Search PubMed⌕ Search

Biomedical subjects

W Winkelmann

Publications and source records attributed to W Winkelmann.

At least 127 records · Page 7Linked to original sources
PubMed1993

[Rotation grafts].

Nowadays rotationplasty is well established as an acceptable procedure for limb salvage in patients who have a malignant tumor in the femur or tibia. The main indication is that it is the alternative to amputation. Rotationplasty should be used in very young children because of the growth-dependent complications that can be expected after tumor resection. The different types of rotationplasty, the operative technique, prosthetic care, and the results of 104 patients are shown.

Adolescent↗
PubMed1992

(Sub)periosteal Ewing's sarcoma of bone.

Ewing's sarcoma is a small malignant round-cell tumour that arises from mesenchymal cells, predominantly in the medullary cavity of bone. In exceptional cases it originates in the soft tissues and subsequently invades the underlying bone. A (sub) periosteal origin of Ewing's sarcoma is a very rare condition: only a few cases have been published so far. Three cases of (sub)periosteal Ewing's sarcoma, having received neoadjuvant chemotherapy and radiation therapy as well as wide excision, are reported.

Adolescent↗
PubMed1992

Type I and type II insulin-like growth factor receptors and their function in human Ewing's sarcoma cells.

Binding studies using recombinant human 125I-labelled insulin-like growth factor I ([125I]IGF-I) revealed IGF-I receptors in three Ewing's sarcoma cell lines with Kd ranging from 74 x 10(-12) M to 100 x 10(-12) M and Bmax = 36-63 fmol/mg cell protein. [125I]IGF-I binding was displaced by IGF-I, IGF-II and insulin with IC50 values of 1.5 nM, 6.3 nM and 0.7 microM respectively. Recombinant human [125I]IGF-II radioligand-binding assays in the cell lines disclosed specific binding sites for IGF-II with Kd = (110-175) x 10(-12) M and Bmax varying from 21 fmol/mg to 72 fmol/mg cell protein. Neither IGF-I nor insulin displaced [125I]IGF-II binding. IGF-I was found to increase basal glucose transport by maximally 1.5 times with EC50 = 0.9 nM IGF-I. The efficacy and potency of IGF-II on glucose uptake were comparable to those of IGF-I whereas insulin was ineffective. IGF-I and IGF-II also provoked stimulation of glycogen synthesis in Ewing's sarcoma cells. The maximal glycogenic response was reached at 0.01 microM IGF-I and 0.1 microM IGF-II, the EC50 value being approximately 1 nM IGF-I and 2 nM IGF-II. Insulin did not significantly influence glycogen formation. IGF-I and IGF-II but not insulin increased DNA synthesis in Ewing's sarcoma cells. The maximal mitogenic response was obtained with 10 nM IGF-I or IGF-II with an EC50 value of about 0.7 nM for both peptides. alpha-IR-3, a monoclonal antibody specific for the IGF type I receptor, effectively blocked IGF-I- and IGF-II-mediated metabolic responses. In conclusion, the data show that IGF-I and IGF-II induce rapid and long-term biological responses in Ewing's sarcoma cells exclusively through interaction with IGF type I receptors.

Antibodies, Monoclonal↗
PubMed1992

Expression of functional Y1 receptors for neuropeptide Y in human Ewing's sarcoma cell lines.

In the human Ewing's sarcoma cell line WE-68, saturation analysis using 3H-labelled neuropeptide Y ([3H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (Kd) of 4.5 nM and maximal binding capacity (B(max)) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors with Kd varying from 3.5 nM to 10.7 nM and B(max) = 247-3744 fmol/mg cell protein. NPY, its natural analogues and the Y1-receptor-specific peptide ligand [Leu31,Pro34]NPY inhibited [3H]NPY binding in the potency order: [Leu31,Pro34]NPY greater than or equal to human NPY greater than or equal to peptide YY (PYY) greater than salmon pancreatic polypeptide (PP) greater than human PP greater than porcine NPY13-36 much greater than NPY22-36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [32P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess Gi-protein-coupled NPY receptors of the Y1 type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.

Adult↗
PubMed1992

Osteonectin in osteosarcomas: a marker for differential diagnosis and/or prognosis?

Seventy-five osteosarcomas at various grades of histologic differentiation were investigated for evidence of osteonectin. According to the results of the study, osteonectin was present in all osteosarcomas. An association between the intensity of the osteonectin antibody reaction and prognosis could not be established. Evidence of osteonectin was also found in other bone tumors. Osteonectin is therefore unsuitable for differential diagnosis, cannot be regarded as a bone specific protein and has not prognostic value.

Biomarkers, Tumor↗
PubMed1992

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.

Adrenal Gland Neoplasms↗
PubMed1992

In vitro effects of tumor necrosis factor-alpha on human thyroid follicular cells.

