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D Janssen

Publications and source records attributed to D Janssen.

At least 19 recordsLinked to original sources
PubMed2006

Multipotent cells of monocytic origin improve damaged heart function.

Recently, we generated cells with multipotent properties from blood monocytes that in vitro differentiate into various somatic cell types. This experimental study investigated whether these programmable cells of monocytic origin (PCMO) succeed to restore left ventricular function after myocardial infarction (MI). PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left coronary artery. PCMO of male Lewis donors were injected either intramyocardially (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic assessment after 60 days demonstrated significant improvement of left ventricular function following i.my. transplantation of PCMO as well as early (24 h post-infarction) i.v. application while nonmodulated monocytes failed to restore heart function. The Y-chromosome-specific SRY gene of male donor PCMO was detected exclusively in infarcted hearts of animals, which demonstrated improved cardiac function. Subdivision of infarcted hearts by microdissection localized the SRY gene-containing department to the left ventricle adjacent to the infarcted area whereas the right ventricle remained negative. Successful generation of PCMO in access numbers allows their autologous use as a new additive treatment for early restoration of cardiac function after MI.

Animals↗
PubMed2006

Finite element analysis of the long-term fixation strength of cemented ceramic cups.

Clinical studies have shown that adequate fixation of ceramic cups using bone cement is difficult to achieve. As the cement-ceramic bond strength is low, a satisfactory fixation strength requires a cup design that allows mechanical interlocking, although such a design will probably promote cement cracking and therefore cup loosening in the long term. An investigation has been carried out to establish whether a cemented ceramic cup can be designed in such a way that both a satisfactory initial fixation strength is obtained and cement cracking is reduced to levels found around PE cups functioning well in vivo. By means of finite element analysis, the fatigue loading of three geometrically different cemented acetabular cups, with ceramic and PE material properties, has been simulated, and the severity of the crack patterns produced in the cement has been analysed. Furthermore, the fixation strength has been analysed by simulating a pull-out test prior to and after fatigue testing. All ceramic cups produced much larger amounts of cement damage during fatigue testing than any PE cup, caused by stress concentrations in the cement that were attributable to the high stiffness of the ceramic. Even a completely smooth ceramic cup produced more damage than a sharp-grooved PE cup. Owing to the excessive cement cracking, the fixation strength of the ceramic cups dropped after fatigue loading. It is concluded that cemented ceramic cups have an increased risk of long-term mechanical failure by comparison with PE cups, and that a ceramic cup design that combines sufficient fixation strength with low cement failure may be difficult to achieve.

Acetabulum↗
PubMed2005

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma.

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.

Biopsy↗
PubMed2005

Absence of a coding region for the helper component-proteinase in the genome of cucumber vein yellowing virus, a whitefly-transmitted member of the Potyviridae.

The complete nucleotide sequence of isolates of Cucumber vein yellowing virus (CVYV) has been determined. The viral genome comprises 9734 nucleotides, excluding a 3'-terminal poly(A) sequence. The genome of CVYV has a 5'-non coding and a 3' non coding region of respectively 67 and 240 nucleotides. The RNA of CVYV encodes a single polyprotein of 3148 amino acid residues and has a deduced genome organization and motifs typical for a member of the family Potyviridae. However, CVYV is atypical because it lacks a coding sequence region for the putative helper-component as well as conserved helper-component-proteinase motifs which may account for its vector relations. All the present coding regions were compared to those from several members of the Potyviridae family. CVYV is most closely related to Sweetpotato mild mottle virus confirming its assignation to the genus Ipomovirus, despite similarities with tritimoviruses.

Animals↗
PubMed2005

Why would cement porosity reduction be clinically irrelevant, while experimental data show the contrary.

Laboratory bench tests have shown that porosity reduction increases the fatigue life of bone cement specimens. Clinically, however, the effect porosity reduction is subject to debate. We hypothesized that the discrepancy between clinical and experimental findings is related to differences in the stress distribution, which is typically uniform in experimental test specimens, while stress concentrations exist in cement around hip implants. We simulated fatigue failure of cement in a finite element model of an experimental test specimen and of a transverse slice of a total hip arthroplasty with a sharp-cornered stem. Four levels of porosity were introduced. In the fatigue test specimen model, the fatigue life clearly was dependent on the level of porosity, while in the transverse slice model, the level of porosity had virtually no effect on failure of the cement mantle. The results of the simulations confirmed our hypothesis. In simulations of laboratory tests, pores clearly acted as crack initiators, while in the simulation of a real total hip reconstruction, crack formation was governed by local stress singularities. This explains why the beneficial effect of cement porosity reduction on the lifetime of total hip reconstructions may be hard to detect clinically.

