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Biomedical subjects

K Andrassy

Publications and source records attributed to K Andrassy.

At least 55 records · Page 3Linked to original sources
PubMed1996

Are the pharmacokinetic parameters of low molecular weight heparins predictive of their clinical efficacy?

Low molecular weight heparins (LMWHs) are obtained by partial enzymatic or chemical depolymerisation and further chromatographic separation of standard unfractionated heparin. Most pharmacokinetic studies of LMWHs in humans have utilised the anticoagulant action against activated clotting factors. LMWH contains both high and low affinity fragments to antithrombin-III. Antithrombotic efficacy of LMWH is dependent on both fragments. LMWH levels peak 10 minutes after intravenous administration and are detectable for 5-8 hours. Following subcutaneous administration, maximum anti-factor Xa levels are demonstrable up to 12 hours or longer. Anti-factor IIa activity is eliminated faster than anti-factor Xa activity when measured with chromogenic substrates, but not with thrombin generation. The half-lives of the various LMWHs and their bioavailability, as measured by their anti-factor Xa or anti-factor IIa activities differ to a certain extent and clinical efficacy cannot be predicted from such data. On the basis of clinical studies, the antithrombotic potential of s.c. LMWHs for general surgery lies approximately around 2000 anti-factor Xa units and for high-risk patients around 4000 anti-factor Xa units, with no increased bleeding tendency. This is derived from investigations with enoxaparin, reviparin and dalteparin and is not valid for other LMWH derivatives.

Absorption↗
PubMed1996

Antibodies to neutrophil elastase: a study in patients with vasculitis.

Whether antibodies to elastase (EL) exist in autoimmune disease is controversial, due in part to inadequate methods used to determine antibody titers. We have developed a highly sensitive and specific enzyme-linked immunosorbent assay, using immobilized EL and mouse monoclonal antibodies for standardization. The specificity of the enzyme-linked immunosorbent assay was confirmed by absorption studies and Western blot analysis. Using this enzyme-linked immunosorbent assay, antibodies to EL were found in antineutrophil cytoplasmic antibody-positive vasculitis patients to a higher degree than reported in the literature (in eight of 108 patients with Wegener's granulomatosis and in 15 of 78 patients with microscopic polyangiitis). Patients with Wegener's granulomatosis or microscopic polyangiitis and antibodies to EL had significantly more severe renal involvement, as indicated by the higher frequency of dialysis dependency. Also in contrast to reported data, antibodies to EL were found less frequently in patients with systemic lupus erythematosus (nine of 64 patients). Binding of systemic lupus erythematosus sera to uncoated plates, giving a nonspecific reaction, was seen quite frequently, which might explain the discrepancy.

Adult↗
PubMed1996

Elevated levels of markers of endothelial cell damage and markers of activated coagulation in patients with systemic necrotizing vasculitis.

Activation of coagulation and endothelial cell damage was studied in 47 patients with small vessel vasculitis [Wegener's granulomatosis (WG) and microscopic polyangiitis (MP)] by measurement of thrombin-antithrombin III complexes (TAT), fibrin-D-dimers (D-dimers), von Willebrand-factor (vWF) concentration and plasma thrombomodulin (TM) levels. There was a close correlation between disease activity (DA) in patients with WG or MP and markers of endothelial cell damage (correlation TM/DA r = 0.46 for WG and r = 0.43 for MP) and activated coagulation (correlation TAT/DA r = 0.58 for WG and r = 0.55 for MP). Elevation of the markers of activated haemostasis and endothelial cell damage was reversed when remission was obtained by specific treatment. The markers studied were particularly helpful in cases where measurement of antineutrophil cytoplasmatic antibodies (ANCA) did fail to assess disease activity.

Adult↗
PubMed1995

[Systemic lupus erythematosus and silicosis].

