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Biomedical subjects

K Jäger

Publications and source records attributed to K Jäger.

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

Recombinant hirudin as an anticoagulant during cardiac operations: experiments in a pig model.

OBJECTIVE: The efficacy and safety of recombinant hirudin (r-hirudin) compared with heparin as an anticoagulant during open-heart surgery has been studied in a pig model. METHODS: A total of 18 Göttingen minipigs were randomly divided into three treatment groups and subjected to cardiopulmonary bypass for 1 h. Heparin-treated animals received a bolus of unfractionated heparin of 400 IU/kg body weight. Recombinant hirudin was given by a bolus injection of 1 mg/kg body weight, followed by a 1 h lasting infusion of 1 mg/kg body weight per h. The heparin-anticoagulated animals and one group of the hirudin-treated animals additionally received aprotinin at a dosage of 17500 KIU/kg body weight (KIU, kallikrein inhibitory units). In the second group of r-hirudin-treated animals, the aprotinin was replaced by saline. RESULTS: The extracorporeal circuit remained patent for a 1 h pump period in all of the animals studied. There was no evidence of vascular occlusion or clot formation in the r-hirudin-treated animals. The anticoagulant efficacy of the hirudin protocol used is further demonstrated by the results of electron-microscopical scans of the pump-line filters. Fibrin deposits were visible only in the heparin-treated animals and not in r-hirudin-treated pigs. Despite this strong anticoagulant effect, there was no evidence of an increased bleeding tendency in r-hirudin-treated pigs. Moreover, histological studies showed a statistically significant (P < 0.05) higher incidence of tissue bleeding in the heparin/aprotinin-treated animals compared with the r-hirudin/aprotinin-treated pigs. Studying the platelet function, a statistically significant (P < 0.01) better preserved ADP- and collagen-induced platelet aggregation was seen in the r-hirudin/aprotinin-treated animals when compared with heparin/aprotinin-treated animals. CONCLUSIONS: These data demonstrate that r-hirudin can be used successfully as an alternative anticoagulant to heparin during cardiac operations including cardiopulmonary bypass. The better preservation of platelet function suggests that r-hirudin may reduce the postoperative risk of bleeding.

Animals↗
PubMed1997

Quantitative monitoring of blood supply to knee joint transplants in dogs.

BACKGROUND: Transplantation of vascularized knee joints has become technically feasible, but graft rejection as well as failures of the vascular anastomoses remain critical hazards. We therefore tested the potential of repetitive non-invasive duplex sonography to detect changes of the arterial blood flow following canine knee joint transplantation. METHODS: Four transplantations and, as controls, 4 replantations of intact canine knee joints were performed. The follow-up was 6 months. During this period, repetitive duplex sonography measurements as well as tests of knee joint function were performed. Six months postoperatively, angiographies were performed and all joints were explanted for histological investigation. RESULTS: The luminal diameters of the implanted popliteal artery remained constant in the transplanted animals (preop. 2.6 +/- 0.2 mm, 6 months postop. 2.7 +/- 0.2 mm) but decreased in the autografted controls (preop. 2.9 +/- 0.3 mm, postop. 2.0 +/- 0.3 mm). The time-averaged velocity of the popliteal artery blood flow decreased in both groups 1 month postoperatively. Subsequently, blood flow velocity recovered in transplanted animals but remained low in replanted controls. Significant arterial wall thickening was also detected in transplanted animals as compared to controls. Six months postoperatively, hypervascularization of transplanted joints was confirmed by angiography and thickening of the arterial wall by histology. Furthermore, histology identified mild to chronic allograft rejection in all transplanted joints in spite of controlled cyclosporin A trough level immunosuppression. CONCLUSIONS: Chronic rejection of transplanted vascularized knee joints appears to be associated with vessel wall thickening and hypervascularization rather than with vascular rarefaction (picture of the 'arbre mort') that is characteristic of the rejection of most parenchymatous organs. Duplex sonography appears to be sensitive in detecting the corresponding changes of blood supply.

Angiography↗
PubMed1997

Role of hemostatic risk factors for restenosis in peripheral arterial occlusive disease after transluminal angioplasty.

