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Biomedical subjects

U Hoffmann

Publications and source records attributed to U Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed2001

Laboratory diagnosis of heparin-induced thrombocytopenia type II after clearance of platelet factor 4/heparin complex.

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is limited by assay sensitivity. We investigated whether laboratory confirmation can be improved after antigen clearance by determining free antibody and combining the results of antigenic and biologic assays. Blood samples were collected over 5 to 6 weeks in 14 HIT patients. As an antigenic assay, the fluorescence-linked immunofiltration assay (FLIFA) was performed, and as a biologic assay, the carbon 14-labeled serotonin release assay was performed. At day 1 when heparin was stopped, 11 of 14 patients showed positive results in both assays; thus each assay had a sensitivity of 80%. The 3 patients with negative results seroconverted in one or both assays during the subsequent 7 days. Combining the positive results of the assays increased the sensitivity to 100% at day 7, regardless of whether the antigenic or the biologic assay was performed first. Both assays became negative in all patients within 5 to 6 weeks. The sensitivity of antigen and biologic assays in HIT patients increased to 100% after the time course of the heparin-induced antibody. We assume that in some HIT patients the free antibody can be detected after withdrawal of heparin and after clearance of the platelet-factor 4/heparin complex.

Aged↗
PubMed2001

Adult moyamoya disease with peripheral artery involvement.

We report the case of a young white woman in whom cerebrovascular moyamoya disease, which was associated with nonarteriosclerotic peripheral artery disease of the subclavian, iliac, and femoropopliteal arteries, was diagnosed by means of angiography. During 8 years of follow-up, the peripheral artery disease progressed, without any signs characteristic of systemic inflammation or vasculitis, leading to severe calf and arm claudication. Despite the absence of histologic confirmation, this observation strongly suggests that peripheral artery involvement may be a feature of moyamoya disease. To our knowledge, this is the first report of an association of classical cerebrovascular moyamoya disease with peripheral artery disease.

Adult↗
PubMed2001

Cutaneous reactions to anticoagulants. Recognition and management.

Anticoagulant-induced skin reactions appear as allergic or necrotic responses to vitamin K antagonists or heparins. Cutaneous allergy has been reported with danaparoid sodium and flush reactions have been seen with hirudins. The pathogenesis of the reactions differs between drugs. Generally, they occur between days 3 to 10 after the start of treatment, but may also occur later. In patients experiencing necrosis with a vitamin K antagonist, concomitant protein C deficiency, protein S deficiency or lupus anticoagulant has been described, whereas the precise mechanism of the other reactions is unknown. In patients with allergic reactions to heparins, cutaneous tests may help to identify alternative anticoagulants. Such a test cannot be performed in patients with skin necrosis. In patients with heparin-induced skin reactions danaparoid sodium may be used after negative intracutaneous testing in some patients and a hirudin may be used without testing in all patients. Heparin-induced skin necrosis has been reported to be mediated by immunologic mechanisms and to be associated with a high frequency of heparin-induced thrombocytopenia type II. Surgical excision of the necrosis may be required. If further anticoagulation is indicated in any patient, extreme caution has to be taken when restarting oral anticoagulants. Because a large number of anticoagulants available today, safe treatment of all patients experiencing anticoagulant-induced skin reactions is feasible.

Anticoagulants↗
PubMed2001

Improved laboratory confirmation of heparin-induced thrombocytopenia type II. Time course of antibodies and combination of antigen and biologic assays.

We studied whether laboratory confirmation of heparin-induced thrombocytopenia (HIT) can be improved after antigen clearance by determining free antibody and combining the results of an antigenic and a biologic assay. Blood samples taken over 40 days in 14 patients with HIT with thromboembolism underwent fluorescence-linked immunofiltration and the carbon 14-serotonin release assays. Of the 14 patients, 11 showed positive results in both assays at day 1 after stopping heparin. The 3 patients with negative results seroconverted in one or both assays during the subsequent 7 days. Combining the positive results of the assays increased the sensitivity from 85% at day 1 to 100% at day 7. Assay results became negative in all patients within 40 days. The platelet count normalized between days 2 and 9 after withdrawal of heparin. It is assumed that the free antibody can be detected after withdrawal of heparin and after clearance of the platelet factor 4-heparin complex in patients with HIT.

Aged↗
PubMed2001

Long-term results of percutaneous thrombo-embolectomy in patients with infrainguinal embolic occlusions.

