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J van de Loo

Publications and source records attributed to J van de Loo.

At least 19 recordsLinked to original sources
PubMed1999

Lovastatin induces p21WAF1/Cip1 in human vascular smooth muscle cells: influence on protein phosphorylation, cell cycle, induction of apoptosis, and growth inhibition.

Morbidity, mortality and the incidence of myocardial revascularisation procedures can be reduced by simvastatin, an inhibitor of the HMG-CoA reductase (EC 1.1.1.34). It was hypothesised that inhibition of isoprenylation of signalling proteins by HMG-CoA reductase inhibitors (vastatins), especially of the p21ras proteins could be causative for suppression of vascular smooth muscle cell (SMC) proliferation. The primary pharmacological mechanism of vastatins on human vascular SMC still remains unexplained. To analyse the influence of vastatins, SMC grown in presence of endothelial cell growth supplement (ECGS) were exposed to different concentrations of lovastatin. At 10 microM concentration, inhibition of SMC proliferation was associated with induction of apoptosis in a large fraction of cells as at the 1 microM level apoptosis was induced only in a minority of SMC. Protein phosphorylation on tyrosine, serine and threonine residues demonstrated no differences to untreated controls. Lovastatin induced arrest of cells in G0/G1 phase of the cell cycle and DNA synthesis was reduced. Western blot analysis demonstrated a significant induction of p21WAF1/Cip1 protein expression. This led to strong inhibition of cyclin dependent kinases (cdks) resulting in a cell cycle arrest. Our study provides evidence for a pharmacological explanation for the inhibition of ECGS-driven proliferation of human SMC by lovastatin.

Apoptosis↗
PubMed1998

Quality of life in adult patients with acute myeloid leukemia receiving intensive and prolonged chemotherapy -- a longitudinal study.

Intensification of treatment for acute myeloid leukemia (AML) in adult patients resulted in a substantial improvement in long-term prognosis. Therefore, the assessment of quality of life (QL) of patients undergoing treatment is of growing interest. This study was designed to evaluate QL in patients with AML treated according to the protocol of the German AML-Cooperative Group (Münster, Germany). The EORTC QLQ-C 30 questionnaire was used to analyze QL throughout therapy, evaluating defined specific parameters at 12 different time-points. Sixty-one patients were recruited within the first 30 months of the study. Those 28 patients who have completed the course of inpatient treatment (n=28) are evaluated for changes in the conceptually distinct QL domains: Physical Functioning (P<0.001), Role Functioning (P=0.001), Emotional Functioning (P < 0.001) and Social Functioning (P=0.007) improve significantly from beginning of chemotherapy to the end of inpatient treatment. Individual assessment of Global Health Status and Subjective QL improves significantly over the same time (P< 0.001). At the end of inpatient treatment patients suffer significantly less from fatigue, nausea/emesis, loss of appetite and sleep disturbance (P < 0.001). Although most patients with AML eventually relapse, the evaluation of QL in patients undergoing treatment shows that subjective benefit outweighs the adverse effects of antileukemic therapy.

Acute Disease↗
PubMed1998

The molecular basis of antithrombin deficiency in Belgian and Dutch families.

The molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed. DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intron-exon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.

Adolescent↗
PubMed1997

Efficacy and kinetics of bone marrow processing and enrichment of haematopoietic progenitor cells (HPC) by a large-volume apheresis procedure.

