic ovary syndrome].

BACKGROUND AND OBJECTIVE: Polycystic ovary syndrome (PCOS), with an incidence of 5% in women of reproductive age, is defined as the presence of oligo- or amenorrhea in combination with hyperandrogenism. Most patients also suffer from impaired insulin action (insulin resistance). PCOS thus resembles the metabolic syndrome (type 2 diabetes mellitus, hypertension, lipid disorders, atherosclerosis). International studies showed a beneficial effect of metformin treatment on biochemical and reproductive parameters in PCOS. The aim of our study is the evaluation of metformin treatment in a German PCOS sample. PATIENTS AND METHODS: 103 PCOS women (age 18-40) were treated, according to their body weight, with either 1000 mg or 1700 mg metformin per day after assessment of insulin resistance. Clinical features as well as endocrine and metabolic parameters were recorded at baseline and at 1, 6, and 12 months of treatment. Additionally, baseline data were compared with those of 98 control subjects (age 18-38). RESULTS: PCOS women showed significantly higher body mass index, body fat mass and androgen levels, as well as an impaired glucose- and insulin metabolism compared to controls. Metformin treatment ameliorated acne (36% to 4%), hirsutism-score (11.2 to 9.7) and restarted normal menstrual cycles in 66.7% of PCOS-women. Sixteen of 48 patients with unfulfilled wish to conceive became pregnant during therapy. Metformin restored menses in all previously amenorrheic women. Comparing post-metformin versus baseline levels, HOMA-IR (4.6 to 2.3), AUC-I (379 to 225) and 2-h glucose (117 to 90 mg/dl) decreased significantly. Furthermore, metformin decreased testosterone (2.9 to 1.8 nmol/l), free androgen index (9.1 to 5.3) and dehydroepiandrosterone levels (5.1 to 3.9 mg/l). CONCLUSION: Metformin improves significantly hyperandrogenism and insulin resistance in PCOS patients and appears to be an efficacious mode of therapy.

Adolescent↗
PubMed2003

High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

PURPOSE: Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. PATIENTS AND METHODS: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. RESULTS: The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. CONCLUSION: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

Adolescent↗
PubMed2000

[Ultrasound characterization of burn scars in children].

So far, little is known about the acoustic phenomena of high-frequency sonography for the assessment of healing processes in thermal wounds. However, ex vivo investigations have shown clear age-dependent differences in the rate of sound propagation in thermal scars compared to healthy skin. In order to answer the question of whether measurable acoustic characteristics of burn or scald scars can be classified in a way which corresponds to the clinical severity of the injuries, age of scar or type of treatment, 92 thermal scars, with an average scar age of 3.1 years, in 55 children were investigated with regard to corium thickness and echogenicity. A control group of 25 non-injured children of similar age was studied for comparison. It was shown that measurable echogenicity differences can allow conclusions about clinical severity to be drawn. The comparison of different therapeutic strategies showed no therapeutic effect either for compression or for the application of silicone gel sheets. In contrast, a decrease in scar thickness and a loosening of scar structure could be seen after early application of a sterile, silicone-covered polyamide net bandage. The 20-MHz-Sonography is a suitable non-invasive procedure for the characterisation of burn scars.

Age Factors↗
PubMed1999

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗
PubMed1997

Ectopic intrathyroidal thymus diagnosed as a solid thyroid lesion: case report and review of the literature.

The authors report a case of a 6-year-old boy in whom aberrant thymic tissue was misdiagnosed as an intrathyroidal solid lesion. The patient underwent hemithyroidectomy and did well. Because cervical ectopic thymus rarely produces symptoms, the true incidence in children is unclear. Surgeons need to consider this rare entity, not to mistake it as a thyroid neoplasm, and not to perform extensive thyroid resection.

Child↗
PubMed1997

Polymorphisms of TAP1 and TAP2 genes in Graves' disease.