BACKGROUND: The aim of the study was to review early and long term clinical results of percutaneous thrombo-embolectomy in patients with acute embolic occlusions of the infrainguinal arteries. METHODS: Retrospective analysis of consecutive cases. A total of 88 procedures in 84 patients were performed between 1986 and 1996 in a University Hospital (46 men, 42 women; mean age 67.6 +/- 14.4 years). Patients with a history of chronic symptomatic arterial occlusive disease were not included in the analysis. Indications for treatment were severe claudication (n = 45 procedures) and limb threatening ischaemia (n = 43 procedures). Percutaneous thrombo-embolectomy was performed via an ipsilateral approach by means of an end hole aspiration catheter. Local thrombolysis or balloon angioplasty was used as appropriate during the intervention. Follow-up included clinical data, ankle pressure measurements, pulse volume recordings and duplex sonography or angiography if indicated. RESULTS: Technical success was achieved in 85 (96.6%) of the 88 procedures. Two patients (2.3%) suffered major and two patients (2.3%) minor complications. One patient died within 30 days after the procedure. Mean follow-up was 3.7 +/- 2.9 years. Twelve patients (16%) were lost to follow-up. Primary clinical success rate was 88.4% at one and 81.7% at two years and declined to 76.5% at eight years. Out of the 16 interval failures 10 (63%) were due to recurrent embolism to the same leg. They resulted in nine catheter reinterventions and one bypass graft. Six patients were treated conservatively. Cumulative mortality was 11.7% at one year and increased to 29.5% at eight years. CONCLUSIONS: From our single centre experience we conclude that catheter treatment of acute embolic occlusion of infrainguinal arteries is safe and has favourable long-term RESULTS. We therefore regard the technique as a less invasive alternative to surgery.

Aged↗
PubMed2001

Oestrogen concentrations in the faeces of bitches.

Few data are available concerning excretion of oestrogen from bitches. During anoestrus, oestrogen concentrations are low in the blood of bitches and, therefore, a sensitive method for measuring concentrations of these hormones by analysis of faeces was developed. Daily faecal samples from bitches (n = 25) of various breeds were analysed (collected for 20 days after the start of pro-oestrous vulvar sanguinous discharge), as well as single samples from bitches in anoestrus (n = 30; samples from 16 of these bitches were also analysed during pro-oestrus and oestrus) and ovariohysterectomized bitches (n = 18). Samples (0.5 g mixed with 0.5 ml water) were extracted and after the samples were cleaned the unconjugated oestrogen content was measured, using a group specific enzyme immunoassay. Oestrone and oestradiol were identified as the predominant immunoreactive oestrogens by HPLC. In samples collected on the first day of pro-oestrous vulvar sanguinous discharge, oestrogen content was 9.3-231.1 nmol kg-1 faeces (median 45.5 nmol oestrogen kg-1 faeces). On day 8 of discharge, oestrogen content was 21.8-539.5 nmol kg-1 faeces (median 114.1 nmol oestrogen kg-1 faeces). Oestrogen content in bitches in anoestrus was 2.2-65.2 nmol kg-1 faeces (median 18.5 nmol oestrogen kg-1 faeces), whereas ovariohysterectomized bitches excreted lower amounts of oestrogens (range 0.7-18.1 nmol kg-1; median 4.4 nmol kg-1). The differences between oestrogen content in ovariohysterectomized bitches and bitches during anoestrus and oestrus were significant (P < 0.001). It is concluded that the method developed in the present study is suitable for monitoring the low production of oestrogens during anoestrus.

Anestrus↗
PubMed2000

A new therapeutic option by subcutaneous recombinant hirudin in patients with heparin-induced thrombocytopenia type II: a pilot study.

We prospectively studied 15 patients suffering from acute heparin-induced thrombocytopenia (HIT) type II with and without thromboembolic events and 4 patients with anamnestically known HIT type II recurrently requiring thromboprophylaxis in order to develop new therapeutic strategies by subcutaneous recombinant hirudin administration. Patients with acute venous or arterial thromboembolism were treated with aPTT-controlled intravenous (mean: 19.3 days) followed by subcutaneous r-hirudin (mean: 22.5 days). Patients without thromboembolism were treated with subcutaneous r-hirudin (mean: 25.9 days). Four patients were readmitted to subcutaneous r-hirudin (mean: 32 days). When r-hirudin was administered subcutaneously following intravenous treatment, mean baseline (prior to the injection) and mean peak (1.5-2.5 hours after the injection) aPTT ratios were 1.1 (+/-0.2) to 1.7 (+/-0.48) and 2. 48 (+/-0.43) to 2.52 (+/-0.4) times normal value, respectively. Mean baseline and mean peak ECT ratios were 1.2 (+/-0.12) to 1.9 (+/-0. 22) and 2.2 (+/-0.25) to 2.6 (+/-0.11) times the upper normal value, respectively. When r-hirudin was initially administered subcutaneously, mean baseline and mean peak aPTT ratios were 1.41 (+/-0.25) to 1.61 (+/-00.28) and 1.88 (+/-0.26) to 2.06 (+/-0.09) times the normal value, respectively. Mean baseline and mean peak ECT ratios were 1.25 (+/-0.2) to 1.5 (+/-0.38) and 2.01 (+/-0.21) to 2.23 (+/-0.25) times the upper limit of normal, respectively. Patients who received recurrent subcutaneous r-hirudin had mean baseline and peak aPTT values of 1.5 (+/-0.35) to 1.75 (+/-0.156) and 2.0 (+/-0.33) to 2.1 (+/-0.18) times the normal value, respectively. Mean baseline and peak ECT ratios were 1.3 (+/-0.26) to 1.65 (+/-0.09) and 1.94 (+/-0.256) to 2.7 (+/-0.23) times the upper limit of normal, respectively. The overall cumulative incidence of r-hirudin antibodies was 12/19 (63%) with a significant accumulation of r-hirudin in antibody-positive patients compared to antibody-negative patients (p<0.05). No patient suffered a new thromboembolic or major bleeding event. Subcutaneous administration of recombinant hirudin provides a long-term thromboprophylaxis regimen in HIT type II patients after passivation of acute thromboembolism.