In a prospective study, the role of various hemostatic factors known to be associated with thrombotic risk was investigated in 71 patients with peripheral arterial occlusive disease (PAOD, stages II through IV, Fontaine; aged 68 +/- 13 years). Laboratory investigations were done before; 1, 24, and 48 hours after; and 3 and 6 months after percutaneous transluminal angioplasty (PTA). Thirty of 71 (42.3%) patients developed restenosis (> 50% reduction of the lumen diameter) at the site of PTA within 6 months, verified by color-coded duplex sonography. Significantly increased levels of thrombin-antithrombin III complexes (P < .01), prothrombin fragments 1 + 2 (P < .01), and D-dimers (P < .01) were found 1 hour, as well as 24 to 48 hours, after PTA. Fibrinogen (P < .01) and von Willebrand factor (P < .01) were significantly higher 48 hours after PTA. Restenotic patients as a whole had higher plasma fibrinogen (3.46 +/- 1.12 versus 2.95 +/- 0.62 g/L, P < .01) and C-reactive protein (25.4 +/- 46.7 versus 7.9 +/- 6.9 mg/L, P < .05) at baseline, as well as higher fibrinogen (P < .05) and prothrombin fragments 1 + 2 (P < .01) during months 3 to 6 after PTA. There was a nonsignificant tendency for higher values of von Willebrand factor (206 +/- 98% versus 184 +/- 100%, P = .2) at baseline in patients with restenosis, whereas tissue plasminogen activator, plasminogen activator inhibitor, coagulation screening tests, blood cell counts, and serum lipids showed no significant difference between the two groups. The relative risk for developing restenosis within 6 months while having high fibrinogen (> 2.8 g/L) or C-reactive protein at baseline was 2.80 (95% CI: 1.30-6.02, P < .01) and 1.96 (95% CI: 1.07-3.58, P < .05), respectively. Patients with critical limb ischemia (stage III/IV, Fontaine) had significantly higher fibrinogen and von Willebrand factor at repeated points of time, as well as significantly higher C-reactive protein and lower creatinine clearance at entry. In the logistic regression risk factor analysis, baseline plasma fibrinogen, C-reactive protein concentration, and the severity of the arterial disease were significantly predictive of restenosis. Our results indicate that high procoagulant factors and persistent thrombin generation of the hemostatic system might promote restenosis, particularly in patients with extended atherosclerosis. This finding suggests that new treatment strategies should be taken under consideration for patients with PAOD and PTA.

Angioplasty, Balloon↗
PubMed1997

Anticardiolipin antibodies are not associated with restenosis or endothelial activation after percutaneous transluminal angioplasty.

OBJECTIVE: Restenosis following percutaneous transluminal angioplasty (PTA) continues to be a major clinical problem. Anticardiolipin antibodies (aCL) have been established as risk factors for venous or arterial thrombosis. The aim of this study was to assess: a) the influence of positive aCL upon restenosis within 6 months after PTA, b) the possibility of a seroconversion from negative to positive aCL after PTA and c) a possible link between positive aCL and endothelial activation. EXPERIMENTAL DESIGN: 71 patients (50 men and 21 women, age 68+/-13 years) with peripheral arterial occlusive disease (PAOD, Fontaine II-IV) undergoing a successful PTA entered the study and were prospectively followed for 3 and 6 months thereafter. INTERVENTIONS: PTA was carried out successfully and noninvasive grading was done with duplex scanning. Laboratory investigation included aCL, thrombin generation markers, such as thrombin-antithrombin III complexes and prothrombin fragments 1+2, as well as thrombomodulin, soluble P-selectin, E-selectin and the vascular cell adhesion molecule-1, as endothelial activation markers. RESULTS: 30/71 (42.3%) patients developed restenosis (>50% reduction of the lumen diameter) within 6 months after PTA. 9/71(12.7%), had positive aCL IgG (19-35 GPL) and/or IgM (14-103 MPL) at all three measurements. 2/9 (22.2%) of aCL positive and 28/62 (45.2%) of aCL negative patients had restenosis at 6 months after PTA (relative risk RR=0.51, 95%-Cl: 0.14-1.78, chi2 non-significant). All other parameters did not differ between aCL positive and -negative groups. CONCLUSIONS: Our findings suggest that: a) patients with PAOD have a slightly higher prevalence of positive aCL compared to the general population, but no association is evident between positive aCL and restenosis within 6 months after PTA, b) no seroconversion from negative to positive aCL occurred within 6 months after PTA, c) no association of aCL with endothelial activation markers or thrombin generation markers was found.

Aged↗
PubMed1996

The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas: absence of t(2;5) in Hodgkin-analogous cell lines.

