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Biomedical subjects

W Jeske

Publications and source records attributed to W Jeske.

At least 37 records · Page 2Linked to original sources
PubMed1997

MRI versus CT in the diagnosis of Nelson's syndrome.

The purpose of the study was to evaluate the utility of MRI and CT in the diagnosis of Nelson's syndrome, i. e. pituitary tumours in patients bilaterally adrenalectomized for Cushing's disease. Thirteen patients, followed up for 5-29 years after adrenalectomy, were studied. In 6 of them CT and MRI revealed no changes in the pituitary gland. In the remaining 7 patients only three CT scans were suggestive of a pituitary adenoma. MRI studies with administration of gadodiamide confirmed the CT diagnosis of Nelson's tumour in 3 patients and disclosed microadenomas in a further 4 patients. Neurosurgical treatment in 4 patients confirmed the MRI findings. Additionally CT and MRI examinations were performed in 5 patients suspected of a recurrent Nelson's tumour 3-11 years after neurosurgery. MRI visualized recurrent adenomas in 3 patients that were not well seen by CT scans. In our experience MRI was more effective than CT in the diagnosis of Nelson's syndrome.

Adrenalectomy↗
PubMed1997

Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients.

OBJECTIVE: Incidentally discovered adrenal masses are fairly common, although there are some controversies concerning the results of hormonal investigation (especially DHEAS values) and the methods of management. We summarize our experience in diagnosis, pathological findings and treatment of a large group of patients with incidentally found adrenal tumours. DESIGN AND PATIENTS: Our study included patients referred to the Department of Endocrinology of the Centre of Post-graduate Medical Education (Warsaw, Poland) during the last 10 years because of an adrenal tumour incidentally found on ultrasound scan. In all cases this was confirmed by computed tomography. There were 208 patients (148 female and 60 male), 14-76 years old. Unilateral adrenal masses were found in 172 patients (right 106, left 66), while bilateral masses were demonstrated in 36 patients. The size of the tumours ranged between 0.8 and 21.0 cm. The most common clinical abnormalities were hypertension (36 cases), obesity (23 cases), diabetes (8 cases), Addison's disease (6 cases). MEASUREMENTS: Endocrine tests evaluating pituitary-adrenal function (urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and catecholamines, plasma concentrations of ACTH, cortisol, DHEAS, androstendione and testosterone, dexamethasone suppression test and corticotrophin-releasing hormone stimulation test). RESULTS: Cortisol hypersecretion was noted in two patients with coexisting Cushing's disease and high normal 17-OHCS values with lack of dexamethasone suppressibility were found in six other patients with pre-clinical Cushing's syndrome. More common were subtle hormonal abnormalities: low ACTH levels (in 33 out of 98 investigated patients), diminished dexamethasone suppressibility and lack of ACTH response in the CRH test (in two out of 12 patients). Urinary catecholamine excretion was elevated in nine patients. In the group of 85 patients treated by surgery the most frequent pathological findings were: adrenocortical adenoma (21), carcinoma (17), phaeochromocytoma (13), metastatic masses (12) and myelolipoma (10). The size of carcinomas ranged from 3.2 to 20.0 cm, while the size of non-malignant tumours ranged from 1.5 to 21.0 cm. CONCLUSIONS: Every patient with an incidentally discovered adrenal mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment. Most of the adrenocortical carcinomas were > 7.0 cm in diameter. For prophylactic purposes, adrenal incidentalomas > 4.0 cm should be treated by surgery, while the smaller ones could be followed-up (with special care for those between 3.0 and 4.0 cm).

17-Hydroxycorticosteroids↗
PubMed1997

Biochemical and pharmacologic characteristics of Reviparin, a low-molecular-mass heparin.

The introduction of low-molecular-mass heparins (LMMHs) has added a new dimension to the prophylactic and therapeutic management of thromboembolic disorders. These agents are now globally accepted as drugs of choice for postsurgical prophylaxis of deep vein thrombosis (DVT). Currently, the LMMHs are being developed for various therapeutic and cardiovascular indications. Reviparin is an optimized LMMH prepared by controlled nitrous acid digestion of porcine mucosal heparin. This drug has been developed utilizing validated procedures and exhibits a relatively narrow molecular mass distribution in contrast to most other commercially available LMMHs. The specific activity in the anticoagulant assays is approximately 40 U/mg whereas the specific activity in amidolytic anti-Xa assays is approximately 100 anti-Xa U/mg. Reviparin is capable of producing dose- and time-dependent antithrombotic effects in animal models of thrombosis. Although ex vivo anticoagulant effects are initially observed at dosages that are antithrombotic, this agent has been found to produce sustained antithrombotic effects when ex vivo anticoagulant actions are not measurable. Repeated administration of this LMMH induces progressively stronger antithrombotic effects. This drug has also been found to release tissue factor pathway inhibitor (TFPI) following both intravenous (IV) and subcutaneous (SC) administration. The studies included in this article are designed to provide additional data on the molecular profile using new calibration methods and additional results on pharmacologic studies. In particular, the release of TFPI following IV and SC administration to nonhuman primates is described. The effect of repeated administration of Reviparin mimicking the postsurgical prophylaxis of DVT is also reported in terms of any augmentation of the antithrombotic or hemorrhagic effects of this agent.