A 60-year-old stonemason, suffering for many years from joint pains and exertional dyspnoea, developed a high fever with weight loss. Physical examination revealed reddening of light-exposed skin areas, fine rales and overly warm and reddened hand and knee joints. Abnormal laboratory findings were increased erythrocyte sedimentation rate of 66 mm/h, C-reactive protein concentration of 1 mg/dl, haemoglobin of 9.4 g/dl and white cell count of 3300/microliters. Urine contained albumin (100 mg/dl) and cylinders. Titres of both antinuclear and anti-ds-DNA antibodies were elevated (1:2560 and > 97 U/ml, respectively). The chest radiography showed enlarged hili, as well as reticular and nodular shadows which histologically showed silicosis. Systemic lupus erythematodes was diagnosed and the patient was treated with prednisone (2 mg/kg daily), the dosage being reduced to 12 mg daily within 3 months. When the joint pains recurred, azathioprine (50 mg daily) was added for 24 months. At present he is receiving prednisone (12 mg daily) and there has been no recurrence for 4 years.

Diagnosis, Differential↗
PubMed1995

Hemolytic uremic syndrome complicating postinfectious glomerulonephritis in the adult.

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura is known to occur as a secondary complication of primary renal diseases, specifically of lupus nephritis, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In a patient without a family history of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura we observed biopsy-confirmed postinfectious glomerulonephritis with humps, with simultaneous subendothelial hyaline deposits and fibrinoid thrombi in arterioles. The patient had a history of febrile pharyngitis with diarrhea 10 days prior to renal biopsy. He presented with transient elevation of serum creatinine, a nephritic sediment, and hypertension not exceeding 160/100 mm Hg. The patient also had purpura, transient thrombocytopenia, and signs of intravascular hemolysis. Results of verocytotoxin serology were negative. With the exception of isolated microhematuria, all findings reverted to normal within 8 weeks without any specific treatment. This case illustrates that hemolytic uremic syndrome/thrombotic thrombocytopenic purpura may complicate primary postinfectious glomerulonephritis in adults.

Adult↗
PubMed1995

PDGF and TGF-beta contribute to the natural course of human IgA glomerulonephritis.

PDGF and TGF-beta are known mediators of mesangial cell proliferation and matrix expansion. The presence of these regulatory factors was examined in 30 renal biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and protein level. Normal renal tissue served as control. The mRNA expression of PDGF A/B chains, PDGF-beta R and TGF-beta 1 was evaluated by means of RT/PCR with subsequent Southern blot hybridization and/or non-radioactive in situ hybridization. In addition, PDGF-AB/BB, PDGF-beta R, TGF-beta isoforms (beta 1, beta 1 + 2, beta 2 + 3), the small TGF-beta 1 latency associated peptide (TGF-beta 1 LAP) and the extracellular matrix proteins tenascin and decorin were analyzed by immunocytochemistry. The expression of growth factors was correlated with light microscopic and clinical features. Compared to normal control kidneys, an increased expression of PDGF-BB/PDGF-beta R mRNAs and the corresponding proteins was observed in all biopsies with IgA-GN. Up-regulation was related to the degree of glomerular proliferation and the extent of fibrosing interstitial lesions. In contrast, there was a discordance between TGF-beta 1 mRNA and protein expression (evaluated by immunocytochemistry). In all biopsies, irrespective of the stage of the disease, abundant TGF-beta 1 transcripts were detected, whereas TGF-beta 1 immunoreactivity was expressed to a lesser degree and disclosed a more variable staining pattern. In patients with significant proliferative glomerular lesions and minor tubulointerstitial alterations, TGF-beta 1 positivity was confined to areas of glomerular proliferation, whereas in cases with more severe histology including sclerosing lesions TGF-beta 1 immunoreactivity was less prominent. The distribution and the intensity of TGF-beta 1 LAP staining commonly exceeded the positivity noted for TGF-beta 1, indicating only limited TGF-beta 1 activation. A decreased reactivity for tenascin accompanied the morphological features of glomerular sclerosis. The staining patterns and the fact that only very few inflammatory cells, particularly CD68 positive monocytes/macrophages, were detected in glomeruli confirm that predominantly resident glomerular cells (mesangial and endothelial cells) are the major source of up-regulated growth factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the severity of proliferative glomerular changes, PDGF seems to represent a potential indicator of activity in this condition. It is suggested that an imbalance between PDGF and TGF-beta (by restricted translation and/or activation) production contribute to the progressive nature of IgA-GN.