Adult↗
PubMed2000

[Prevention of thrombosis with subcutaneous recombinant hirudin in heparin-induced thrombocytopenia type II. A pilot study].

BACKGROUND: Heparin-induced thrombocytopenia (HIT) type II is a severe complication of heparin therapy with a high incidence of thromboembolic events. AIM: The aim of this prospective study was to evaluate efficacy and safety of prophylaxis of thromboembolism with subcutaneous r-hirudin (25 mg twice daily) in patients with HIT type II. PATIENTS AND METHODS: From 01/06/1997 until 01/08/1999, 19 patients were prospectively included into the study. During subcutaneous r-hirudin application (25 mg twice daily) the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT) were measured twice daily prior to and 2 hours after the morning injection. RESULTS: Ten patients (mean age: 68 years; two men, eight women) with thromboembolic events were intravenously treated with r-hirudin (mean 19.3 days) with a target aPTT of 1.5 to 2.5 times normal values followed by subcutaneous r-hirudin (mean 22.5 days). Five Patients without thromboembolism immediately received subcutaneous r-hirudin (mean 25.9 days; mean age: 61 jahre; two men, three women) after cessation of heparin. Four patients requiring prophylaxis of thromboembolism received subcutaneous r-hirudin (mean 32 days; mean age: 68 years; four women) because of HIT type II in the past. Mean aPTT-values prior to and 1.5-2.5 hours after the morning injection were 1.2 to 1.7 and 2.0 to 2.3 times normal values, respectively. The ECT was prolonged by 1.2 to 1.7 and 2.3 to 2.5 times the upper normal value, respectively. Thromboembolic or bleeding events were not observed during the study. CONCLUSION: The subcutaneous application of r-hirudin provides an alternative for primary and secondary prophylaxis of thromboembolism in HIT type II patients.

Aged↗
PubMed2000

Urinary apo(a) excretion is not altered by changes in glomerular filtration rate and renal plasma flow in healthy males.

Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic disease. However, information concerning the site of Lp(a) catabolism and breakdown is scarce. Several studies have shown that, in renal insufficiency, plasma Lp(a) levels are elevated, and that after normalisation of kidney function they return to normal. We have recently shown that fragments of apo(a) are found in the urine of healthy individuals. Despite this evidence that apo (a) is excreted into the urine, the mode of excretion of apo(a) remains unclear. Since it has been reported that intravenous infusion of somatostatin can reduce glomerular filtration rate (GFR) and renal plasma flow (RPF), we analysed urinary apo(a) excretion in ten healthy volunteers receiving somatostatin infusions. The infusion of somatostatin led to reversible changes in GFR and RPF. Apo(a) excretion was constant in all 10 individuals over the entire time course when normalised for creatinine. There was a highly significant correlation between plasma Lp(a) levels and urinary apo(a) values. Changes in renal plasma flow and glomerular filtration rate did not alter urinary apo(a) excretion. We conclude that a constant amount of apo(a) is excreted into urine, depending on plasma Lp(a) levels, and that urinary apo(a) excretion is not altered by changes in GFR and RPF in healthy males.

Adult↗
PubMed2000

Radiological signs of a left atrial aneurysm.

We report a case of an acquired mid-sized extrapericardial aneurysm in the area of the left atrial appendage and demonstrate the diagnostic impact of several imaging methods. Chest radiography gave a hint to the diagnosis with a bulky mass of soft tissue density appearing adjacent to the left atrial appendage. Transthoracic as well as transesophageal echocardiography missed the origin of the aneurysm. Magnetic resonance imaging helped to establish the diagnosis with use of a coronal imaging plane. No contrast agent was necessary. Thus, the combination of chest X-ray and MRI provided excellent support for patient management.

Aged↗
PubMed2000

A major susceptibility locus for atopic dermatitis maps to chromosome 3q21.

