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Biomedical subjects

W Winkelmann

Publications and source records attributed to W Winkelmann.

At least 145 records · Page 8Linked to original sources

Gel chromatographic characterization of immunoreactive adrenocorticotropin in patients with ACTH hypersecretion.

We investigated the molecular size of circulating immunoreactive ACTH by gel chromatography in patients with ACTH hypersecretion due to various disorders of the hypothalamic-pituitary-adrenal axis. 4 patients with Addison's disease, 2 with Nelson's syndrome, 4 with Cushing's disease, 6 with the ectopic ACTH syndrome (2 bronchial carcinoma, 1 medullary carcinoma, 1 metastatic islett cell carcinoma, 1 benign bronchial carcinoid and 1 patient with occult ectopic Cushing's syndrome) and 1 patient with hypersecretion of ACTH from a clinically nonfunctioning pituitary adenoma were studied. Analysis of the molecular size of immunoreactive ACTH was performed by gel chromatography on a Sephadex G-75 column (superfine, 100 x 1.5 cm) equilibrated with 1% formic acid. 2 ml fractions were collected and evaporated to dryness. The ACTH content of the recovered samples was determined by RIA. In Addison's disease, Nelson's syndrome and Cushing's disease the plasma showed a single peak of ACTH immunoreactivity at the expected position of 1-39 ACTH. In the ectopic ACTH syndrome the plasma of 4 patients revealed at chromatography at least one other peak eluting between the void volume and 1-39 ACTH suggestive of a high molecular weight form of ACTH whereas plasma of 2 patients showed only a single ACTH peak at the position of labeled 1-39 ACTH. The patient with a clinically non-functioning pituitary adenoma revealed a gel filtration pattern similar to the patients with ectopic ACTH syndrome and secretion of high molecular weight ACTH. We conclude that secretion of high molecular weight forms of ACTH is not a unique feature of the ectopic ACTH syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH Syndrome, Ectopic↗

[Diagnosis and therapy of asymptomatic adrenal tumors].

Adrenal tumours had been discovered incidentally (since 1981) in 32 patients (23 females and nine males; mean age 54 [25-73] years) who had had computed tomography (CT) or ultrasonography for other reasons: none had a history or symptoms of such tumour. Tumours were bilateral in eight, right or left-sided in 12 each: all had been confirmed by CT. Average tumour size was 3 cm (1-9 cm). Three patients had cortisol-producing adrenal tumours, and there was one benign phaeochromocytoma (abnormally high adrenaline and noradrenaline excretion). Fine-needle biopsies in two patients revealed a benign histology. An adrenalectomy was performed in eight patients (the one phaeochromocytoma, six adenomas and one ganglioneuroma). Follow-up CT in 11 of the non-operated patients 6-48 months later (mean of 14 months) did not demonstrate any increase in tumour size so that a waiting attitude seems justified: benign tumours are clearly much more frequent than malignant ones. However, if the tumour diameter is greater than 6 cm, an adrenalectomy is indicated because of the danger of malignancy.

Adenoma↗

[Treatment of metastatic adrenal carcinoma with suramin].

A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment.

Adrenal Cortex Neoplasms↗

Management and efficacy of intensified insulin therapy--starting in outpatients.

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6% +/- 2.4% to 8.0% +/- 1.3% (mean +/- SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients.

Blood Glucose↗

A rare tumor at the elbow: a glomangioma. Differential diagnosis and therapy.

Referring to a case of a glomangioma at the elbow, several aspects of this tumor are illustrated. Since the related hemangiopericytoma can be distinguished from the glomangioma by its biological behavior, the morphological differential diagnosis of both tumors is discussed in detail. Therapeutic consequences of one or the other diagnosis are also indicated.

Aged↗

Vasoactive intestinal peptide receptor regulation of cAMP accumulation and glycogen hydrolysis in the human Ewing's sarcoma cell line WE-68.

