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Biomedical subjects

U Hoffmann

Publications and source records attributed to U Hoffmann.

At least 73 records · Page 4Linked to original sources
PubMed1999

Generation of anti-hirudin antibodies in heparin-induced thrombocytopenic patients treated with r-hirudin.

BACKGROUND: Hirudin is a small protein with strong thrombin inhibition that may be antigenic. The generation and disappearance of anti-hirudin antibodies were investigated in patients with heparin-induced thrombocytopenia who were treated with recombinant hirudin (r-hirudin) for >/=5 days. METHODS AND RESULTS: The IgA, IgE, IgG, and IgM isotypes of anti-hirudin antibodies were determined by ELISA before and after the start of r-hirudin therapy. A total of 56% of patients (13 of 23) developed >/=1 antibody isotype during therapy. No IgE antibodies were generated. IgA, IgG, and IgM antibodies were detected in 30% (7 of 23), 52% (12 of 23), and 17% (4 of 23) of patients, respectively. Four patients generated only IgG, 2 patients developed either IgM or IgG and IgM, 5 patients IgG and IgA, and 2 patients IgG, IgM, and IgA antibodies. IgM antibodies disappeared within 8 days of the cessation of r-hirudin. IgA and IgG antibodies disappeared within 1 year in all but 1 patient. Binding of purified IgG to r-hirudin in IgG antibody-positive patients (n=7) was demonstrated by competitive ELISA for r-hirudin. Of the 7 IgG antibody samples, 1 each neutralized or enhanced the anticoagulant activity of r-hirudin. CONCLUSIONS: R-hirudin may be antigenic in patients with heparin-induced thrombocytopenia. More comprehensive investigations will be required to determine the biological relevance of this and to establish the antibody-generation pattern in other diseases.

Adult↗
PubMed1999

[Adult progeria (Werner's syndrome)].

HISTORY: A 48-year-old man was referred with progressive claudication and nocturnal pain at rest in the right foot. During the last few years exercise-induced pain, ulcerations and necroses had developed in both legs without any evidence of relevant macroangiopathies. The patient showed marked morphological changes. He had bilateral cataracts since aged 35 years. At 40 years he had undergone a transurethral resection of a bladder carcinoma. One of his brothers showed similar morphological changes, but they were absent in his parents and three siblings. INVESTIGATIONS: Radiology of the right foot revealed extensive para-osseous soft-tissue calcifications. Direct right femoral angiography demonstrated distal occlusions of the anterior and posterior tibial arteries as well as subtotal occlusion of the fibular artery. Routine laboratory tests were normal, as were all measured antibody titres. TREATMENT AND COURSE: The peripheral vascular disease, stage IV, of the right leg were presumably caused by adult progeria (Werner's syndrome). Percutaneous transluminal angioplasty (PTAP) of the distal fibular and, later, of the posterior tibial artery was performed, and prostacyclins, antibiotics and platelet-aggregation inhibitors were administered. Although the PTAP was technically successful, the state of the right foot remained critical, due to the existing microangiopathy and the impaired proliferation and healing capacity of the tissues as part of the adult progeria. CONCLUSIONS: The diagnosis of adult progeria is usually made because of the patients' characteristic morphology and typical concomitant diseases. The average age of patients at diagnosis is 37 years. The syndrome is caused by a helicase defect. This enzyme group unwinds double-helix RNA and DNA. Because the syndrome is rare and gene analysis is complex, it is unlikely that a commercial screening test will become available.

Angiography↗
PubMed1999

Determination of heparin-induced IgG antibody by fluorescence-linked immunofiltration assay (FLIFA).

A fluorescence-linked immunofiltration assay (FLIFA) was developed for the determination of heparin-induced IgG in heparin-induced thrombocytopenia (HIT) type II patients. Protein A was immobilized on a nitrocellulose membrane to bind heparin-induced IgG of HIT type II patients. Fluorescein-5-isothiocynate (FITC)-heparin was added to platelet factor 4 present in normal serum to form the neo-antigen which was captured by heparin-induced IgG. The heparin-induced IgG was quantified by the relative fluorescence intensity (RFI) of bound FITC-heparin. Values were expressed as a RFI ratio (RFI patient / RFI normal) and were 1.965+/-0.413 in HIT type II patients (n = 36) and 1.064+/-0.162 in healthy controls (n = 50, p<0.0001). The intra- and inter-assay coefficients of variation were 4.9 and 10.4%, respectively. The heparin-induced IgG FLIFA will be useful in individual and epidemiological studies in patients during treatment with heparin. The FLIFA technique offers an alternative, rapid and sensitive methodological approach for studies on the interaction between antigen-antibody or ligand-receptor.