Adult↗
PubMed1995

Compassionate treatment of Wegener's granulomatosis with rabbit anti-thymocyte globulin.

UNLABELLED: The purpose of this study was to evaluate the effect of treatment with anti-thymocyte globulin in patients with Wegener's granulomatosis, untreatable with cyclophosphamide and steroids. MATERIALS AND METHODS: Five patients with active Wegener's granulomatosis, either not responsive to standard therapy, or who could not tolerate alkylating agents received a single course of rabbit anti-thymocyte globulin (ATG). RESULTS: Four patients showed a favourable response to treatment with partial or complete remission of disease activity, during a follow-up period of five to twelve months. One patient had progressive retroorbital granuloma, which resulted in enucleation of the eye. Side effects of the ATG treatment were mild with chills and fever during the first infusion, and development of serum sickness in two patients. Two other patients had labial herpes simplex shortly after the start of treatment, no other infectious complications were seen. CONCLUSIONS: We conclude that ATG treatment seems to be an effective treatment for patients with severe Wegener's granulomatosis.

Adult↗
PubMed1995

[Panarteritis nodosa with kidney and spleen rupture: diagnostic and therapeutic possibilities].

Classic polyarteritis nodosa is a necrotizing vasculitis affecting medium- and small-sized arteries. Renal involvement from aneurysm formation is common and can result in perirenal or intrarenal bleeding. The gold standard of diagnostic procedures is the arteriography. Treatment of choice is a combination of steroids and cyclophosphamide, but in the case of severe hemorrhage surgery is mandatory. Patients with PAN need at least 2 years of long-term therapy; repeated arteriography will establish the efficacy of therapy.

Adult↗
PubMed1995

Expression of receptors for advanced glycosylated end-products in renal disease.

BACKGROUND: Advanced glycation endproducts (AGEs) are believed to mediate long-term complications in diabetes mellitus. In this context we studied the expression of the receptor for AGEs (RAGE) in the kidney of patients with a variety of different renal diseases. METHODS: RAGE was detected by immunocytochemistry in renal biopsies. We compared the staining for RAGE in nine patients with diabetic nephropathy, 20 with inflammatory and/or immune complex and 10 with non-inflammatory renal diseases. Normal renal tissue from seven patients with tumour nephrectomies served as controls. RESULTS: In controls the only cells expressing RAGE constitutively were interstitial cells and vascular smooth muscle cells (6/7), while distal tubular cells were rarely positive (1/7). Endothelial cells of arteries/arterioles, glomerular endothelial cells, podocytes, and capsular epithelial cells were consistently negative. In diabetic nephropathy, inflammatory and/or immune complex, and non-inflammatory renal diseases, all cell types mentioned above became positive for RAGE. Whilst the distribution of RAGE in the tissue was quite similar, staining intensity in inflammatory and/or immune complex diseases was higher than in diabetic nephropathy. CONCLUSION: RAGE induction in the kidney is not specific for diabetic nephropathy and occurs in other types of renal diseases as well.

Adolescent↗
PubMed1994

[Acute myoglobinuric kidney failure as a consequence of autoaggressive behavior in mental retardation].