We investigated the efficacy of bone marrow (BM) processing by an automated large-volume apheresis procedure (6 x original BM volume) in 10 paediatric and adult patients undergoing BM harvesting before myeloablative therapy. Volume-dependent kinetics during apheresis were analyzed by sequential collection of processed cells into a six-fold collection bag system with consecutive analysis of the single bags. BM processing resulted in an 83.3% (+/- 21) recovery of mononuclear cells (MNC), a 97.9% (+/- 1.1) reduction of erythrocytes (RBC) and a 87.7% (+/- 2.9) volume reduction. To determine volume-dependent kinetics of haematopoietic progenitor cell (HPC) enrichment during apheresis, leukocytes (WBC), mononuclear cells (MNC), CD34 cells and colony-forming cells (CFU-GM) were serially quantitated in subsequent collection bags. Large-volume BM processing significantly enhanced absolute yields of CD34+ cells (mean: 4.01 (+/- 2.81) x 10(6)/kg bw) and CFU-GM (mean: 1.92 (+/- 1.47) x 10(4)/kg bw) compared with the standard procedure (3 x BM volume) by 26.9% (+/- 10.9) and 27.2% (+/- 11.6), respectively. We concluded that large-volume apheresis for BM processing is an efficient technique significantly improving the yields of haematopoietic progenitor cells (HPC) without any relevant changes in the purity of the final product. Moreover, sequential collection and analysis of HPC represents a good model to investigate the volume-dependent kinetics and efficacy of BM processing.

Adolescent↗
PubMed1997

Coagulation factor VII and the risk of coronary heart disease in healthy men.

Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease (CHD). A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity (FVIIc). Significant associations of FVIIc with increased coronary risk, however, have been found only in the Northwick Park Heart Study. Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospective Cardiovascular Münster study. In the study population (age at entry, 49.3 +/- 6.1 years, mean +/- SD), 130 CHD events occurred during follow-up. FVIIc was significantly higher in subjects with coronary events than in those without (112.4 +/- 20.1% vs 108.7 +/- 21.4%, P = .023). Compared with individuals without coronary events, FVIIc was not significantly higher in men with nonfatal events (111.7 +/- 20.4%; P = .196, n = 93), but there was a tendency toward higher FVIIc activity in subjects with fatal events (114.6 +/- 19.5%; P = .076, n = 37). In the multiple logistic regression analysis, we did not find FVIIc to be an independent risk factor for CHD, and the significance of FVIIc disappeared after total cholesterol, LDL-cholesterol, and triglycerides were taken into account. The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors: smoking; myocardial infarction events in family; angina pectoris; high levels of fibrinogen, total cholesterol, LDL cholesterol, and triglycerides; and a low level of HDL cholesterol. We conclude that FVIIc is a risk factor for CHD, especially in the presence of additional risk factors, and must be taken into account when assessing cardiovascular risk in men.

Adult↗
PubMed1996

[Successful multimodal therapy of a locally advanced non-small-cell bronchial cancer].

HISTORY AND CLINICAL FINDINGS: A chest radiogram, performed on a 60-year-old man with unproductive cough for 3 months, showed a space-occupying lesion in the right upper lobe, and breath sounds were diminished in this area. He had been a heavy smoker. His general condition and nutritional state were good. INVESTIGATIONS: Computed tomography, skeletal scintigraphy, bronchoscopy with biopsy and mediastinoscopy established the diagnosis of a locally advanced non-small-cell bronchial carcinoma (stage IIIB or T2N3M0). TREATMENT AND COURSE: Combined adjuvant treatment was begun in the hope of improving the median survival time of 8 months predicted for this tumour stage. After two cycles of a combined chemotherapy scheme (ifosfamide, carboplatin, etoposide) he received hyperfractionated-accelerated radiotherapy (total dose 45 Gy; 1.5 Gy twice daily) together with carboplatin and vindesine. This was followed by a right upper lobectomy with lymphadenectomy. Full remission was confirmed in both the resected specimen and the lymph nodes. The patients remains free of tumour 30 months after the diagnosis. CONCLUSION: Neoadjuvant treatment can significantly improve the prognosis of non-small-cell bronchial carcinoma in stage III. Such patients should therefore be treated according to the appropriate study protocol, if possible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Bronchiolitis obliterans with organizing pneumonia: differential diagnosis of pneumonia refractory to antibiotics].