Graves' disease is an autoimmune disorder in which HLA DQA1*0501 and DQB1*0201 confer predisposition. The genes for transporters associated with antigen processing (TAP1 and TAP2) locate near to HLA DQ coding regions and display only a limited degree of polymorphism. Since polymorphisms of TAP might influence susceptibility to Graves' disease by a possibly different selection of antigenic peptides, we investigated sequence variants of TAP1 and TAP2 genes in 235 patients with Graves' disease and 218 random healthy controls by polymerase chain reaction (PCR) followed by sequence specific oligonucleotide analysis (SSO), single strand conformational polymorphism (SSCP) analysis and amplification refractory mutation system (ARMS). TAP1*0301 (Val-333/Asp-637: 71% vs. 55% in controls, p < 0.008, RR = 2.05) and TAP2*0101 (Val-379/Ala-565/Thr-665/stop-687: 83% vs. 69% in controls, p < 0.03, RR = 2.20) showed a positive association with Graves' disease whereas TAP1*0401 a negative (Ile-333/Gly-637: 4% vs. 13% in controls, p < 0.01, RR = 0.25). After selection of patients and controls for HLA DQA1*0501 a similar association was found for TAP1*0301 (72% vs. 50% in controls, p < 0.02, RR = 2.63) and TAP1*0401 (4% vs. 16% in controls, p < 0.04, RR = 0.22), when matching for HLA DQB1*0201 as well as for TAP1*0401 (3% vs. 16% in controls, p < 0.05, RR = 0.18). Our findings indicate that the positive association of TAP1*0301 and the negative of TAP1*0401 with Graves' disease cannot only be explained by linkage disequilibrium between TAP alleles and HLA DQ. Therefore, these TAP alleles contribute to genetic susceptibility in Graves' disease as additional permissive and protective factors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus.

The genetic susceptibility to Graves' disease and type 1 (insulin-dependent) diabetes mellitus is conferred by genes in the human leukocyte antigen region on the short arm of chromosome 6, but several other genes are presumed to determine disease susceptibility. Among those candidate genes is the cytotoxic T lymphocyte antigen 4 (CTLA4) located on chromosome 2q33 in man. We investigated the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in Graves' disease and IDDM. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, single strand conformation polymorphism, and restriction fragment length polymorphism analysis in 305 patients with Graves' disease, 293 patients with IDDM, and 325 controls. Patients with Graves' disease had significantly more Ala alleles than controls, both as homozygotes (21% vs. 13%) and as heterozygotes (53% vs. 46%), and less Thr as homozygotes (26% vs. 42%; P < 2 x 10(-4). The phenotypic frequency of Ala-positive patients (73%) was significantly higher than of controls (58%; P = 10(-4); relative risk = 2). Patients with IDDM also had significantly more Ala alleles as homozygotes (19%) or heterozygotes (50%; P = 0.01). In conclusion, an alanine at codon 17 of CTLA4 is associated with genetic susceptibility to Graves' disease as well as to IDDM.

Abatacept↗
PubMed1997

Codon 17 polymorphism of the cytotoxic T lymphocyte antigen 4 gene in Hashimoto's thyroiditis and Addison's disease.

Endocrine autoimmune disorders share susceptibility and resistance factors of the human leukocyte antigen system on the short arm of chromosome 6, but other gene loci also contribute to predisposition and protection. Because the cytotoxic T lymphocyte antigen 4 (CTLA4) alanine-17 encoded by the CTLA4 gene on chromosome 2q33 confers susceptibility to Graves' disease, as well as to type 1 (insulin-dependent) diabetes mellitus, we investigated this dimorphism in the other endocrine autoimmune disorders: Hashimoto's thyroiditis and Addison's disease. We analyzed the CTLA4 exon 1 polymorphism (49 A/G) in 73 patients with Hashimoto's thyroiditis, 76 with Addison's disease, and 466 healthy controls. This dimorphism corresponds to an aminoacid exchange (Thr/Ala) in the leader peptide of the expressed protein. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism analysis, and restriction fragment length polymorphism analysis using BbvI. Patients with Hashimoto's thyroiditis had significantly more Ala alleles than controls, both as homozygotes (22% vs. 15%) and heterozygotes (53% vs. 46%), and less Thr than controls as homozygotes (25% vs. 39%), P < 0.04. The phenotypic frequency for Ala was significantly higher in patients (75%), compared with controls (61%), P < 0.03. Patients with Addison's disease did not differ significantly from controls, but those carrying the suceptibility marker, human leukocyte antigen DQA1*0501, were significantly more CTLA4 Ala17 positive than controls with the same DQA1 allele (P < 0.05). In conclusion, an alanine at codon 17 of CTLA4 confers genetic susceptibility to Hashimoto's thyroiditis, whereas this applies only to the subgroup of DQA1*0501+ patients with Addison's disease.