A 49-year-old female with mental retardation was admitted with suspected renal insufficiency with a raised creatinine (5.1 mg/dl), hyperkalaemia (5.6 mmol/l), and a 12-hour history of diffuse abdominal pain and persistent vomiting. On admission, she had a haematoma around the right shoulder and arm-pit, swelling of the right upper-arm, and severe limitation of movement of the right hand. These injuries were the result of trauma some 5 days previously. She was a long-term inpatient in a psychiatric clinic, with a history of autoaggressive behaviour, which had led to several fractures in the past as a result of falls. The creatinine kinase was elevated to 6680 U/l. The suspected diagnosis of acute oliguric renal failure due to rhabdomyolysis was confirmed by the presence of marked myoglobinuria (409 ng/ml). Because of the delay in diagnosis, acute renal failure developed, and the patient required haemodialysis for 20 days. Because of their many predisposing factors, psychiatric patients represent a special risk group for development of rhabdomyolysis, recognition of which is often delayed.

Acute Kidney Injury↗
PubMed1994

Neutralization of the anticoagulant activity of low molecular weight heparin LU 47311 (Clivarin) in man by protamine chloride.

Bleeding induced by unfractionated heparin (UFH) can be antagonized by protamine as shown by normalization of thrombin time and aPTT. In order to learn about the neutralization capacity of protamine against the anticoagulant effects of LU 47311 a comparison study vs UFH was performed in 12 healthy male volunteers. Whereas the prolongation of aPTT and thrombin time induced by both heparins was reversed, inhibition of anti F Xa activity was not. A anti F Xa activity following injection of UFH was immediately antagonized by only 20-40% with LU 47311. A rebound phenomenon of LU 47311 after protamine chloride was not detected. The platelet system remained unchanged.

Adult↗
PubMed1994

Pharmacokinetics of Clivarin a new low molecular weight heparin in healthy volunteers.

The antithrombotic activity and pharmacokinetics of Clivarin, a low molecular weight heparin was randomly studied in 10 healthy male volunteers. Doses of 20, 40, 60 and 80 anti F Xa U/kg BW were injected intravenously and subcutaneously in crossover fashion. The heparin concentrations were measured by inhibition of clotting assays (anti IIa and anti Xa activities using amidolytic assays and [dilute] thrombin time). The pharmacokinetic profile of Clivarin is characterized by a linear relationship between dose and absorption, relatively low clearance and a long elimination half-life, and a high anti Xa/anti IIa ratio of 5.3.

Adult↗
PubMed1994

Nomenclature of systemic vasculitides. Proposal of an international consensus conference.

The following are some of the conclusions and proposals made at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. 1. Although not a prerequisite component of the definitions, patient age is recognized as a useful discriminator between Takayasu arteritis and giant cell (temporal) arteritis. 2. The name "polyarteritis nodosa," or alternatively, the name "classic polyarteritis nodosa," is restricted to disease in which there is arteritis in medium-sized and small arteries without involvement of smaller vessels. Therefore, patients with vasculitis affecting arterioles, venules, or capillaries, including glomerular capillaries (i.e., with glomerulonephritis), are excluded from this diagnostic category. 3. The name "Wegener's granulomatosis" is restricted to patients with granulomatous inflammation. Patients with exclusively nongranulomatous small vessel vasculitis involving the upper or lower respiratory tract (e.g., alveolar capillaritis) fall into the category of microscopic polyangiitis (microscopic polyarteritis). 4. The term "hypersensitivity vasculitis" is not used. Most patients who would have been given this diagnosis fall into the category of microscopic polyangiitis (microscopic polyarteritis) or cutaneous leukocytoclastic angiitis. 5. The name "microscopic polyangiitis," or alternatively, "microscopic polyarteritis," connotes pauci-immune (i.e., few or no immune deposits) necrotizing vasculitis affecting small vessels, with or without involvement of medium-sized arteries. Cryoglobulinemic vasculitis, Henoch-Schönlein purpura, and other forms of immune complex-mediated small vessel vasculitis must be ruled out to make this diagnosis. 6. The name "cutaneous leukocytoclastic angiitis" is restricted to vasculitis in the skin without involvement of vessels in any other organ. 7. Mucocutaneous lymph node syndrome must be present to make a diagnosis of Kawasaki disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

A role for histones and ubiquitin in lupus nephritis?

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.

Animals↗