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Biomedical subjects

P C Huijgens

Publications and source records attributed to P C Huijgens.

At least 19 recordsLinked to original sources
PubMed2006

[Stem cells: hype and hope].

There is increasing interest in the use of stem cells for therapeutic purposes. The use of embryonic stem cells carries ethical and legal restrictions that limit their role in tissue regeneration. These restrictions do not apply to somatic stem cells, such as haematopoietic stem cells, which normally reside in the bone marrow. Preclinical studies have produced very promising results using these cells in experimental models of myocardial infarction. Bone-marrow cells have also been used to generate several different types of tissue. However, experimental data suggest that bone marrow also houses other non-haematopoietic stem cells, which could account for the alleged plasticity of haematopoietic stem cells. So far, the results of randomised clinical trials in patients with myocardial infarction or heart failure have been disappointing. It is clear that further research in this field is needed.

Animals↗
PubMed2005

[Radio-immunotherapy for B-cell non-Hodgkin lymphoma].

Radio-immunotherapy is a new treatment modality for patients with B-cell non-Hodgkin lymphoma. In radio-immunotherapy, a therapeutic radionuclide is coupled to a monoclonal antibody directed against a tumour-specific or tumour-associated antigen. Biodistribution studies and dosimetry are used in the planning of radio-immunotherapy. Clinical studies, notably in patients with indolent non-Hodgkin lymphoma, have demonstrated the clinical feasibility and efficacy of this treatment. The use of a high dose ofradio-immunotherapy in combination with (high-dose) chemotherapy and peripheral stem-cell transplantation constitutes a supplemental treatment for patients who respond insufficiently or not at all to standard therapy. The exact place of radio-immunotherapy in the treatment of patients with non-Hodgkin lymphomas is not yet clear.

Chemotherapy, Adjuvant↗
PubMed2005

[Clinical reasoning and decision-marking in practice. A general practitioner with long-standing anaemia].

In order to calibrate his haemoglobin meter, a general practitioner had his own haemoglobin level checked regularly at a nearby laboratory. At 37 years of age, one of these assays revealed 7,0 mmol/l. Because he had no symptoms, he prescribed himself iron-substitution therapy but the haemoglobin concentration did not normalise. At 52 years of age, the patient increasingly suffered from fatigue and exertional dyspnoea and had intermittent abdominal pain, distension and rumbling. Biopsies of the small intestine revealed crypt hypertrophy and intraepithelial lymphocytosis: signs ofcoeliac disease. The symptoms disappeared when the patient started to use a gluten-free diet. The haemoglobin level also normalised. Coeliac disease must be considered in the differential diagnosis of iron-deficiency anaemia.

Adult↗
PubMed2005

[Modern treatment methods for multiple myeloma: guidelines from the Dutch Haemato-Oncology Association (HOVON)].

The treatment for multiple myeloma has undergone many changes over the past decade. Intensive therapy with autologous stem-cell support has improved the clinical outcome significantly in younger patients. Reduced intensity conditioning regimens have lowered the high treatment-related mortality of myeloablative allogeneic transplantation. New effective anti-myeloma drugs such as bortezomib and thalidomide analogues have become available. These new developments have made it necessary to formulate recommendations to facilitate decisions concerning the management of myeloma patients. The Myeloma Working Party of the Dutch Haemato-Oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland) has developed therapy guidelines based on phase-II and phase-III studies as well as the expertise of the working party. These include upfront induction therapy followed by autologous transplantation for patients aged up to 65 years and oral melphalanprednisone treatment for patients with severe co-morbidities and patients over the age of 65 years. Patients under the age of 66 with an HLA-identical (family) donor are candidates for non-myeloablative stem-cell transplantation following autologous stem-cell transplantation. For second-line treatment, thalidomide, combined with dexamethasone is recommended. Younger patients responding to second-line treatment are candidates for a second autologous transplant. Bortezomib is indicated for those patients refractory to the previous two lines of treatment. All patients should receive long-term bisphosphonates. Erythropoietin may be considered in symptomatic anaemia as well as antibiotic prophylaxis during induction therapy which includes dexamethasone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Dose-related vincristine-induced peripheral neuropathy with unexpected off-therapy worsening.

This study describes the natural course of vincristine-induced peripheral neuropathy in patients with lymphoma (n = 114) receiving vincristine in two different dose intensities. Neuropathic changes were observed in both dose intensity groups, but the higher dose intensity group reported significantly more symptoms during therapy, whereas neurologic signs were significantly more prominent after a cumulative dose of 12 mg vincristine. Furthermore, off-therapy worsening of symptoms (24%) and signs (30%) occurred unexpectedly.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Characteristics of 40 primary extranodal non-Hodgkin lymphomas of the oral cavity in perspective of the new WHO classification and the International Prognostic Index.