Anticoagulants↗
PubMed1999

Assessment of hepatic perfusion in pigs by pharmacokinetic analysis of dynamic MR images.

The purpose of this study was to evaluate a new method based on magnetic resonance imaging for the characterization of hepatic perfusion. In nine pigs dynamic MRI was performed before and after partial occlusion of the portal vein. The pharmacokinetic analysis of the contrast enhancement resulted in a set of parameters (amplitude, A; perfusion rate, kp; elimination rate, kappa(e1); lag time, t(lag)) of which kp was expected to correlate with hepatic perfusion. Reference measurements were done with ultrasound flow-meters and with a thermal diffusion probe (TDP). MR perfusion rate kp significantly dropped under partial portal vein occlusion from an average of 11.3 to 4.9 min(-1) (P < 0.001), while the difference in amplitude A was not significant. The correlation between kp and the TDP measurement was r = 0.89 (P < 0.001). Pharmacokinetic analysis of MRI contrast enhancement provides a non-invasive assessment of hepatic perfusion.

Animals↗
PubMed1999

Multicompartment analysis of gadolinium chelate kinetics: blood-tissue exchange in mammary tumors as monitored by dynamic MR imaging.

The blood-tissue exchange kinetics of gadopentetate were studied in 49 malignant and benign mammary tumors. Signal enhancement was monitored simultaneously in the aorta and in tumor for 10.5 minutes after the beginning of a 1 minute i.v. infusion of the contrast medium (CM). Kinetic analysis was based on a model with two compartments for systemic pharmacokinetics and up to three kinetically distinct compartments for tumor. Kinetic heterogeneity, ie, two or more compartments with different exchange rate constants in a given tumor, was found in 85% of carcinomas, 38% of fibroadenomas, and 14% of mastopathic tumors. The within-tumor average of CM exchange rates was 1.22 (0.62-1.65) min(-1) in carcinomas, 0.38 (0.26-0.60) min(-1) in fibroadenomas, and 0.16 (0. 12-0.20) min(-1) in mastopathies (median and interquartile distances). The area under the signal enhancement-time curve of the aorta varied 4.5-fold between individuals. It is concluded that individual CM kinetics in arterial blood should be taken into account when CM exchange rates between blood and tumor are to be determined and that a kinetic model for potentially malignant tumors should allow for kinetic heterogeneity.

Adenocarcinoma↗
PubMed1999

[Staging of bronchial carcinoma].

Staging of any tumor, i.e. determination of the extent of the disease, serves to select the patients who might profit from curative surgical intervention or to define those patients with inoperable carcinomas who should be referred for other therapies, such as chemotherapy or irradiation. Furthermore, accurate staging is necessary for assessment of prognosis, for radiation therapy planning, and for differentiation of those with small-cell lung cancer or for follow-up examinations of small-cell lung cancer patients after during and after chemotherapy. The primary radiological staging and diagnostic modalities for assessment of bronchial carcinomas are computed tomography (CT) of the thorax including liver and adrenal glands, abdominal sonography, and bone scintigraphy. Magnetic resonance imaging (MRI) should be reserved for specific indications, e.g. infiltration of the chest wall or staging of patients with intolerance/allergy to intravenous contrast medium. The clinical value of nuclear medicine techniques, such as [18F]2-fluoride-2-desoxy-D-glucose positron emission tomography (FDG-PET) for evaluation of lymph nodes and distant metastases, In-111 octreotide/somatostatin receptor scans for staging of small-cell lung cancer, and thallium-201 SPECT are currently being assessed in numerous studies, although these techniques are already in routine use. In future these or nuclear medicine techniques, as well as techniques using molecular-based contrast material, especially for MR imaging, currently in experimental status, may yield serious potential for staging purposes.

Carcinoma, Bronchogenic↗
PubMed1999

Pulmonary magnetic resonance angiography.