Animals↗
PubMed1997

Low molecular weight heparins: a developmental perspective.

Low molecular weight heparins (LMWHs) are now universally accepted as drugs of choice for post-surgical prophylaxis of deep vein thrombosis (DVT). Currently these agents are also being developed for the treatment of thrombosis and various cardiovascular indications. Due to manufacturing differences, each of the LMWHs exhibits a distinct pharmacological and biochemical profile. The specific activity of these agents in the anticoagulant assays ranges from 35 - 45 anti-IIa U/mg, whereas the specific activity in terms of anti-Xa units is designated as 80 - 145 anti-Xa U/mg. These LMWHs are capable of producing product-specific dose- and time-dependent antithrombotic effects in animal models of thrombosis. While the ex vivo effects are initially present at doses that are antithrombotic, these agents have been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. In experimental animal models and in various clinical trials, these agents have also been found to release tissue factor pathway inhibitor (TFPI) after both iv. and sc. administration. Repeated administration of LMWHs produces progressively stronger antithrombotic effects; however, the haemorrhagic responses vary and are largely dependent on the product used. The release of TFPI following iv. and sc. administration in a primate model also demonstrates product individuality and the relevance of this inhibitor to the actions of LMWHs. Furthermore, repeated administration, mimicking the post-surgical prophylaxis of DVT, leads to product-based augmentation of the antithrombotic or haemorrhagic effects. Antithrombotic and haemorrhagic studies are discussed, comparing the pharmacological profile of some of the available LMWHs. Product individuality, in terms of relative potency in different assays and the failure of standardisation protocols to provide any guidelines for product substitution and prediction of the clinical effects, is also addressed.

Journal Article↗
PubMed1996

Early diagnosis of Nelson's syndrome.

Nelson's syndrome is a specific form of Cushing's disease treated by bilateral adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary adenoma (corticotropinoma). These ACTH-secreting tumors are frequently aggressive, so early diagnosis is of prime importance. We have studied 33 patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic hormone (ACTH) and cortisol measurements during routine hydrocortisone replacement therapy, computed tomography (CT), pituitary magnetic resonance imaging (MRI), and visual field examination. The results obtained in a group of six patients diagnosed in the last 3 yr were compared with those obtained in a group of 27 patients examined before 1992. High plasma ACTH levels accompanied by normal serum cortisol concentration were characteristic for a late stage of the disease. Absolute temporal scotomas were an early finding. MRI, especially with the gadolinium enhancement, was superior to CT in demonstrating pituitary microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early neurosurgical treatment of the patients with Nelson's tumors.

Adenoma↗
PubMed1996

Preclinical studies on a low molecular weight heparin.

Some major developments in the area of antithrombotic therapy have occurred during the past decade. Of these, the concept of fractionation of heparin has resulted in the development of several products from this agent. The introduction of low molecular weight heparins (LMWHs) has added a new chapter to the prophylactic and therapeutic management of thromboembolic disorders. These agents are now globally accepted as drugs of choice for post-surgical prophylaxis of deep vein thrombosis (DVT). Currently, the LMWHs are being developed for various therapeutic and cardiovascular indications. Reviparin is an optimized LMWH prepared by controlled nitrous acid digestion of porcine mucosal heparin. This drug has been developed using validated procedures and exhibits a relatively narrow molecular weight distribution in contrast to most other commercially available LMWHs. The specific activity in anticoagulant assays is approximately 32 U/mg whereas the specific activity in terms of anti-Xa units is 120 anti-Xa U/mg. Reviparin is capable of producing a dose- and time-dependent antithrombotic effect in animal models of thrombosis. While the ex vivo effects initially occur at dosages that are antithrombotic, this agent has been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. This agent has also been found to release tissue factor pathway inhibitor (TFPI) after both intravenous and subcutaneous administration. Repeated administration of reviparin produces progressively stronger antithrombotic effects. The current studies are designed to provide additional data on its molecular profile using new calibration methods and additional results on the pharmacological studies in a dose-dependent manner. In particular, the release of TFPI following i.v. and s.c. administration in a primate model is described. The effect of repeated administration mimicking the post-surgical prophylaxis of DVT is also reported in terms of any increase in the antithrombotic or haemorrhagic effects of this agent. Comparative antithrombotic and pharmacological studies are also reported to compare the pharmacological profiles of reviparin, nadroparin and enoxaparin.