Arthroplasty, Replacement, Hip↗
PubMed2005

[Thrombosis prophylaxis with heparins in intensive care patients].

Venous thromboembolism is a common complication in critically ill patients, resulting in high morbidity and mortality. Most patients treated in intensive care units (ICU) face a high risk of thromboembolic complications. There is a need for well-defined strategies for prevention of thrombosis in ICU patients. Mechanical methods such as compression stockings are frequently used, even though evidence for these measures in ICU patients is limited. Unfractionated heparin (UFH) is still the leading drug for thromboprophylaxis in ICU patients, but pharmacokinetic disadvantages such as low predictability of effect on anticoagulation are relevant, especially in ICU patients. Additionally, there is no sufficient evidence from clinical trials to support subcutaneous or intravenous prophylaxis with UFH. At least equivalent efficacy and safety of subcutaneous low molecular weight heparin (LMWH) compared with subcutaneous UFH have been shown in numerous studies investigating non-ICU high-risk groups. First studies on the use of LMWH in critically ill patients are promising. Some conclusions for safe use of subcutaneous LMWH in ICU patients can be drawn. Intravenous LMWH may be the optimal prophylaxis in most ICU patients, but there is a lack of sufficient data on dosing. Precautions such as monitoring of anticoagulation in patients with renal insufficiency are fundamental if LMWH is given. Further investigations into prevention of venous thromboembolism in ICU patients are urgently needed.

APACHE↗
PubMed2005

Finite-element analysis of failure of the Capital Hip designs.

The Capital Hip implant was a Charnley-based system which included a flanged and a roundback stem, both of which were available in stainless steel and titanium. The system was withdrawn from the market because of its inferior performance. However, all four of the designs did not produce poor rates of survival. Using a simulated-based, finite-element analysis, we have analysed the Capital Hip system. Our aim was to investigate whether our simulation was able to detect differences which could account for the varying survival between the Capital Hip designs, thereby further validating the simulation. We created finite-element models of reconstructions with the flanged and roundback Capital Hips. A loading history was applied representing normal walking and stair-climbing, while we monitored the formation of fatigue cracks in the cement. Corresponding to the clinical findings, our simulation was able to detect the negative effects of the titanium material and the flanged design in the Capital Hip system. Although improvements could be made by including the effect of the roughness of the surface of the stem, our study increased the value of the model as a predictive tool for determining failure of an implant.

Arthroplasty, Replacement, Hip↗
PubMed2004

Anticoagulation with low-molecular-weight heparin in patients with heart diseases.

Low-molecular-weight heparins (LMWH) were investigated in different cardiac diseases requiring anticoagulation. In case of short term usage advantages over intravenous unfractionated heparin (UFH) are of relevance, such as simple subcutaneous application, possibility for outpatient treatment and predictable effect on anticoagulation enabling abstention of laboratory monitoring in most cases. Thromboprophylaxis in acute medically ill patients and therapy of non-ST-elevation acute coronary syndromes (NSTE-ACS) are important indications, in which significant advantages for special LMWH as compared to Placebo or UFH were shown. A significant effect versus Placebo was demonstrated for the LMWH Dalteparin in prolonged anticoagulation until revascularisation procedure in NSTE-ACS. Promising results from trials were also published concerning use of LMWH Dalteparin and Enoxaparin in TEE-guided cardioversion. Findings from cohort trials are available for temporary or long term switch from oral anticoagulation to LMWH. Due to limited data, determination of individual benefit-to-risk ratio is of special importance to select suitable anticoagulation regimen in this case. Further investigations as a basis of general recommendations on standard dosing regimen are outstanding for use of each LMWH in percutaneous coronary interventions, as combination with Glycoprotein IIb/IIIa-inhibitors, in acute myocardial infarction and in artificial heart valves. In cardiology, most studies were performed with Dalteparin and Enoxaparin, suggesting these to be used in established cardiac indications as well as in further investigations.

Anticoagulants↗
PubMed2004

Phenotypical variation in cousins with the identical partial trisomy 9 (pter-q22.2) and 7 (q35-qter) at 16 and 23 weeks gestation.