Non-Hodgkin lymphomas (NHLs) are often present outside the lymph nodes. Although primary extranodal NHLs (PE-NHL) form a substantial part of all NHLs, reports on oral PE-NHLs are rare. Forty patients with PE-NHL of the oral cavity have been studied for the distribution of gender, age, oral subsite and presenting complaint, histological subtype according to the WHO classification, clinical stage, treatment, and follow-up. The data are reviewed against the background of the literature. Furthermore, the International Prognostic Index has been taken into consideration. All patients had a lymphoma of B-cell lineage. Two-thirds of patients presented with locoregional disease. Mean survival time was 38 months, with a mean recurrence-free survival time of 31 months. There was no statistically significant difference in survival time between patients with bone versus soft tissue localisation of the PE-NHL. In view of the rarity of PE-NHL involving the oral region multicenter studies are needed for evaluation of the usefulness of the International Prognostic Index for non-Hodgkin lymphoma in this particular part of the body.

Adolescent↗
PubMed2005

Health related quality of life in patients with multiple myeloma undergoing a double transplantation.

OBJECTIVES: To investigate the subjective well-being of patients with newly diagnosed multiple myeloma who were treated in a tandem transplantation programme. METHODS: Fifty-one patients participated in the prospective, longitudinal questionnaire study. The EORTC QLQ-C30 and the EuroQol-5D were administered 2 wk after completion of vincristine, adriamycin and dexamethason/vincristine, adriamycin and methyl prednison (VAD/VAMP) chemotherapy, both at hospital discharge after treatment with high-dose melphalan (HDM) and 1 month after this hospital discharge, at hospital admission, at the day of hospital discharge for peripheral stem cell transplantation (PSCT) and at 6 and 12 months following discharge after PSCT. RESULTS: Overall, patients' functioning improved during treatment and follow-up, with significant decreases shortly following PSCT. Shortly after HDM and PSCT, patients reported a considerable increase in levels of soreness in the mouth (+26/+36 points on a scale ranging form 0 to 100; P < 0.01), change of taste (+23/+21 points; P < 0.05/NS), nausea/vomiting (+26/+27 points; P < 0.01/< 0.05), appetite loss (+40/+43 points; P < 0.001) and diarrhoea (+25/+36 points; P < 0.01). However, none of these symptoms persisted during follow-up. CONCLUSION: The intensive treatment programme was subjectively being well tolerated by the majority of patients. The duration of declined quality of life after administration of HDM seemed to be short. The duration of subjective recovery after PSCT remained uncertain, but in any case was present at the 6 month follow-up. Together with the rather good results in survival, the evaluation of quality of life invites further exploration of double transplantations in multiple myeloma.

Adult↗
PubMed2005

Cost-effectiveness of rituximab (MabThera) in diffuse large B-cell lymphoma in The Netherlands.

OBJECTIVE: To determine the incremental cost-effectiveness ratio (ICER) of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) vs. CHOP plus rituximab (R-CHOP) in diffuse large B-cell lymphoma (DLBCL) patients in the Netherlands. METHODS: A state transition model was developed to estimate the clinical course, costs and quality of life of patients with stage II, III or IV DLBCL receiving initial treatment with CHOP or R-CHOP to arrive at the ICER. The base year for the cost analysis was 2002 and was performed from the societal perspective. Only direct medical costs were included. The time horizon of the model was 15 yr and both costs and effects were discounted at 4%. Sensitivity analyses were performed to determine the effect of varying base-line assumptions of the model. RESULTS: The incremental gain in quality adjusted life years (QALYs) was 0.88 in both the younger and the older patient groups. The costs were 12 343 higher in the younger group of patients and 15 860 in the older patients. This resulted in an ICER of 13 983 for the younger and 17 933 for the older patients per QALY gained. These results were sensitive to the time horizon of the model, other variations had a marginal impact on the outcome. CONCLUSION: The addition of rituximab to standard therapy for DLBCL results in a gain of 0.88 QALYs. The ICER of 13 983 for younger and 17 933 for older patients per QALY gained should, seen in the light of disease severity, be considered acceptable by most policy makers in priority setting for budget allocation.

Antibodies, Monoclonal↗
PubMed2005

Reduced-intensity conditioning regimens in malignant haematological diseases.