Animals↗
PubMed1996

Pharmacological profiling of recombinant tissue factor pathway inhibitor.

Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine protease inhibitor found within the vascular system that is known to be released upon heparin administration. Tissue factor pathway inhibitor regulates the extrinsic pathway by inhibiting both factors VIIa and Xa. The role of TFPI in the prevention of thrombosis is currently being elucidated. These studies describe the pharmacological profile of recombinant variants of this inhibitor that have recently been made available for study. Recombinant TFPI (rTFPI) exhibits potent anticoagulant (PT) and antiprotease actions (anti-Xa). While carboxy truncated forms of the inhibitor were not observed to prolong the PT, potent anti-Xa effects were still noted. In a rabbit model of stasis-thrombosis, full-length rTFPI dose-dependently inhibited thrombus formation, producing a complete inhibition of thrombosis at a dose of 500 micrograms/kg. At doses that were antithrombotically effective, minor increases in blood loss were observed in a rabbit ear bleeding model. The effect of TFPI on the inhibition of platelet activation was assessed using a flow cytometric assay. Three hundred nmol/L of rTFPI were observed to block the activation of platelets by 4.5 pmol/L recombinant tissue factor. In addition to participating in the maintenance of hemostasis, rTFPI may prove to be an effective therapeutic modality for preventing thrombus formation.

Amino Acid Sequence↗
PubMed1996

Physical and pharmacologic manipulation of the vascular system as measured by the release of TFPI and other mediators of antithrombotic actions.

Utilizing highly sensitive monoclonal based assays, we have measured various mediators of antithrombotic action including t-PA, prostacyclin and tissue factor pathway inhibitor (TFPI). To evaluate the pharmacologic stimulation of these mediators, blood from patients treated with heparin and low molecular weight heparin in (LMWH) at various dosages, group of patients treated with oral polydeoxyribonucleotide (defibrotide), a synthetic analogue of heparin, namely aprosulate (Luitpold Pharma, Munich, Germany) were analyzed for various vascular mediators. Similarly, to evaluate patients treated with physical modalities such as the sequential compression devices alone and sequential compression devices in combination with LMWHs were tested for these same parameters. Heparin produced a marked release of TFPI and t-PA after i.v. administration. After subcutaneous administration, a relatively smaller elevation of these parameters were seen. Several of the LMWHs produced varying effects on the release of TFPI and t-PA and the area under the curve after the s.c. injection was found to be much higher than i.v. administration. Defibrotide administration after i.v. and oral administration also resulted in a significant increase in the TFPI and t-PA antigen levels. However, the prostacyclin metabolite 6-keto-PGF1 alpha was much higher than the values obtained the heparins. Repeated administration of a hypersulfated heparin analogue produced marked increase in TFPI in both i.v. and s.c. studies. These results indicate that besides directly acting on plasmatic mediators, antithrombotic drugs are capable of releasing endogenous mediators of antithrombotic actions. Physical manipulation of the vascular system can also produce these effects. Thus, both physical and pharmacologic means can be used to produce an antithrombotic state to mediate their prophylactic and therapeutic effects.

Anticoagulants↗
PubMed1996

Are the available low-molecular-weight heparin preparations the same?

Low molecular weight heparins (LMWHs) are now universally accepted as drugs of choice for post-surgical prophylaxis of DVT. Currently these agents are also being developed for therapeutic and cardiovascular indications. Because of manufacturing differences, each of the LMWHs exhibit distinct pharmacologic and biochemical profiles. The specific activity of these agents in the anticoagulant assays ranges from 35 to 45 anti-IIa U/mg whereas the specific activity in terms of anti-Xa units is designated as 80 to 120 anti-Xa U/mg. These LMWHs are capable of producing product specific dose and time dependent antithrombotic effects in animal models of thrombosis. While the ex vivo effects are initially present at dosages that are antithrombotic, these agents have been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. In the experimental animal models and in various clinical trials, these agents have also been found to release tissue factor pathway inhibitor (TFPI) after both intravenous (i.v.) and subcutaneous (s.c.) administration. Repeated administration of LMWHs produces progressively stronger antithrombotic effects; however, the hemorrhagic responses vary and are largely dependent on products. The release of TFPI following i.v. and s.c. administration in a primate model also demonstrated the product individuality and the relevance of this inhibitor to the actions of LMWHs. The effect of repeated administration mimicking the post-surgical prophylaxis of DVT also exhibited product based augmentation of the antithrombotic or hemorrhagic effects. Antithrombotic and hemorrhagic studies are reported that compare the pharmacologic profile of some of the available LMWHs. Product individuality in terms of relative potency in different assays and the failure of standardization protocols to provide any guidelines for product substitution and prediction of the clinical effects is also addressed.