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies. Along with asthma and allergic rhinitis, atopic dermatitis is an important manifestation of atopy that is characterized by the formation of allergy antibodies (IgE) to environmental allergens. In the developed countries, the prevalence of atopic dermatitis is approximately 15%, with a steady increase over the past decades. Genetic and environmental factors interact to determine disease susceptibility and expression, and twin studies indicate that the genetic contribution is substantial. To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria. A genome-wide linkage study revealed highly significant evidence for linkage on chromosome 3q21 (Zall=4.31, P= 8.42 10(-6)). Moreover, this locus provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71,alpha=44%), further supporting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic dermatitis and that the study of this disease opens new avenues to dissect the genetics of atopy.

Adolescent↗
PubMed2000

Treatment of an acute flush reaction caused by subcutaneous r-hirudin with pegylated hirudin.

We report a patient who was treated with recombinant (r)-hirudin for heparin-induced thrombocytopenia and developed a flush reaction twice upon re-exposure to 25 mg of subcutaneous r-hirudin. Antihirudin IgG antibodies developed. The patient received 50 mg of PEG-hirudin subcutaneously over 2 days. No side-effects occurred. The level of IgG antihirudin antibodies increased. Ecarin clotting time and thrombin inhibition S2238 assay were not influenced by the patient's IgG antihirudin antibody. PEG-hirudin may be used in patients with intolerance to r-hirudin because of a dissociation of the allergenic and immunogenic properties of the pegylated drug.

Acute Disease↗
PubMed2000

Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia.

[14C]-Serotonin release assay (14C-SRA) from platelets is considered to be the most sensitive test for laboratory confirmation of heparin-induced thrombocytopenia (HIT). This study compared 14C-SRA with an enzyme immunoassay (EIA) to determine the release of serotonin from platelets in the presence of heparin and serum from HIT patients. The normal range (median, 2.5 and 97.5 percentiles) of serotonin release from platelets in healthy subjects (n = 149) is 38 ng/ml (19 and 62) measured by EIA-SRA. Serum from HIT patients (n = 42) released 2548 ng/ml (244 and 7987) serotonin in the presence of 0.1 IU/ml heparin and 29 ng/ml (13 and 76) in the presence of 100 IU/ml heparin. One hundred per cent and 15% of HIT samples exhibited an elevated serotonin release from platelets in the presence of 0.1 IU/ml low molecular weight (LMW) heparin, 2100 ng/ml (869 and 5968), or danaparoid, 272 ng/ml (143 and 403), respectively. The sensitivity and specificity of the EIA-SRA was 100% and 97.4% and of the 14C-SRA 100% and 92.9% in HIT patients. No false-positive results were found in patients receiving heparin (n = 28), in patients with elevated levels of bilirubin (n = 5), in patients with antiphospholipid antibody syndrome (n = 10) or in non-HIT patients (n = 78) with both assays. The EIA technique to quantify serotonin release from platelets provides a reliable non-radioactive method to diagnose heparin-induced thrombocytopenia and to assess in vitro crossreactivity of low molecular weight heparins and heparinoid.

Anticoagulants↗
PubMed2000

Re-exposure to recombinant (r)-hirudin in antihirudin antibody-positive patients with a history of heparin-induced thrombocytopenia.

Patients with a history of heparin-induced thrombocytopenia (HIT) and antibodies to hirudin were re-exposed to recombinant (r)-hirudin for prophylaxis of thromboembolism. Four patients were re-exposed to 2 x 25 mg of subcutaneous r-hirudin for 8-27 d. Two patients were re-exposed once, one patient twice and one four times. Re-exposure was well tolerated in all patients and no thromboembolism occurred. Antihirudin IgG (4/4 patients), IgA and IgM (1/4 patients) antibody levels increased. Baseline ecarin clotting times showed high variability. Patients with antibodies to hirudin may be re-exposed but anticoagulant monitoring is mandatory.

Adult↗
PubMed2000

Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin.

Heparin-induced thrombocytopenia type II is a serious, immune-mediated complication of heparin therapy. Due to its low cross-reactivity with heparin-associated antibodies (10-20%), danaparoid has successfully been administered in these patients. In recent studies, r-hirudin as a potent and specific thrombin inhibitor, was demonstrated to be a safe and effective anticoagulant. We report a pregnant woman with systemic lupus erythematosus and recurrent venous thromboembolism who suffered from heparin-induced thrombocytopenia type II while treated with dalteparin sodium. Positive cross-reactivities with danaparoid were found. Anticoagulation with 15 mg subcutaneous r-hirudin was performed twice daily from the 25th week of pregnancy until delivery. No thromboembolism or bleeding or fetal toxicity of r-hirudin was detected. Recombinant hirudin is a potent and specific thrombin inhibitor that can be used as a safe and effective anticoagulant in pregnancy.

Adult↗