HISTORY AND FINDINGS: A previously healthy 58-year-old woman was admitted with rapidly worsening dyspnoea, dry cough and subfebrile temperature. Chest radiogram showed spotty infiltrations, especially in the bases of both lungs. She was dyspnoic with mild tachypnoea (24/min) and mild cyanosis of the lips. Fine, non-resonant rales were heard over the middle and lower lobes bilaterally. INVESTIGATIONS: Erythrocyte sedimentation rate was markedly raised (97/110 mm), arterial oxygen partial pressure slightly decreased (45 mm Hg), CO2 partial pressure was 32 mm Hg. Bronchoalveolar lavage was unremarkable. TREATMENT AND COURSE: Because of the respiratory impairment broad antibiotic treatment was at once commenced empirically with gentamycin, cefotaxim, erythromycin, rifampicin and fluconazole. As the response was poor, a transbronchial lung biopsy was performed. This merely showed nonspecific lymphoplasmacellular bronchitis. An open biopsy then revealed bronchiolitis obliterans with organizing pneumonia (BOOP). Treatment with initially 75 mg prednisone daily quickly brought about improvement and the patient was entirely well after 6 months. CONCLUSION: The described constellation of history and clinical as well as radiological findings should strongly suggest BOOP. With adequate treatment the prognosis is excellent.

Anti-Bacterial Agents↗
PubMed1996

Hospital-acquired candida and aspergillus pneumonia--diagnostic approaches and clinical findings.

Bronchoscopy with bronchoalveolar lavage (BAL), collection of bronchial secretions (BS) and/or high resolution computed tomography (CT) of the lungs was performed in 70 patients with candida and/or aspergillus pneumonia. The sensitivity of bronchoscopy in detecting histologically proven fungal disease was 59%. Characteristic CT signs were found in 11 of 14 patients with candida pneumonia and 16 of 19 patients with aspergillosis. The more frequent use of bronchoscopy and CT scans between 1990 and 1992 compared with 1986-1989 for the differential diagnosis of new pulmonary infiltrates in immunocompromised patients resulted in earlier antifungal treatment (14 vs. nine days; P < 0 center dot 025). In the second treatment period survival was improved from 36 to 50% (not significant). Bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools and should be performed as early as possible in the course of pneumonia in patients at high risk of fungal diseases.

Adolescent↗
PubMed1996

Thrombospondin measured in whole blood--an indicator of platelet activation.

Abnormal platelet activation may be involved in prethrombotic states and lead to thromboembolism. When platelets become activated, they release thrombospondin (TSP) from their alpha-granules which binds mainly to the surface of activated platelets, platelet-derived microparticles and other blood cells. To determine bound as well as free TSP in a single assay, we developed an indirect ELISA to measure TSP in fixed whole blood. The intra-assay variance was less than 5% and 97% of purified standard TSP, added to whole blood samples, was recovered with the ELISA. Blood collected with a 20G needle into a syringe resulted in lower "whole blood TSP' values than blood collected with the Vacutainer system. Whole blood TSP levels were measured in 66 healthy blood donors (20F, 46M) aged 25-75 years. The mean whole blood TSP concentration was 33 +/- 19 ng/ml. No significant difference in whole blood TSP was found between healthy females and males (35 +/- 23 ng/ml vs. 33 +/- 17 ng/ml).

Adult↗
PubMed1996

[Quality of life and coping with illness in patients with acute myeloid leukemia].

Advances in chemotherapy significantly prolong survival of patients with acute myeloid leukemia (AML) and may cure a significant percentage of patients. Therefore, the assessment of quality of life (QL) of patients undergoing chemotherapy is of growing interest. This study was designed to evaluate QL in patients with AML treated according to the protocol of the German AML-Cooperative Group (Münster, FRG). Based on conceptual, methodological and practical criteria, the EORTC-QLQ C 30 questionnaire was used. In addition, patients' coping strategies were assessed by the FQCI. Patients' individual perception of their disease and therapy was evaluated by a semi-structured interview. Currently, 61 patients are enrolled in the protocol. For those patients having completed the course of inpatient treatment, individual assessment of Global Health Status and Subjective QL improves significantly. The content analysis of the interviews shows to what extent aspects of the inpatient setting influence patients' QL. Although only a minority of patients with AML remain in continuous complete remission, the evaluation of QL in patients undergoing treatment shows that subjective benefit outweighs the effects of antileukemic therapy.

Adaptation, Psychological↗
PubMed1995

Differential cell count and lymphocyte subsets in bronchoalveolar lavage during pneumonia with and without peripheral neutropenia.