Allogeneic stem cell transplantation is a potentially curative procedure for patients with haematological malignancies. Conventional, myeloablative conditioning is, however, poorly tolerated by patients of advanced age, those receiving second transplants and those with concomitant diseases. Based on recognition of the importance of a graft-versus-disease (GVD) effect in curing malignant haematological disease, reduced intensity conditioning (RIC) as preparation for allogeneic stem cell transplantation has been developed for these patients. Although large prospective randomised clinical trials with significant follow-up are lacking, transplant-related morbidity and mortality of RIC transplants seem to compare favourably with conventional conditioning in this group of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

[The Dutch Health Council report on haemopoietic stem cells].

The Dutch Health Council advised the government on the use of haemopoietic stem cells in clinical medicine in September 2003. Most stem cell transplantations (SCTs) are performed in closely co-operating centres for haematological intensive care, and these centres are required to have a license from the government. The introduction of non-myeloablative SCT, exploiting the immunological effects of donor T cells, extends the variety of diseases for which SCT is a useful treatment option, as well as extending the age limits. The capacity of the centres appears to be sufficient, but their finances are not. This, together with strict adherence to accepted indications, is probably one of the main reasons why the number of SCTs performed in the Netherlands is rather low as compared to other European countries. The Council stresses that the harvesting and handling of umbilical cord stem cells is a public rather than a private matter, with the purpose of creating a bank for these preparations from which patients may benefit if the need so dictates. The Council pleads for support to advance the basic research on stem cells and the immunological aspects of stem cell transplantation.

Critical Care↗
PubMed2004

Lack of neuroprotection by an ACTH (4-9) analogue. A randomized trial in patients treated with vincristine for Hodgkin's or non-Hodgkin's lymphoma.

PURPOSE: This randomized, double-blind, placebo-controlled study evaluates the effect of the corticotropin (4-9) analogue Org 2766 on the neuropathy-free interval in patients receiving vincristine (VCR) containing chemotherapy for Hodgkin's or non-Hodgkin's lymphoma. PATIENTS AND METHODS: In a longitudinal design, 150 patients were evaluated by interview, neurological examination, and neurophysiological techniques. Patients with an expected cumulative VCR dose of at least 8 mg received a single dose of Org 2766 or placebo before and after each intravenous VCR injection and 3-4 weeks after cessation of VCR. The final patient assessment was performed 1 month after discontinuation of study medication. The neuropathy-free interval as the major end point of this study was defined as the first occurrence of bilateral paresthesias and expressed as the administered cumulative VCR dose. This bi-center study represents the largest cohort of patients monitored for the effect of an ACTH-analogue on VCR neurotoxicity. RESULTS: A total of 147 patients were included in the final analysis. No significant differences were observed between the placebo and actively treated group for the major and secondary endpoints. CONCLUSION: Contrary to a single previous pilot study in patients receiving VCR-based chemotherapy, in our study the ACTH (4-9) analogue Org 2766 did not provide protection from VCR-induced neuropathy.

Adrenocorticotropic Hormone↗
PubMed2004

Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies.

Gram-positive breakthrough infections pose a major drawback to the use of quinolones for antibacterial prophylaxis in neutropenic patients. Levofloxacin offers the advantage of an augmented Gram-positive spectrum and may potentially overcome this problem. In an open-label, clinical pilot study, we investigated the effects on throat and bowel microflora and pharmacokinetics of a once-daily oral dose of 500 mg levofloxacin, during neutropenia in 20 patients with haematological malignancies. Gram-negative bowel flora and Staphylococcus aureus were successfully eradicated. No Gram-negative infections occurred. Minimal inhibitory concentration values for viridans group (VG) streptococci tended to increase, in four patients over 8 mg/l, indicating resistance to levofloxacin. Four patients developed blood-stream infections with levofloxacin-resistant Gram-positive cocci. No significant changes in numbers of anaerobic microorganisms were observed. Pharmacokinetic parameters of levofloxacin, including the maximum serum concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve (AUC), volume of distribution at steady state (V(ss)/F) and clearance (CL/F) were not statistically different at first dose and during neutropenia. In conclusion, levofloxacin eradicates Gram-negative microorganisms and S. aureus and spares the anaerobic flora. Its pharmacokinetic profile is unaltered during neutropenia. However, prolonged administration of levofloxacin as antibacterial prophylaxis may be hampered by the emergence of levofloxacin-resistant VG streptococci.

Administration, Oral↗
PubMed2004

Correlation between the extent of platelet activation in platelet concentrates and in vitro and in vivo parameters.