In the past few years magnetic resonance angiography (MRA) of the pulmonary vasculature has advanced from a research tool to a clinically relevant imaging modality. Early 2D phase-contrast and time-of-flight (TOF) sequences without the use of contrast agents were time-consuming and limited by considerable imaging and motion artifacts. Since the introduction of MR scanners with stronger gradients (> 20 mT/m) and contrast-enhanced techniques, imaging of the pulmonary vasculature with adequate spatial resolution within a single breathhold is now possible. In the detection of pulmonary embolism in the lobar or segmental arteries, contrast-enhanced MRA is now on the verge of being considered an established modality, possibly competing with conventional pulmonary angiography and contrast-enhanced helical CT. In the future, utilization of phased-array torso coils, the application of navigator pulse sequences, and 3D time-resolved ultrafast MRA will overcome the final limitations of current techniques. Blood-pool MR contrast agents may provide a "one-stop-shopping" approach to the investigation of lower extremity veins and pulmonary arteries in venous thromboembolism.

Contrast Media↗
PubMed1999

Effects of hyperoxia on oxygen uptake kinetics in cystic fibrosis patients as determined by pseudo-random binary sequence exercise.

Patients with cystic fibrosis (CF) have been shown to exhibit impaired oxygen uptake (VO2) kinetics independent of their physical fitness. This study investigated whether oxygen supplementation improves VO2 kinetics in CF as determined by cycle ergometry at submaximal exercise intensities using a pseudo-random binary sequence exercise test i.e. a simultaneous application of different frequencies of sinusoidal work. The subjects were 9 CF patients and 13 healthy controls (HC) and they exercised while breathing humidified and heated air with a fractional concentration of oxygen in inspired air (F(I)O2) of either 0.21 or 0.40. With a F(I)O2 of 0.21 the respiratory exchange ratio (R) was higher in CF than in HC both at rest (0.91 vs 0.81) and during exercise (0.97 vs 0.89). Oxygen saturation (SO2) was slightly lower in CF. but remained above 90% during exercise (92.7% vs 95.2%). Spectrum analysis revealed that in CF, the amplitude ratio (AR) between V02 and exercise intensity was lower over a wide frequency range (P < 0.05). In addition, CF showed a larger negative phase shift (PS) at lower frequencies (P < 0.005). With a F(I)O2 of 0.40, SO2 increased to about 97% in both groups; while R remained higher in CF (0.92) compared to HC (0.81). In the control group, the O2 supplement raised AR but the VO, kinetics of the CF patients were not significantly affected. In HC the enhanced AR during oxygen supplementation would suggest a cardiopulmonary limitation of VO2 at the onset of submaximal exercise. In CF patients low AR and PS would indicate an attenuated VO2 response attributable to an impaired oxygen utilization in the muscles because the oxygen supplement normalised SO2 but failed to improve R and VO2 kinetics.

Adolescent↗
PubMed1999

Spontaneous reversibility of early reobstruction following percutaneous transluminal angioplasty.

Early reocclusion and late restenosis are well-known problems after percutaneous transluminal angioplasty (PTA). We report here on a phenomenon not described so far in two patients with peripheral arterial occlusive disease who had PTA of the common iliac and the superficial femoral artery, respectively. Both had a good hemodynamic and clinical initial result. However, within two days after PTA symptomatic reobstruction occurred documented by noninvasive measurements. Noteworthy, this reobstruction was spontaneously reversible within days. The possible pathomechanism is discussed.

Angiography↗
PubMed1999

Dose-dependent increase of transcapillary diffusion of sodium fluorescein after histamine microinjections.