Abatacept↗
PubMed1997

Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors.

This study reports the development of a highly sensitive and reproducible RIA for the measurement of 3,5-diiodothyronine (3,5-T2) in human serum and tissue. The RIA employs 3-bromo-5-[125I]iodo-L-thyronine (3-Br-5-[125I]T1) as tracer, which was synthesized carrier free by an interhalogen exchange from 3,5-dibromo-L-thyronine (3,5-Br2T0). The detection limits were 1.0 fmol/g and 0.8 pmol/L in human brain tissue and serum, respectively. T3, diiodothyroacetic acid, and 3-monoiodothyronine cross-reacted with a 3,5-T2 antibody to the extent of 0.06%, 0.13%, and 0.65%, respectively. Serum concentrations of 3,5-T2 were measured in 62 healthy controls and 4 groups of patients with nonthyroidal illness, i.e. patients with sepsis (n = 24), liver diseases (n = 23), head and/or brain injury n = 15), and brain tumors (n = 21). The mean serum level of 3,5-T2 in the healthy subjects was 16.2 +/- 6.4 pmol/L. Concentrations of 3,5-T2 were significantly elevated in patients with sepsis (46.7 +/- 48.8 pmol/L; P < 0.01), liver diseases (24.8 +/- 14.9 pmol/L; P < 0.01), head and/or brain injury (24.1 +/- 11.3 pmol/L; P < 0.05), and brain tumors (21.6 +/- 4.8 pmol/L; P < 0.01). In all 4 patient groups, serum levels of T3 were significantly reduced, confirming the existence of a low T3 syndrome in these diseases. Serum concentrations of 3,5-T2 were significantly elevated in patients with hyperthyroidism (n = 9) and were reduced in patients with hypothyroidism (n = 8). The levels of T4, T3, and 3,5-T2 were measured in normal human tissue samples from the pituitary gland and various brain regions and in brain tumors. In normal brain tissue, the concentrations of 3,5-T2 ranged between 70-150 fmol/g, and the ratio of T3 to 3,5-T2 was approximately 20:1. In brain tumors, however, T3 levels were markedly lower, resulting in a ratio of T3 to 3,5-T2 of approximately 1:1. Recent findings suggest a physiological, thyromimetic role of 3,5-T2, possibly stimulating mitochondrial respiratory chain activity. Should this prove to be correct, then the increased availability of 3,5-T2 in nonthyroidal illness may be one factor involved in maintaining clinical euthyroidism in patients with reduced serum levels of T3 during nonthyroidal illness.

Astrocytoma↗
PubMed1997

Myxedema.

This review will discuss generalized myxedema as it develops in hypothyroidism. First, the precipitating conditions (thyroprivic trophoprivic + goitrous forms) and the clinical manifestations of thyroid hormone deficiency are presented. Pathobiochemical and pathophysiological factors that lead to the main manifestations include retention of fluid, retention of sodium and hyponatremia. In particular are primary and direct consequences of reduced thyroid hormone levels, and secondary or indirect consequences, such as cardiovascular and renal derangements. In hypothyroidism many biochemical disturbances result. Most important is the interstitial deposition of hydrophilic mucopolysaccharides, which in turn lead to fluid and Na retention and impairment of blood circulation and lymphatic drainage. Myxedema, therefore, is to a large extent a lymphatic edema. Hyponatremia is an indirect consequence of the lack of T3 and is directly caused by impaired renal Na reabsorption. Renal Na,K-ATPase is reduced in specific segments. The often discussed role of inappropriate elevation of circulating ADH does not seem to be a key factor in myxedema. Impaired capacity of renal water excretion is caused by reduced GFR. We discuss the time dependent development of the derangement of different organ systems, and include recently published biochemical results, according to which the lack of T3 interferes not only with the metabolism of numerous compounds of the interstitial matrix, but also with cell surface proteins and intracellular proteins of microfilaments. Finally, we refer briefly to pretibial myxedema in states of hyperthyroidism, that is, infiltrative dermopathy in Graves' disease, which is caused by poorly understood autoimmune processes.