Tumor necrosis factor-alpha is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-alpha with an average of 9,300 receptors/cell (Kd = 1.9 x 10(-10) mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-alpha resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613 +/- 7,989 cpm under basal conditions to 63,326 +/- 6,822 cpm after 100 U/l tumor necrosis factor-alpha (p < 0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-alpha. The maximum effect was observed after 1,000 U/l tumor necrosis factor-alpha (281.5 +/- 107.0 vs 114.5 +/- 33.6 fmol cAMP/micrograms protein under basal conditions: p < 0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-alpha binding. We conclude that in vitro tumor necrosis factor-alpha modulates in addition to its well known synergistic effect on interferon-gamma induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.

Adult↗
PubMed1991

Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86.

The Cooperative Ewing's Sarcoma Studies, CESS 81 and CESS 86, are multiinstitutional trials with more than 80 participating institutions from Germany, the Netherlands, Austria, and Switzerland. Treatment consists of four courses of multiagent chemotherapy and local therapy. Local therapy was not randomized and was either radical surgery or resection plus postoperative irradiation or definitive radiation therapy. Here results according to local therapy have been analyzed for 93 protocol patients with localized Ewing's sarcoma (ES) who have been recruited in CESS 81 from January 1981 to February 1985 and 122 protocol patients recruited in CESS 86 from January 1986 to November 1989. The 3-year relapse-free survival (RFS) was 55% in CESS 81 and 62% in CESS 86. In CESS 81, the RFS was better for surgically treated than for irradiated patients. In this study there was an extremely high incidence of local failures (50%) after definitive irradiation. In CESS 86, however, the results after radiation therapy have been improved markedly (3-year RFS 67% after radiation therapy, 65% after surgery, and 62% after resection plus irradiation). Possible explanations for the improvement of radiotherapeutic results are as follows: selections for patients for radiation therapy, start of local therapy, and quality of radiation therapy. In CESS 86, irradiated patients were randomized to receive either conventionally fractionated irradiation with less intense chemotherapy or hyperfractionated irradiation with simultaneous chemotherapy. There was no difference in treatment results at the time of analysis. The authors conclude that selection of patients for local treatment modalities and quality of treatment performance has an impact on local and overall treatment results in ES.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Ultrasound documentation of translational movement of the shoulder joint. Normal values and pathologic findings].

In a prospective study we evaluated diagnostic ultrasound investigation for shoulder instabilities. In 150 healthy persons we measured the passive ap-translation in relation to the dorsal glenoid as well as the inferior subluxation in relation to the acromion. After establishing normative data we measured 23 patients with unidirectional instabilities and 34 with multidirectional instabilities. The humeral head position of a normal joint is 8 to 10 mm dorsally to the glenoid. In the control group, the anterior translation of the dominant shoulder (Student-t test p = 0.0045) was significantly higher. Patients with anterior instabilities showed a significant increase of anterior translation in the injured shoulder (Student-T test; p = 0.0001). In comparison to the control group, there is a significant increase in downward subluxation in patients with multidirectional instabilities (chi2, alpha = 0.05). In habitual or voluntary dislocations, the relation of the humeral head to the glenoid can be judged statically and dynamically. Secondary signs of dislocation (Hill-Sachs lesions, joint effusion) are evident.

Adolescent↗
PubMed1990

Bilateral posterior pendulum dislocation of the shoulder. Case report and review of the literature.

A 20-year-old patient with bilateral voluntary and involuntary dislocation of both shoulders is reported on. There was no history of significant trauma, no systemic hypermobility of joints, no signs of neurological or psychological problems, and no evidence of joint disease. According to Reischauer's classification of shoulder instabilities, the patient suffered from bilateral posterior pendulum dislocations of his shoulders. The literature is reviewed and different classifications of shoulder instability and the underlying pathology of voluntary and involuntary shoulder dislocations are discussed. After ruling out the possibility of psychological problems, we performed an operative stabilization by arthroscopic means. At 1-year follow-up the patient reported no recurrence, good shoulder musculature, and no disability at work. This result confirms the unsuspicious psychological evaluation and our therapeutic management.

Adult↗
PubMed1990

[Possibilities of sonography in patellar apex syndrome].

23 Patients suffering from jumper's knee were examined by sonography. Using ultrasound imaging, we demonstrated pathologic changes in the tendon. Reproducible documentation of the patella tendon was proved by using three specimens. In a control group of 110 normal objects normative values for the size and structure of the tendon were documented. We present a classification using ultrasound patterns. With this classification the diagnosis becomes objective and reproducible. The physician can decide which conservative therapy is appropriate to this state of the disease, the surgeon gets information for the operation, and the success of the therapy can be documented.

Adolescent↗
PubMed1990

Diurnal salivary cortisol patterns during pregnancy and after delivery: relationship to plasma corticotrophin-releasing-hormone.

The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.

Adult↗
PubMed1990

A multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of patients with Cushing's disease.