This study describes functional characteristics of receptors for vasoactive intestinal peptide (VIP) on human Ewing's sarcoma WE-68 cells. These characteristics include 125I-VIP binding capacity, cellular cAMP generation, glycogen hydrolysis, and pharmacological specificity. Binding studies with 125I-VIP showed specific, saturable, binding sites for VIP in WE-68 cells. Scatchard analysis revealed the presence of a single class of high-affinity binding sites that exhibited a dissociation constant (Kd) of 90 pM and a maximal binding capacity (Bmax) of 24 fmol/mg of protein. VIP and VIP-related peptides competed for 125I-VIP binding in the following order of potency: human (h) VIP greater than human peptide with N-terminal histidine and C-terminal methionine (PHM) greater than chicken secretin much greater than porcine secretin. Glucagon and the C-terminal fragments VIP[10-28] and VIP[16-28] and the VIP analogue (D-Phe2)VIP did not inhibit 125I-VIP binding. Addition of hVIP to WE-68 cells provoked marked stimulation of cAMP accumulation, hVIP stimulated increases in cAMP content were rapid, concentration-dependent, and potentiated by 3-isobutyl-l-methylxanthine (IBMX). Half-maximal stimulation (EC50) occurred at 150 nM hVIP. The ability of hVIP and analogues to stimulate cAMP generation paralleled their potencies in displacing 125I-VIP binding. (D-Phe2)VIP, VIP[10-28], VIP[16-28], and (p-Cl-D-Phe6, Leu17)VIP, a putative VIP receptor antagonist, affected neither basal cAMP levels nor hVIP-induced cAMP accumulation. WE-68 cell responses to hVIP were desensitized by prior exposure to hVIP. Desensitization to hVIP did not modify the cAMP response to beta-adrenergic stimulation, and beta-adrenergic agonist desensitization did not modify responses to hVIP. hVIP also induced a time- and concentration-dependent hydrolysis of 3H-glycogen newly formed from 3H-glucose in WE-68 cultures. hVIP maximally decreased 3H-glycogen content by 36% with an EC50 value of about 8 nM. The order of potency of structurally related peptides of hVIP for stimulation of glycogenolysis correlated with their order of potency for inhibition of 125I-VIP binding. IBMX potentiated the glycogenolytic action of hVIP and PHM. The simultaneous presence of the calcium channel antagonist verapamil or the calcium ionophore A 23187 did not influence the glycogenolytic and cAMP stimulatory effects of hVIP. Collectively, these data indicate that Ewing's sarcoma (WE-68) cells are endowed with genuine VIP receptors which are coupled to the formation of cAMP that probably serves a second messenger role in stimulating glycogen hydrolysis in these cells in response to VIP.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclic AMP↗

[Possibilities of sonography in the diagnosis of instabilities of the shoulder joint].

We present ultrasound investigation as a diagnostic tool for shoulder instability. The following structures are visible in the posterior transversal plane: subcutis, deltoid muscle, infraspinatus muscle, infraspinatus tendon, humeral head, scapula, dorsal glenoid rim, dorsal labrum, and the joint capsule. The relation of the humeral head to the glenoid can be judged statically and dynamically. Anterior and posterior instabilities and secondary signs of dislocation such as Hill-Sachs lesion and effusion can be seen. This technique is easy to learn. By comparing the injured with the normal shoulder the examiner can control his diagnosis. There is no need for positioning the patient in a special way. Sonographic evaluation is non-invasive and inexpensive.

Humans↗

[The value of sonography in assessing intracompartmental pressure in the anterior tibial compartment].

Fifty recreational athletes were subjected to a defined exercise programme (running on a treadmill, 8 km/h). The pressure in the middle third of the anterolateral compartment was measured. We also assessed the geometry and the echogenicity in the transversal and the longitudinal plane by sonographic means. The increase of the intracompartmental pressure increased as the ap-diameter of the compartment in the transverse plane increased (distance = superficial fascia - interosseous membrane). We found a correlation factor of 0.79. The echogenicity increased as the intracompartmental pressure increased. The changing ultrasound reflex pattern is considered non-reproducible because there are too many artifacts, nor is the increase in the ap-diameter due to the low correlation.

Adolescent↗

[Ultrasound determination of the humerus retrotorsion angle. An experimental and clinical study].