BACKGROUND: To study the dose-dependent effects of histamine on capillary permeability in human skin, using the microinjection technique. PATIENTS AND METHODS: Eight healthy volunteers (2 w, 6 m; mean age 33 years) were included in the study. On two separate occasions, glass microcannulas with a tip diameter of 7 to 9 microns were inserted into the subepidermal layer of the skin at the distal medial tibia surface of each lower limb with a micromanipulator. In each subject, 0.5 microliter of 3 different concentrations of histamine solution (0.1/1000, 0.01/1000 and 0.001/1000) were injected and compared to the solvent (0.9% NaCl). Transcapillary diffusion of intravenously administered Na-fluorescein was assessed simultaneously using two fluorescence videomicroscopy systems. Off-line video densitometry was performed in an area of 0.56 mm2 around the injection sites and fluorescence light intensities were measured in arbitrary units (AU) at 10, 30, 60, 120 and 600 s after dye appearance. RESULTS: Compared to the solvent histamine microinjections resulted in a dose-dependent increase of mean fluorescence light intensities (FLI). Whereas mean FLI for the 0.001/1000 histamine injection was only significantly elevated 10 min after dye appearance (p < 0.05) an increase of mean FLI was already observed 10 s after dye appearance following the 0.1/1000 histamine injection (p < 0.05), which was more pronounced at later time points (p < 0.001). Mean FLI's for the 0.01/1000 histamine solution were in between and resulted in significantly elevated values 1 min to 10 min after dye appearance (p < 0.05). CONCLUSIONS: We conclude that the microinjection technique together with fluorescence videomicroscopy described previously [6] is able to document a dose-dependent effect of histamine microinjections on skin capillary permeability. The technique may facilitate to determine appropriate dosages not only of histamine in order to test the effect of antagonists on human skin capillary permeability.

Adult↗
PubMed1999

Association of heparin-induced skin lesions, intracutaneous tests, and heparin-induced IgG.

BACKGROUND: Cutaneous heparin-induced allergic reactions to subcutaneous heparin may begin 2-5 days after administration. The relation of the delayed-type hypersensitivity and a systemic immunologic response is controversial. The present investigation aimed to analyze the occurrence of thromboembolic complication, pathologic heparin-induced platelet activation (HIPA), and the presence of circulating heparin-induced IgG in patients with heparin-induced skin reactions. METHODS: Intracutaneous tests, HIPA assay, and heparin-heparin IgG antibodies were performed in nine patients with heparin-induced skin lesions. RESULTS: Six of eight patients showed positive intracutaneous tests to heparin and to four low-molecular-weight heparins. Three of six heparin-positive patients presented hypersensitivity to a heparinoid, too. Two of three patients had a positive HIPA test and elevated heparin-induced IgG antibodies. Both patients developed complications presenting as heparin-induced skin necrosis or arterial thrombosis. Two of nine patients were treated with danaparoid, 4/9 patients received r-hirudin, and 1/9 received oral coumarin. In 2/9 patients, anticoagulant therapy was stopped, but these patients will receive r-hirudin if indicated. CONCLUSIONS: On the basis of the coincidence of local and systemic hyperreactivity to heparin and danaparoid, patients with heparin-induced skin lesions should receive r-hirudin, a nonheparin compound, for anticoagulant treatment.

Adult↗
PubMed1999

Periarteritis nodosa presenting as a breast lesion: report of a case and review of the literature.

We describe a 34-year-old woman with periarteritis nodosa (PAN) presenting as a breast lesion. Localized involvement of the breast is an unusual manifestation of PAN. To date, 10 cases have been reported: all were in women with an age range of 45-78 years (mean 63). In most cases, breast lesions were an isolated finding, and the prognosis was favourable, setting them apart from the more common form of systemic PAN. The case presented is unusual in that vasculitis developed in the postpartum period, and was associated with cutaneous PAN-like lesions elsewhere on the body, and digital artery occlusion. The most important differential diagnoses of PAN of the breast are infectious mastitis, mammary malignancy and other forms of idiopathic vasculitides of the breast, e.g. giant cell arteritis and Wegener granulomatosis.

Adult↗
PubMed1999

Immunologic response to recombinant hirudin in HIT type II patients during long-term treatment.

We prospectively investigated 27 patients with heparin-induced thrombocytopenia (HIT) type II who were subsequently treated with r-hirudin. Patients with venous or arterial thromboembolism were treated with activated partial thromboplastin time (aPTT)-controlled intravenous r-hirudin (n = 19; mean 19.3 d) followed by subcutaneous r-hirudin (n = 6; mean 22.5 d) and oral anticoagulation. Patients without thromboembolism were treated with subcutaneous r-hirudin (n = 8; mean 25.9 d). Four patients were readmitted to subcutaneous r-hirudin for a mean duration of 32 d. The incidence of r-hirudin antibodies was 84% for intravenously treated patients and 50% in subcutaneously treated patients. The patients (n = 27) showed a 74% overall incidence of r-hirudin antibodies, mainly of the IgG-subclass, without seroconversion before day 6 and after day 32 of r-hirudin treatment or during r-hirudin treatment. None of the patients showed onset or recurrence of venous or arterial thromboembolism, systemic allergic reactions or IgE-antibody development. During intravenous and subcutaneous administration of r-hirudin the aPTT and the ecarin clotting time was increased in the antibody-positive patients compared to antibody-negative patients. Therefore we assume that r-hirudin antibodies may reduce r-hirudin metabolism.