The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity thought to be related to Hodgkin'S disease (HD), but displaying also its own unique features. Cytogenetic studies of ALCL have demonstrated the presence of a (2;5)(p23;q35) translocation in a substantial number of these cases. Recently, the t(2;5) has been cloned and described to represent fusion of the NPM gene with the ALK gene on chromosome 5. To better define the spectrum of lymphomas containing this abnormality we have analyzed 50 continuous human cell lines established from various types of non-Hodgkin's lymphoma, ALCL and HD. In a first step, the expression of the NPM-ALK fusion gene was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). In a second step, the t(2;5)-carrying cells were tested for the translation of functional chimeric mRNA into a fusion protein by immuno-staining of single cells with a polyclonal antibody. The NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL cell lines. We were unable to find PCR evidence for the t(2;5) in any of the non-ALCL cell lines including other CD30+ cell lines. As all seven bona fide HD cell lines were NPM-ALK-negative, these results do not support the notion that the t(2;5) represents a chromosomal aberration common to both ALCL and HD.

Anaplastic Lymphoma Kinase↗
PubMed1996

Preservation of functional and regulatory domains of expressed bcl-2 genes in non-Hodgkin's lymphoma.

The most common translocation in human lymphoma, t(14;18)(q32;q21), recombines the bcl-2 gene with the immunoglobulin (Ig) heavy-chain locus leading to the production of high levels of chimeric RNAs and the resulting 26 kDa bcl-2 protein. The oncogenic role of the bcl-2 gene has been shown by the suppression of a variety of programmed cell deaths (apoptosis). Bcl-2 is able to interact with other members of the bcl-2 family through at least one of its conserved dimerization domains. Although overproduction of the wild-type protein appears sufficient for conferring a selective growth or a survival advantage to hematopoietic cells, the mode of activation of the proto-oncogene remains to be elucidated. In a first step, we examined and quantitated the expression of the bcl-2 gene in primary biopsies of non-Hodgkin's lymphomas (NHL) as well as in cell lines derived from NHLs. The results show that bcl-2 expression is found in a variety of hematopoietic lineages, but is most strongly associated with the B cell lineage. Within the B cell lineage, the expression levels vary depending on the differentiation as well as on the t(14;18) rearranged status. The quantitative measurements show high steady-state mRNA levels in early and in t(14;18) arranged B cells, whereas bcl-2 expression decreases with further B cell maturation and differentiation. In a second step we analyzed the bcl-2 mRNA for secondary genetic alterations, which may alter regulatory regions rendering it more tumorigenic. For this purpose, we chose a combined RT-PCR/SSCP method in order to screen out mutations of alleles which are not expressed. Different migration patterns of SSCP products were found only in two cell lines and subsequent sequencing revealed that the functional domains are not affected. Our data suggest that the dimerization properties of this protein are preserved in tumor cells and that modifications of the bcl-2 gene by the somatic hypermutation mechanism are not involved and do not influence the pathobiology of NHL.

Base Sequence↗
PubMed1995

[Multiple familial glomangiomas].

Multiple glomus tumours represent a special variant of glomangiomatosis. Based on our observation, the clinical features, diagnosis and differential diagnosis are presented and possible therapeutic approaches are discussed.

Diagnosis, Differential↗
PubMed1995

The value of different resistance parameters in distinguishing biopsy-proved dysfunction of renal allografts.

The data concerning the value of duplex sonography in diagnosing parenchymatous renal allograft dysfunction are controversial. Most early studies did not take into consideration the many factors influencing resistance parameters. We therefore performed a prospective, biopsy-controlled study with exclusion of all known sources of error regarding resistance parameters. Furthermore we investigated the value of a new resistance parameter, the systolic deceleration percentage. Forty-seven duplex sonographic studies were performed on 43 patients (30 male, 13 female, median age 47 years, range 7-70). Fourteen studies were done on normally functioning grafts (control group) an average of 33 days after transplantation. Thirty-three studies were performed on dysfunctional grafts immediately prior to biopsy. Grafts which had been transplanted more than a year previously or with vascular findings or any other clinical or sonographic pathology probably explaining function deterioration were excluded. In all patients, the resistive index (RI), pulsatility index (PI) and systolic deceleration percentage (DP) were calculated in the main renal artery and in the interlobar artery. Of the 33 grafts with dysfunction, nine had vascular rejection (VR), 11 interstitial rejection (IR), 11 cyclosporin A toxicity (CAT) and two other histologies (OR). The mean RI in normal grafts (NO) was 0.71 +/- 0.06 in the main artery and 0.68 +/- 0.06 in the interlobar artery, in VR 0.86 +/- 0.12 and 0.80 +/- 0.18, in IR 0.72 +/- 0.05 and 0.70 +/- 0.07, in CAT 0.67 +/- 0.06 and 0.65 +/- 0.07 and in OR 0.64 +/- 0.07 and 0.60 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Bone marrow pathology in relapsing polychondritis: high frequency of myelodysplastic syndromes.