From the study of numerical and structural chromosomal abnormalities, there is convincing evidence and accumulating information of a direct karyotype to phenotype correlation. Knowledge of phenotypic consequences of a specific chromosomal imbalance is important for genetic counseling and prenatal diagnosis. However, for unbalanced non-Robertsonian translocations a precise karyotype to phenotype correlation is difficult to predict for several reasons: (I) unbalanced non-Robertsonian translocations are rare, (II) the published case reports are often not age-matched, (III) varying breakpoints result in different lengths of the monosomic and trisomic segments and therefore the phenotype will depend on additional genes present or the loss of coding regions, and (IV) the combination of the same trisomy with different monosomies, or vice versa, can result in diverging phenotypes. Therefore, the study of the karyotype to phenotype correlation in affected relatives of the same age and the identical unbalanced translocation provides a good model to investigate phenotypic consequences of a specific genetic imbalance. We report of two second trimester fetuses with the identical major partial trisomy 9 (9pter-9q22.2) and minor partial trisomy 7 (q35-qter) resulting from a familial translocation (7;9)(q35;q22.2)mat. One fetus presented with a Dandy-Walker malformation, polymicrogyria, and mild dysmorphic features, whereas the other fetus showed unilateral cleft lip and palate without cerebral anomalies. Potential mechanisms for this different phenotypic expression of the same unbalanced translocation resulting in partial trisomy 9 and 7 in the two cousins and possible consequences for genetic counseling and prenatal diagnosis are discussed.

Abnormalities, Multiple↗
PubMed2004

Prophylaxis of port system-associated thromboses in advanced oncology patients using heparin flushing.

PURPOSE: Thromboses occur in connection with the use of venous port systems. Valid data on the instillation of heparin-based solutions in the lumen of the port system are lacking. METHODS: One hundred and seventy-three patients with malignancy from 19 centres who had participated in an observation study of subcutaneous thromboprophylaxis with dalteparin-Na (Fragmin P/-Forte) were analysed with a view to flushing the port systems and investigating any related influence on the occurrence of catheter-associated thromboses. RESULTS: All catheter-associated thromboses were seen in centres which used either no UFH, or UFH concentrations of up to 250 IU/ml (8/108; 7.4%). The rate of thrombosis rose to 10% (6/60) if no high-risk dose of dalteparin was applied subcutaneously. On the other hand, the rate of catheter-associated thromboses under the high-risk dose of dalteparin and/or a more highly concentrated instillation fluid, at 0.9% (1/113), was much lower. One haemorrhage from gastric ulcer occurred under the highest UFH concentration in the instillation fluid (2,500 IU UFH/ml). CONCLUSION: The results indicate that a concentration between 500 IU UFH/ml and 1,000 IU UFH/ml in the instillation solution, at the same time as high-risk prophylaxis with subcutaneous dalteparin for prevention of catheter-associated thromboses, is effective in patients with manifest tumour disease. The instillation of LMWH-based solutions at a concentration of approx 500 anti-Xa units/ml should be discussed as a pending issue.

Adult↗
PubMed2004

Topoisomerase IIalpha expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome.

Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3-4 years. Treatment usually consists of combination chemotherapy, often including topoisomerase (topo) inhibitors such as doxorubicin, etoposide and mitoxantrone. Topo IIalpha is an enzyme that is needed whenever uncoiling of DNA is necessary during the cell cycle. The enzyme is a marker of cell proliferation. We analyzed the expression of topo IIalpha in relation to Ki-67 and the clinical outcome in patients with MCL. Biopsy specimens from 95 untreated patients enrolled in two multicenter trials (1975-1985) were investigated immunohistochemically with monoclonal antibodies against topo IIalpha (Ki-S4) and Ki-67 (Ki-S5). Patients with low (0-10%) topo IIalpha expression had a median overall survival time of 49.0 months, compared to 17.0 months for patients with high (more than 10%) topo IIalpha expression. The Kaplan-Meier analysis showed a significant difference in the overall survival time related to the percentage of topo IIalpha (P<0.001) and Ki-67 (P<0.001) positive tumor cells. Multivariate Cox regression analysis revealed the expression of topo IIalpha as the most important prognostic factor (P<0.001) in MCL superior to the international prognostic index (IPI), the Ki-67 index and other clinical characteristics.

Antigens, Neoplasm↗
PubMed2004

Molecular signals for late Tertiary/early Quaternary range splits of an Eurasian steppe plant: Clausia aprica (Brassicaceae).