Adult↗
PubMed1999

Physiological reflux and venous diameter change in the proximal lower limb veins during a standardised Valsalva manoeuvre.

OBJECTIVES: the aim of this study was to provide normal values for venous diameter at rest, and venous diameter and physiologic venous reflux during a standardised Valsalva manoeuvre. The impact of the patient's sex, body mass index (BMI), and family history was investigated. MATERIAL AND METHODS: eighty legs of 40 healthy volunteers were investigated in a supine position. The median age was 28 years (range 20-66 years). The common femoral vein (CFV), the proximal superficial femoral vein (SFV) and the proximal long saphenous vein (LSV) were investigated by duplex sonography. The following parameters were assessed: resting diameter (VDrest) and maximum diameter (VDmax) as well as reflux time (tr) during the Valsalva manoeuvre. The Valsalva manoeuvre was elicited by a forceful expiration into a tube system. The standard values used were a pressure of 30 mmHg, established within 0.5 seconds (s) and maintained over a time period of at least 3 s. RESULTS: mean VDrest and VDmax were 8.3+/-2.2 and 11.1+/-2.8 mm in the CFV, 5.9+/-1. 3 and 7.2+/-1.6 mm in the SFV and 3.5+/-0.9 and 4.3+/-1.4 mm in the LSV. Mean values for tr were 0.61+/-0.63 s in the CFV, 0.25+/-0.26 s in the SFV and 0.28+/-0.40 s in the LSV. A BMI >22.5 kg/m2 was associated with statistically significant larger values for VDrest and tr. If adjusted for BMI, tr in the SFV and the LSV did not differ by sex. For healthy subjects with first-degree relatives suffering from varicose veins (n=19), mean VDrest in the SFV as well as VD in the LSV was significantly larger (p=0.02, 0.05, respectively). Coefficients of variation for repeated measurements (VDrest, VDmax, tr) in the same segment varied between 3.3% and 16. 4% for the three investigated sites. CONCLUSIONS: normal values for VDrest and VDmax as well as reflux time during a standardised Valsalva manouevre were assessed in the proximal lower limb veins. The influences of BMI, sex and family history were investigated. The described standardised Valsalva manoeuvre led to highly reproducible results and can be recommended for further research projects or as a routine procedure for the assessment of venous reflux.

Adult↗
PubMed1999

Long-term results after recanalisation of chronic iliac artery occlusions by combined catheter therapy without stent placement.

OBJECTIVES: to evaluate the long-term outcome after recanalisation of chronic iliac artery occlusions by combined catheter therapy without stent placement. DESIGN: retrospective study. MATERIAL AND METHODS: between 1979 and 1995 75 consecutive patients were treated (53 men, 22 women; mean age 63.1+/-13.7 years; mean length of the occluded segment 6.9+/-3.5 cm). The indication for treatment was incapacitating claudication (n=55) or chronic critical ischaemia (n=20). At follow-up clinical data, pulse volume and pressure measurements were recorded and duplex-sonography and/or angiography performed, if clinically indicated. RESULTS: mean follow-up was 7. 2+/-4.1 years. The primary clinical success rate was 64% at 12 months, 57% at 4 years and remained stable for up to ten years. The secondary clinical success rate after 12 months was 83% and remained stable at 81% for up to 10 years. Peripheral embolisation as complication of the intervention occurred in 18 patients (24%) and was treated by percutaneous thromboembolectomy in 15 patients during the same procedure. In the remaining three patients no intervention was necessary. One patient had to undergo surgery for a groin haematoma. CONCLUSIONS: recanalisation of segmental chronic iliac artery occlusions by catheter therapy without stent placement has favourable long-term results comparable to primary stent placement. Randomised controlled studies are required to determine the appropriate role of catheter therapy alone and primary or selective stenting for iliac artery occlusions.

Angiography↗
PubMed1999

Lymphatic microangiopathy of the skin in systemic sclerosis.

METHODS: The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. RESULTS: At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. CONCLUSION: Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

Adult↗