Animals↗
PubMed1996

Theoretical basis and application of molecular diagnostics.

Molecular biology has brought much progress in understanding physiology and pathophysiology as well as tumor development in thyroidology. The principles of gene organisation, regulation, and expression will be mentioned in regard to the thyroid and thyroid hormones. A growing number of thyroid disorders are linked to molecular events like mutations, deletions, splice errors, gene duplications or aberrant expression. The genetic causes and molecular approaches in diagnosis are most evident in rare inheritable syndromes, such as familial medullary thyroid carcinoma (FMTC, MEN 2), thyroid hormone resistance or non-autoimmune autosomal dominant hyperthyroidism. Furthermore, in toxic nodules, papillary and sporadic medullary thyroid carcinomas somatic mutations have been found, of which the pathogenetic role is still under debate. The molecular tools to diagnose gene mutations are mostly based on the polymerase chain reaction (PCR). Screening methods include single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), and temperature gradient gel electrophoresis (TGGE). More specific methods like enzyme restrictions or allele-specific PCR require precise knowledge of the mutation which is searched for in genomic DNA. DNA sequencing is the safest but not the cheapest or simplest way to detect a mutation. Some examples will be given for the application of the above mentioned methods in diagnosing certain thyroid diseases.

Gene Expression Regulation↗
PubMed1995

Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis.

It is unknown whether in chronic lymphocytic thyroiditis the goitrous (Hashimoto's thyroiditis) and atrophic forms (primary myxedema) are variants of the same disease or different pathogenic entities. Conventional thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytotoxic events induce gland atrophy and thus should be detectable more often in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with autoimmune thyroiditis, using a 51chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Other thyroid-specific antibodies, like TSH binding-inhibiting antibodies, TSH function-blocking antibodies, thyroglobulin antibodies and thyroid peroxidase antibodies, were determined. Cytotoxic antibody activity was 20.5% (median, range 0-54.5%) in patients with autoimmune thyroiditis and 8.3% (median, range 0-18.4%) in controls (p < 0.0001). Analysis of cytotoxicity regarding thyroid size showed a high incidence of cytotoxic antibodies in atrophic disease (median thyroid volume 6 ml), where cytotoxic antibodies were detectable in 80% versus 39% (x2 = 9.6; p < 0.0001) in goitrous disease (median thyroid volume 36 ml). The specific lysis of 30% (median; 95% confidence limit 23.9-32.9) in non-goitrous thyroiditis patients was significantly higher than in goitrous patients (16.9%; 95% confidence limit 13.2-20.4) (p = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Clinical experience with the Apnea Check System in screening for sleep apnea].

We examined 17 patients (3 female, 14 male) of 40 to 60 years of age suspected of suffering from sleep apnoea (SA) according to anamnesis and pulse oximetry, using the apnoea check system (AC) and by polysomnography (PS). AC measures the flow at the mouth and nose by means of thermistors and records the apnoea number, maximal duration of apnoea, and mean duration of apnoea (A mean). The PS-measured values: apnoea index (AI), maximal duration of apnoea (A max) and mean duration of apnoea (A mean) were taken to be equal to 100% and the AC-measured values were referred to these. AI (AC) was 76-577% of AI (PS). In 3 patients, AI (AC) was smaller than AI (PS), whereas in 14 patients it was greater. A max (AC) was 83-390% of A max (PS). In 11 patients A max (AC) was greater than A max (PS) and in 6 patients it was smaller. A mean (AC) was 56-223% of A mean (PS). In 9 patients A mean (AC) was greater and in 8 patients smaller than A mean (PS). PS had in 15 patients an AI > 10, in 2 patients < 10. In all patients, AC had an AI > 10. AC enabled identification of all patients suffering from sleep apnoea, and hence it appears to be suitable for screening. Further measurements in patients with AI < 10 will be necessary to examine the specificity.

Adult↗