Several vegetation belts stretch continuously from Europe to Asia, taiga and steppe being most prominent. Numerous plant species within these belts share a conspicuous distribution area, which is longitudinally contracted or disrupted approximately along longitude 70 degrees E. To date no hypothesis for this intriguing distribution pattern has been put forward. We detected molecular footprints in the contemporary genetic composition in nuclear DNA (ITS1, ITS2) and chloroplast DNA (trnL-trnF spacer region) of the steppe element Clausia aprica (Brassicaceae) providing evidence for a severe longitudinal range split and genetic differentiation east of the Ural Mountains about 1 million years ago caused by Quaternary climatic oscillations. Clausia aprica provides the first phylogeographical analysis on the intraspecific evolution of an Eurasian steppe plant.

Asia↗
PubMed2004

Catheter based intracoronary brachytherapy leads to increased platelet activation.

BACKGROUND: Vascular brachytherapy (VBT) after percutaneous coronary intervention (PCI) is associated with a higher risk of stent thrombosis than conventional treatment. OBJECTIVE: To investigate in vivo periprocedural platelet activation with and without VBT, and to assess a possible direct effect of radiation on platelet activation. DESIGN: Of 50 patients with stable angina, 23 received VBT after PCI, while 27 had PCI only. The 23 patients who received VBT after PCI were pretreated for one month with aspirin and clopidogrel. Platelet activation was assessed by flow cytometry. RESULTS: The two patient groups did not differ in their platelet activation before the intervention. There was a significant increase in activation immediately after VBT, with 21.2% (interquartile range 13.0% to 37.6%) thrombospondin positive and 54.0% (42.3% to 63.6%) CD 63 positive platelets compared with 12.7% (9.8% to 14.9%) thrombospondin positive and 37.9% (33.2% to 45.2%) CD 63 positive platelets before the intervention (p < 0.001 and p < 0.01, respectively). Patients without VBT had no periprocedural difference in platelet activation immediately after PCI. No increase in platelet activation was found after ex vivo irradiation of blood samples obtained from healthy controls. CONCLUSIONS: Catheter based intracoronary VBT carried out according to current standards is highly thrombogenic. The current antithrombotic treatment with aspirin and clopidogrel is not sufficient to suppress platelet activation during the procedure. From in vitro experiments, it appears that platelet activation during brachytherapy is not caused by irradiation but by the procedure of catheter based VBT.

Angina Pectoris↗
PubMed2004

Evaluation of the long-term pancreatic effects of constitutive nitric oxide synthase inhibition in dogs.

Constitutive and inducible isoforms of nitric oxide synthase (NOS) catalyze the synthesis of nitric oxide (NO) from L-arginine in various tissues and in different pathophysiologic states. Short-term treatment with NOS inhibitors has been associated with pancreatic enzyme elevations and pancreatic acinar cell degeneration; however, long-term pancreatic effects of NOS inhibition are not known. The purpose of this study was to evaluate the subchronic pancreatic effects of L-nitro-arginine (LNA), a compound that preferentially inhibits constitutive NOS isoforms. LNA was administered orally at doses of 10 and 30 mg/kg per day to 6 female dogs/group for 4 weeks. To differentiate whether the pancreatic effects of LNA may be related to its arginine structure, an additional group was given L-arginine (L-Arg) at plasma concentrations similar to the high dose of LNA (30 mg/kg per day). Pancreatic effects were monitored by changes in serum levels of pancreatic enzymes at regular intervals and by microscopic examinations at the end of the study. Both LNA and L-Arg were systematically available throughout the 4-week study period. LNA produced dose-related elevations (1.3-10-fold above concurrent control) in serum levels of pancreatic enzymes (amylase, lipase and trypsin-like immunoreactivity) during the 4-week treatment period with peak elevations occurring during the first week. Histologic assessments of the pancreas conducted at the end of the 4-week dosing period were unremarkable. Additionally, LNA treatment resulted in reduction in heart rate (40%), gastric distension and gastric mucosal erosion and ulceration. No pancreatic, cardiac, or gastric effects were seen with L-Arg, indicating that above effects were likely due to NOS inhibition. Results of this study confirmed previous observations of acute pancreatic alterations following the inhibition of constitutive NOS isoforms. However, these pancreatic alterations appear to be only transient effects as elevations in serum enzymes declined over time and no structural acinar cell damage was seen after continuous treatment with LNA for 4 weeks, suggesting an adaptation to NOS inhibition over time.