Haemopathologic changes were studied in 19 patients (13 male, six female, age 33-85 years, mean 56 years) with relapsing polychondritis (RP). Anaemia was found in eight, thrombocytopenia in two and splenomegaly in three patients. A total of 17 bone marrow biopsies were obtained from seven individuals. Bone marrow evaluation revealed myelodysplastic syndromes (MDS) with marked trilineage hyperplasia and dysplasia in three cases. Since an excess of myeloblasts or an increase of CD34 positive progenitor cells was not seen, the disorders were designated as 'refractory anaemia' or with regard to the dysplastic megakaryopoiesis 'MDS, unclassifiable'. Two of the three patients died after 10 and 55 months of follow-up due to infectious complications. In a further patient, bone marrow analysis repeatedly showed an unexplained granulopoietic hyperplasia, which, however, was not dysplastic enough to allow a diagnosis of MDS. The remaining patients had clearly reactive changes. Our findings support the notion that RP is a heterogenous disorder and suggest that RP may at times represent a paraneoplastic phenomenon of an underlying MDS. Since HLA typing revealed a significantly increased frequency of the antigen DR4 (10/17 patients positive = 59%), we hypothesize that immunological imbalances due to the MDS in conjunction with a specific immunogenetic background may play key roles in the pathogenesis of RP in these patients.

Adult↗
PubMed1994

[Current trends in the treatment of deep venous thrombosis].

The therapeutic procedure in established deep venous thrombosis (DVT) is summarized. Proximal (2 to 4 levels), symptomatic, recent DVT of less than three weeks duration is still treated in the clinic. The patient receives heparin intravenously, 5000 IU as initial bolus and subsequently 25,000-30,000 IU (approximately 400 IU per kilo bodyweight)/24 hours as continuous infusion or, in particular cases, 15,000 to 20,000 IU subcutaneously two times in 24 hours). Oral anticoagulation is started on the 1st day. Mobilisation takes place when symptoms regress, usually after 2-3 days. If further studies with low molecular weight heparins (LMH) confirm the good efficacy and tolerance, these compounds could replace heparin-schemes by a single daily subcutaneous injection. Also admitted to the hospital institution are patients with DVT and suspicion of pulmonary embolism and patients in whom fibrinolysis or thrombectomy are considered. The less expensive induction of anticoagulation on an outpatient basis and the subsequent follow-up treatment is in our opinion justified in patients with distal DVT (1-2 levels), older proximal DVT (and superficial venous thrombosis reaching the deep vein) and in patients with a thrombosed subclavian vein.) These patients are mobilized immediately under 12,500 to 15,000 IU heparin b.i.d. administered subcutaneously or alternatively injection of LMH's s.c. once per day (200 anti Xa-units/kg), changing over rapidly to p.o. vitamin K antagonists. For ambulatory patients LMH's may replace heparin for a single daily application if further studies confirm efficacy, this for mostly practical reasons. Long term anticoagulation by LMH could be ideal as for instance in pregnant patients.

Anticoagulants↗
PubMed1994

[Normal kidney function of the transplanted kidney in ipsilateral pelvic artery occlusion 15 years after transplantation. A case report].

A case of a 61-year-old women 15 years after right-sided renal transplantation is discussed. She suffered from rest pain in her right leg. Examinations revealed an occlusion of the right common iliac artery without signs of renal dysfunction or severe hypertension. After performing a extraanatomic femoro-femoral crossover bypass the patient had improved leg perfusion without a change in renal function.

Angiography↗
PubMed1994

[Mandibular hybrid dentures with 4 implants. An in-vitro stress analysis].