One hundred immunocompromised HIV negative patients with microbiologically positive pneumonia underwent bronchoalveolar lavage (BAL) studies. Thirty cases showed peripheral neutropenia (< 1000 neutrophils/microL), 70 did not. The total cell number in BAL, the differential cell counts, and the lymphocyte subsets (CD4, CD8, CD19, CD57) were measured. Patients with pneumonia and normal or elevated peripheral neutrophils had a significantly increased total number of cells in BAL compared to patients with peripheral neutropenia (3.2 +/- 2 vs 1.3 +/- 0.6 x 10(5) cells/ml2 lavage fluid, p < 0.01). Ninety percent of the BAL differential cell counts obtained in patients exceeding 1000 neutrophils/microL showed a lymphocytic and/or neutrophilic alveolitis, whereas only 54% of patients with peripheral neutropenia displayed abnormal counts (p < 0.01). Yet the typical pattern of neutrophilic alveolitis was found more often for peripheral neutrophil counts over 1000/microL with high significance (p < 0.0001). Abnormal BAL cell patterns for neutropenic patients uniformly showed a lymphocytic alveolitis, only 10% additionally conformed with the pattern of neutrophilic alveolitis. Patients with pneumonia with and without peripheral neutropenia had similar findings in BAL lymphocyte subsets and exhibited a reduced CD4/CD8 ratio compared to controls (p < 0.05). The high susceptibility of severe neutropenic patients to pulmonary, especially fungal infections may be explained by the local lack of neutrophils.

Adolescent↗
PubMed1995

Pulmonary fungal infections in patients with hematological malignancies--diagnostic approaches.

In a retrospective study of 56 patients with hematological malignancies and fungal pneumonia we have analyzed the value of different diagnostic procedures. In all patients (Candida n = 29, Aspergillus n = 23, mixed fungal infection n = 4) bronchoscopy and/or high-resolution computed tomography of the lungs was performed. Cultural detection of fungi in bronchoalveolar lavage was successful in 23/32 Candida and 11/23 Aspergillus pneumonias. Other relevant pathogens were identified by bronchoscopy in 21 cases. Thorax CT scans showed diagnostic evidence of fungal pneumonia in 10/13 Candida and in 16/18 Aspergillus infections. Blood cultures were positive in 9/33 Candida pneumonias and in none of aspergillosis cases. Serological testing and surveillance cultures had only limited value for the early diagnosis of pulmonary mycosis. Our data suggest that bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools with high sensitivity in patients with hematological malignancies and new pulmonary infiltrates. These procedures facilitate the early and reliable recognition of invasive fungal disease which may have a bearing on the initiation, length, and differential therapy of antimycotic drugs.

Adolescent↗
PubMed1995

Pulmonary infiltrates in patients with haematologic malignancies: clinical usefulness of non-invasive bronchoscopic procedures.

In a prospective study 90 patients with haematologic malignancies (57 acute leukaemias, 6 Hodgkin's Diseases, 15 Non-Hodgkin Lymphomas, 12 other diseases), with fever exceeding 38.4 degrees C and newly developed pulmonary infiltrates underwent bronchoscopy obtaining bronchoalveolar lavage, bronchial washings and protected brush specimen (n = 71). Pneumonias due to gram-negative bacteria (n = 38) and fungi (n = 34) were most frequent. Bronchoscopic specimens yielded 226 isolates (2 different organisms/bronchoscopy on average). 112 organisms were finally regarded as causing pneumonia. Sensitivity of bronchoscopy in diagnosing infectious episodes was 66%, but only 4 out of 13 non-infectious pulmonary infiltrates could be identified. Bronchoscopy was most effective in the diagnosis of pneumocystis carinii and herpes virus pneumonia, whereas sensitivity and specificity of detecting fungal and bacterial pneumonia were low. Empirical antimicrobial therapy was verified by evaluation of bronchoscopic samples in 25 out of 90 cases. Empirical therapy was successfully changed according to the results of invasive samplings in 34 out of 90 cases. Early identification of causative pathogens had a significant impact on survival.

Adolescent↗