Amylases↗
PubMed2004

Effect of lameness on culling in dairy cows.

The purpose of this study was to assess the effect of lameness on dairy cow survival. Cox's proportional hazards regression models were fitted to single-lactation data from 2520 cows in 2 New York State dairy herds. Models were controlled for the time-independent effects of parity, projected milk yield, and calving season, and for the time-dependent effects of lameness and culling. Other common diseases were found to be nonconfounding and so were not included in any of the final models. Survival was measured as the time from calving until death or sale. Cows were censored if they reached the start of the next lactation or end of the study, whichever occurred first. All models were stratified by herd. For all lameness diagnoses combined, survival in the herd decreased for those cows becoming lame during the first half of lactation, with a hazard ratio of up to 2 times that of a nonlame cow. Foot rot diagnosed during the second or third months of lactation decreased survival during the same time period (hazard ratio=5.1; 95% confidence interval=1.6 to 16.2). Sole ulcers diagnosed in the first 4 mo of lactation decreased survival in several subsequent periods in which the strongest association was between diagnosis in the third and fourth months of lactation and exit from the herd during that same period (hazard ratio=2.7; 95% confidence interval=1.3 to 6.0). Foot warts were not associated with decreased survival in this analysis. Lameness was never associated with increased survival in any of the models.

Animal Husbandry↗
PubMed2003

Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation.

Telomere maintenance is a prerequisite for immortalisation, and in most malignant cells is carried out by telomerase, an enzyme that synthesis new telomeric repeats on the chromosome ends. In normal or reactive tissues with a high regenerative capacity, telomerase is regulated according to the telomere loss that occurs during proliferation. To evaluate the interaction of proliferation and telomerase activity in malignant lymphomas, we quantified telomerase expression in different non-Hodgkin lymphomas in comparison to normal or reactive lymph nodes. Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes. Significantly higher activity was detected only in Burkitt's lymphoma. Telomerase activity correlated well with hTERT and c-myc expression, but was independent of proliferation. To evaluate interactions of telomere-binding protein expression on telomerase expression in non-Hodgkin lymphoma, the mRNA levels of TRF1, TRF2, tankyrase and hPif1 were assessed by real-time RT-PCR. We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation. Telomerase regulation in non-Hodgkin lymphomas is therefore uncoupled from proliferative stimuli found in reactive lymphoid tissue. We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

Biomarkers, Tumor↗
PubMed2003

Anticoagulation with the low-molecular-weight heparin dalteparin (Fragmin) in atrial fibrillation and TEE-guided cardioversion.

BACKGROUND: Cardioversion (CV) in atrial fibrillation can cause arterial embolism. Effective anticoagulation clearly reduces the risk. In practice, in every third case anticoagulation is not in line with the recommendations. Simplification can be achieved, and time gained, by transesophageal echocardiography (TEE) due to the shorter anticoagulation period prior to CV, and by use of low-molecular-weight heparin (LMWH) for anticoagulation. As yet little data is available on LMWH in cardioversion. The aim of this cohort study was to investigate the administration of a LMWH in this indication under everyday clinical conditions. METHODS: 125 patients treated as inpatients for atrial fibrillation or -flutter received the LMWH Fragmin (dalteparin 2 x 100 anti-Xa units/kg, maximum dosage 2 x 10,000 anti-Xa units subcutaneously). In the presence of a relevant indication, TEE-guided CV was performed. The application of dalteparin was terminated as soon as effective anticoagulation had been achieved from phenprocoumon or once anticoagulation was no longer indicated. RESULTS: 125 patients with atrial fibrillation or -flutter received dalteparin for a median of 11 days (range of 3-41 days). TEE was performed in 39 patients. Five patients revealed a thrombus in the left atrial appendage in the TEE, and one patient died from suspected cerebral embolism over the further course. In the remaining 124 patients, no thromboembolic event was established. Successfully cardioverted were 26 of 34 patients (76%) who had no thrombus in the TEE. Serious adverse effects did not ensue. CONCLUSION: Simple, well tolerated and effective anticoagulation is possible with dalteparin in TEE-guided CV. Due to the methodic limitations of a cohort study and the low incidence of emboli, the efficacy of dalteparin in this indication needs to be further confirmed by prospective and randomized studies.

Administration, Oral↗