Animals↗
PubMed1995

Anticoagulant and antithrombotic actions of a semisynthetic beta-1,3-glucan sulfate.

Sulfation of the natural polysaccharide curdlan results in anticoagulantly active beta-1,3-glucan sulfates whose activity depends on various structural parameters. In this study the anticoagulant and antithrombotic effects of one of these beta-1,3-glucan sulfates (GS) were compared with those of a porcine mucosal heparin. GS produced a concentration dependent anticoagulant effect in all the global coagulation assays with the exception of the anti-Xa assay. The best activity was found in the APTT and the thrombin time assays indicating that protease generation and the direct inhibition of thrombin may be sites of actions of this agent. Whereas the anticoagulant activity of GS was approximately 5 fold lower compared to heparin, a 32 fold higher concentration (ED50 = 550 micrograms/kg) was needed for an antithrombotic effect similar to heparin (ED50 = 17.2 micrograms/kg) in a rabbit model of stasis thrombosis. In contrast to this, when a rat model of clamping induced jugular vein occlusion was used to produce vascular obstruction, GS produced similar antithrombotic actions to heparin. At a 250 micrograms/kg dosage, both agents doubled the number of clampings required for complete vascular obstruction. Since the mechanical injury to the blood vessel is the primary determinant of the thrombogenic response, GS may inhibit some of the pathophysiologic mechanisms responsible for the occlusion of the blood vessel. The current study also points to the fact that the global anticoagulant effects may not reflect the antithrombotic potential of newer sulfated carbohydrate derived drugs.

Animals↗
PubMed1995

TFPI antigen levels in normal human volunteers after intravenous and subcutaneous administration of unfractionated heparin and a low molecular weight heparin.

Tissue factor pathway inhibitor (TFPI) is an important mediator of the in vivo anticoagulant/antithrombotic properties of unfractionated heparin (UFH) and low molecular weight heparin (LMWH). The vascular pool of TFPI is released into the circulation after intravenous and subcutaneous administration of both UFH and LMWH. We have administered LMWH (Ardeparin) and UFH to normal human volunteers in a dose dependent manner. Our results demonstrate that the TFPI antigen levels increase upon the intravenous and subcutaneous administration of UFH and Ardeparin. Because of the better bioavailability of LMWH by the subcutaneous route at equigravimetric dosages, Ardeparin released more TFPI than UFH. However, when given intravenously an identical release of TFPI from the vasculature has been observed. The plasma concentration of TFPI was increased 0.5-2 fold when UFH or Ardeparin was administered subcutaneously and was 3 fold higher when administered intravenously. This profound increase in TFPI antigen levels was dependent on the dosage of Ardeparin administered. This release in TFPI correlates with prolongation of the Heptest clotting assay. However, it appears from this study that TFPI release precedes the elevation of the Heptest clotting time.

Adult↗
PubMed1995

Molecular profiling and weight determination of heparins and depolymerized heparins.

The recently proposed calibrant LHN-1 (lot F537; henceforth designated F537), for the molecular weight (MW) determination by high-performance size-exclusion chromatography of heparins, is shown here to have a range too narrow to allow for the accurate MW determination of all low molecular weight heparins (LMWHs). We have recently demonstrated, by this same methodology, that a chemically degraded benzyl ester of unfractionated heparin, heparin mass calibrator (HMC), is a better calibrant. Weight-average MW, number-average MW, peak MW, and dispersity values were calculated with F537, HMC, and by a reference narrow-range-calibration method for various LMWHs and unfractionated heparins. Values for these parameters determined with HMC were not significantly different from those determined by the reference method until the MW of the substance exceeded 15.0 kDa. In contrast, the MW profile obtained with F537 was appreciably different from that obtained by the reference method for samples with MWs > 7.5 kDa. The range exhibited by HMC should allow this calibrant to be used for both LMWHs and unfractionated heparins.

Heparin↗
PubMed1995

A comparative study on the mechanism of the anticoagulant action of mollusc and mammalian heparins.

The anticlotting activities on some steps of the coagulation cascade of mollusc and mammalian heparins were studied. AT III-high affinity heparin is a more potent inhibitor than unfractionated heparin and mollusc heparin in the intrinsic and extrinsic pathways of thrombin and factor Xa generation. Mollusan heparin has about the same activity as the AT III high affinity-heparin on the inhibition of factor Xa and thrombin in the presence of antithrombin III and four times more inhibitory activity than unfractionated heparin on the heparin cofactor II mediated inhibition of thrombin.

Animals↗