Bilateral, selective, and simultaneous catheterization of the inferior petrosal sinus is not only a valuable tool in the differential diagnosis of Cushing's syndrome, but may also provide new insights into paracrine interactions at the pituitary level. We have investigated whether CRH (1 microgram/kg BW) has any effect on the release of PRL, GH, TSH, or the alpha-subunit of hCG during this procedure. Sixteen patients under evaluation for Cushing's syndrome (Cushing's disease, n = 12; ectopic ACTH syndrome, n = 2; glucocorticoid resistance, n = 1; hormonally inactive adenoma, n = 1) were catheterized. Two of the patients with Cushing's disease received 4.0 mg naloxone iv 15 min before stimulation with CRH. Patients with Cushing's disease demonstrated a central/peripheral gradient and an intersinus gradient not only for ACTH, but also for PRL, alpha-subunit, GH, and TSH, provided that the latter two hormones were not completely suppressed by the glucocorticoid excess. Moreover, all hormones increased in response to CRH on the side with the highest ACTH concentration; PRL rose from 31.2 +/- 6.4 to 61.6 +/- 12.4 micrograms/L (P less than 0.01), and alpha-subunit from 2.6 +/- 0.6 to 6.4 +/- 1.7 micrograms/L, (P less than 0.01). Naloxone was unable to abolish the PRL or alpha-subunit increase in response to CRH. A multihormonal response to CRH in inferior petrosal sinus blood was also observed in the patient with glucocorticoid resistance and in the patient with the hormonally inactive tumor, but not in the patients with ectopic ACTH secretion. The multihormonal response to CRH could be explained by cosecretion of other hormones together with ACTH from corticotroph adenoma, by an effect of CRH on pituitary blood flow, or by a paracrine action of pituitary corticotrophs on adjacent normal pituitary cells. Our results do not support the concept that such a paracrine action is mediated by beta-endorphin. However, a higher dose of naloxone may be required to antagonize the action of pituitary beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1990

[The disease picture of melorheostosis].

The rare syndrome of Lér's melorheostosis is described on the basis of a case encountered in one of our own patients, a 29 year old male patient. Particular attention is given to the symptoms, the specific results of clinical examination, and the differential diagnosis.

Adult↗
PubMed1989

[Recent aspects of the pathogenesis of endocrine autoimmune diseases in the human: what role does expression of class II HLA molecules in the endocrine target cell play?].

The inappropriate expression of HLA Class II molecules by the target cells of endocrine autoimmune diseases is a recent observation that has been intensively studied in thyroid autoimmunity and type I diabetes mellitus. In vitro studies have shown that interferon-gamma can induce Class II expression, either alone, as in thyrocytes, or in combination with other mediators like tumour necrosis factor or lymphotoxin, as in islet cells, pointing to possible mechanisms operating in vivo. Endocrine cells expressing Class II molecules are able to present their autoantigens to helper T cells, thus possibly inducing the autoimmune process. However, until now it is still unclear if the expression of Class II molecules by the target cells is the primary immune phenomenon, which might possibly be triggered by a latent viral infection of the endocrine cell. Alternatively, it might be a secondary response in an ongoing autoimmune process. Particularly data obtained in the diabetic pancreas favour the first possibility, but only progress in our understanding of the role of HLA antigens in immunoregulation will make it possible to interpret the phenomenon properly.

Autoimmune Diseases↗
PubMed1989

Cardiac function in endocrine diseases: I. Acromegaly.

The aim of our echocardiographic study was to characterize cardiac function and anatomy of 14 acromegalics (A: 9 women, 5 men; mean age: 42.4 yrs) more closely. The duration of acromegaly in 4 of these patients was between 3 and 12 years; the disease was diagnosed for the first time in the other patients. Double M-mode echocardiography was performed in all patients and the results compared with data obtained from a control group of 24 healthy volunteers (N: 22 men, 2 women; mean age: 23 yrs). The mean left ventricular diameter at end-diastole was greater in the acromegalics than in the controls (A: 55 +/- 6 mm, N: 50 +/- 4 mm; p less than 0.005, means +/- SD). After correction for age and body surface area, it, however, was outside the 95% confidence interval in 5 patients. Left ventricular hypertrophy was present in 3 patients, one of whom had coexistent arterial hypertension. A total of 3 patients were hypertensive. Significantly higher values for the maximal velocity of systolic wall thickening (A: 6.1 +/- 0.6 cm/s, N: 4.2 +/- 0.6 cm/s, p less than 0.001) and diameter change (A: 12.4 +/- 2.0 cm/s, N: 10.6 +/- 1.0 cm/s, p less than 0.005) indicate increased contractility with concurrently increased relaxation; fractional shortening did not differ significantly (A: 38 +/- 5%, N: 37 +/- 5%, ns). The isovolumetric relaxation period at diastole was slightly longer in the acromegalics (A: 70 +/- 17 ms, N: 61 +/- 13 ms, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