Four two-component implants (Bonefit) inserted in a mandibular model were fitted with various overdentures and then subjected to tension analysis using wire strain gauges. The implants were positioned between the mandibular foramina of the model; data were obtained for mesial, distal, lingual and buccal compressive and tensile loads of 50 N on duplicates of the prosthodontic base at the level of the first molar, using a measuring wire gauge. The greatest forces were registered for the secondary-splint telescope crown prosthesis; these forces were up to three times as high as the corresponding axial load. In the case of bar attachments, it is not so much the strain on the implant when the prosthesis is loaded that tends to cause problems, but rather the original process of screwing down the overdenture on insertion. During this process, the implants are subjected to forces so high that the use of a torque indicator is deemed to be indispensable as a clinical consequence of this finding. For similar considerations, a conditionally removable bar construction should not be removed during follow-up examinations. Magnetically retained dentures, by contrast, barely exert any tensile forces on the implants.

Calibration↗
PubMed1994

[The incidence of post-thrombotic syndrome].

To evaluate the clinical and socio-economic importance of the postthrombotic syndrome (PTS), the following epidemiologic parameters are to be known: The incidence of deep vein thrombosis (DVT) in the population, the incidence of PTS after DVT, the prevalence of the PTS, the socio-medical consequences and the mortality. The DVT-incidence in the literature is about 3/1000 per year in the adult population. In our own follow-up study we found a global PTS-incidence of 40% (10% with, 30% without ulcer) 13 years after DVT. The PTS-incidence was correlated with the initial DTV-extent. The risk of PTS after 3- and 4-level DVT is significantly reduced by a successful fibrinolysis in the acute stage (p = 0.01). The mortality of patients with PTS is 3 times higher than in the population. 4% of the patients with PTS get disabled. To our knowledge an adequate study with direct assessment of the PTS-prevalence does not exist, but the PTS-prevalence can be deduced from large epidemiologic studies, such as the Basel-Study, in which the global chronic venous insufficiency is assessed. It amounts in the adult population between 0.5 to 1% for the PTS with and 3 to 5% for the PTS without ulcer.

Adult↗
PubMed1994

[Late sequelae of deep venous thrombosis: a 13-year follow-up of 223 patients].

To investigate late sequelae of deep vein thrombosis, 223 consecutive patients, 148 men, 75 women, aged 61.5 +/- 14.7 years, with phlebographically documented unilateral deep vein thrombosis were reexamined 13 years after the acute event. 29 had an isolated calf vein thrombosis, 45 a 2-level- (calf an popliteal), 72 a 3-level- (calf, popliteal and femoral), 62 a 4-level- (calf, popliteal, femoral and pelvic) thrombosis and 15 had a special location, for example an isolated popliteal or pelvic involvement. In the acute stage all patients were given full dose heparin followed by a six month period of oral anticoagulation. 144 were initially treated by thrombolytic treatment with streptokinase. Control phlebography 5-14 days after the onset of the treatment revealed no clearance in a so called negative group of 123 patients, aged 63.5 +/- 14.9 years, namely the 79 "only" anticoagulated and 44 unsuccessfully thrombolysed. In this negative group natural course of deep vein thrombosis can be studied. The positive group, comprising 100 patients, aged 59.4 +/- 13.9 years (25 with complete and 75 with partial lysis, after streptokinase), is compared with the negative group. The global incidence of postthrombotic syndrome in the natural course, 13 years after deep vein thrombosis, was 39%, 9.8% with and 29.2% without ulcer. Slight changes were noted in 25% and no change in 36%. The incidence of postthrombotic syndrome was correlated with the extent of the original thrombosis: 3.7% after isolated calf vein thrombosis vs. 55.2% after 4-level thrombosis. Moreover, the mortality after deep vein thrombosis and the frequency of recurrence in the interval and of venous symptoms were also correlated to the extent of the thrombosis. The incidence of post phlebitic syndrome in the positive group is significantly lower in patients with 3- and 4-level thrombosis (p = 0.01). Patients with complete and partial lysis also have less venous symptoms (for 3- and 4-level thrombosis p < 0.0001). Thus, the successful thrombolysis seems to be beneficial in long terms for patients with extended thrombosis. Therefore, in our hospital thrombolytic treatment is offered as an additional treatment to anticoagulation to patients with recent, less than 7 days old, 3- and 4-level-thrombosis without contraindications.

Adult↗
PubMed1993

The Pearson product-moment correlation coefficient is better suited for identification of DNA fingerprint profiles than band matching algorithms.

A database of DNA fingerprint profiles from permanently established human and animal cell lines was prepared with a computer program originally designed for numerical taxonomy of bacteria. Identifications of cell line DNA profiles were performed, both by the Pearson product-moment correlation coefficient and by band matching. Under the conditions used the Pearson product-moment correlation coefficient was consistently more reliable.

Algorithms↗