We examined the value of ultrasound to determine the retroversion of the humerus in an experimental and clinical study. In twenty human upper arms of corpses the retroversion angle was measured by ultrasound and by direct means using a paralellograph. The angle was also evaluated by sonography and CAT scan in 7 patients, and in 6 patients by sonography and x-ray. There was a poor correlation between sonographic measurement and direct measurement, CAT scan, or x-ray. Hence, we do not recommend sonography as a useful tool in preoperative planning. For this purpose, CAT scan or x-ray should be preferred. However, sonography may be useful for screening.

Chronic Disease↗

[The value of sonography in injuries of the knee joint].

In an experimental study we examined three knee specimens with regard to the value of ultrasound for imaging soft tissue structures. Subsequently we documented artificial lesions at the menisci and ligaments. With this experience we started a prospective study comparing the preoperative ultrasound investigation with the results of arthroscopy in 101 patients. For ultrasound evaluation we used a 5 MHz linear and a 7.5 MHz sector scanner. In the experimental as well as in the clinical study the menisci were well visualised. For medial meniscus lesions the accuracy and the predictive value was 81%. For the lateral meniscus the predictive value was 80%, although there was only an accuracy of 7% because of a large number of false positive results. We were not able to reliably detect cruciate ligament ruptures. However, ultrasound was useful to visualise Baker's cysts, bursitis, and jumper's knee.

Arthroscopy↗

Diagnosis and therapy for a leiomyosarcoma of vascular origin.

A case of a leiomyosarcoma of vascular origin in the left calf is presented. Because of the rarity of occurrence, some clinical aspects, and in particular, diagnostic procedures and therapy for the tumor, are discussed along with a review of recent literature.

Aged↗

The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease.

UNLABELLED: We investigated the effect of sodium valproate on plasma ACTH and serum cortisol concentrations in different pathological states of ACTH hypersecretion. Five patients with pituitary dependent Cushing's syndrome, two patients with Nelson's syndrome and five patients with Addison's disease were studied. Neither a single dose nor long term administration of sodium valproate resulted in a significant decrease of plasma ACTH levels in patients with Cushing's disease and Nelson's syndrome. Furthermore, the response of ACTH and cortisol to stimulation with lysine-vasopressin was unaffected during acute and chronic treatment. Patients with Addison's disease showed a slight attenuation of the ACTH response to lysine-vasopressin as compared to placebo but the difference was not statistically significant. IN CONCLUSION: sodium valproate does not appear to be effective in controlling ACTH hypersecretion in pituitary dependent Cushing's syndrome.

Addison Disease↗

Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in Cushing's syndrome.

We determined the adrenostatic potential of low-dose nonhypnotic etomidate in six patients with Cushing's syndrome (ectopic Cushing's syndrome, n = 2; Cushing's disease, n = 3; bilateral adrenal adenoma, n = 1). Etomidate was given as a continuous infusion for 32 h in a dose of 2.5 mg/h (n = 5) or 0.3 mg/kg/h (n = 3), respectively. Saline was given during a control period. The responsiveness to exogenous ACTH was studied during placebo and 7 and 31 h after commencing etomidate by administration of 250 micrograms 1-24 ACTH i.v. Etomidate (2.5 mg/h) led to a consistent decrease in serum cortisol in all patients from a mean of 39.4 +/- 13.3 to 21.1 +/- 5.7 micrograms/dl after 7 h (P less than 0.05 compared with placebo). After 24 h cortisol was reduced further to a mean steady state concentration of 12.3 +/- 5.7 micrograms/dl (P less than 0.05). At the end of the infusion period the cortisol increase in response to ACTH was reduced but not abolished. In contrast, a dose of 0.3 mg/kg/h etomidate induced unresponsiveness of serum cortisol to exogenous ACTH within 7 h. However, sedation was observed in two out of three patients at this dose, while during etomidate in a dose of 2.5 mg/h no side effects were seen. We conclude that low-dose nonhypnotic etomidate reduces serum cortisol to within the normal range in patients with Cushing's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial.

The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3-year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewing's sarcoma of bone.

Adolescent↗

[A new surgical method in malignant tumors of the ilium].

During the growth period the triradiate cartilage forms a barrier to the intraosseous tumor growth. It is then surgically possible to remove the ilium at the triradiate cartilage and leave more than 2/3 of the acetabulum. After transposition of the remaining acetabulum to the lateral side of the sacrum the hip joint can be preserved with a very good functional result.

Acetabulum↗