BACKGROUND AND OBJECTIVES: Platelet activation, which is necessary to stop bleeding, also occurs in vitro during the storage of platelet concentrates (PCs). However, it is unknown whether in vitro-activated platelets are able to reduce blood loss in the patient. We studied correlations between platelet activation in PCs and in vitro parameters (pH, platelet count, swirling effect, storage time). In addition, we studied the correlation between platelet activation and in vivo parameters [the volume of thorax drain fluid as a measure of blood loss, platelet count, international normalized ratio (INR), and activated partial thrombin time (APTT)] in a clinical pilot study. MATERIALS AND METHODS: White blood cell-reduced PCs prepared from five buffy coats and one plasma unit (n = 55; storage time: median, 5 days; range, 2-12 days) were sampled. Platelet activation (CD62p, CD63, CD42b), as measured by flow cytometry, pH, platelet count, swirling effect and storage time, was determined. For the in vivo pilot study, PCs (n = 21) stored for 2-7 days were also checked for the above parameters and transfused into patients (n = 21) immediately after coronary artery bypass graft surgery. The volume of thorax drain fluid was measured for up to 12 h after surgery, and the platelet count, INR and APTT were measured < 1 h and 16-24 h postsurgery. RESULTS: A good correlation (r2 > 0.5) was observed between CD62p and CD63, between CD62p and CD42b, between CD62p or CD63 and pH and between CD62p or CD63 and swirling effect. Also, a significant increase in platelet activation was observed for PCs stored for > or = 8 days (mean +/- standard deviation: CD62p, 41.6 +/- 30.7; CD63, 23.8 +/- 18.6), compared to PCs stored for 2-7 days (mean +/- standard deviation: CD62p, 12.3 +/- 4.8; CD63, 10.4 +/- 3.6). No correlation (r2 < or = 0.1) was observed between platelet activation and the in vivo parameters. CONCLUSIONS: Although a correlation between platelet activation and in vitro parameters was observed, no correlation was found between platelet activation and in vivo parameters. Possible explanations for this are a too low variance in platelet activation in transfused PCs, and too small a number of patients.

Antigens, CD↗
PubMed2004

Development of white blood cell fragments, during the preparation and storage of platelet concentrates, as measured by using real-time polymerase chain reaction.

BACKGROUND AND OBJECTIVES: White blood cell (WBC) fragments may cause human leucocyte antigen (HLA) immunization in recipients. We investigated the occurrence and production of WBC fragments in platelet concentrates (PCs) and plasma units, during storage and filtration, by using real-time polymerase chain reaction (PCR) and flow cytometry. MATERIALS AND METHODS: To study the occurrence of WBC fragments, 'male' WBCs were spiked into double-filtered 'female' PCs in a concentration series of 0.03-100 WBCs/microl (n = 4 per level). To study the production of WBC fragments, 'male' WBCs were spiked into 'female' plasma units to 4 x 10(9) WBCs/l and stored at room temperature prior to filtration (n = 4 per storage time; t = 0, 24 or 48 h). DNA was measured by both albumin real-time PCR and Y real-time PCR. Intact WBCs were counted by using flow cytometry. The number of WBC fragments was calculated by subtracting cell-free DNA (real-time PCR on supernatant) and intact WBCs (flow cytometry) from the total DNA amount (real-time PCR). RESULTS: Spiking of 'male' WBCs into 'female' PCs showed that the Y real-time PCR is linear and has a reproducible quantitative range down to 0.03 WBC/microl, but that the albumin-PCR, in unspiked samples, revealed a total of 6-10 WBC equivalents/microl (eq/microl). After centrifugation, half of this was observed as cell-free DNA in the supernatant, suggesting that the remaining DNA is derived from WBC fragments. The number of intact WBCs, amount of cell-free DNA and number of WBC fragments after filtration increased significantly when filtration was delayed for up to 48 h, from 0.1 WBC/microl, 1.3 WBC eq/microl and 0.6 WBC eq/microl at t = 0 h to 25 WBC/microl, 38 WBC eq/microl and 57 WBC eq/microl at t = 48 h, respectively. CONCLUSIONS: WBC fragments occur in WBC-reduced PCs and increase when products are stored, prior to filtration, up to levels that are equivalent to the amounts of intact WBCs that induce HLA immunization (i.e. > 5 x 10(6)/unit).

Blood Preservation↗
PubMed2004

In vivo PLT increments after transfusions of WBC-reduced PLT concentrates stored for up to 7 days.

BACKGROUND: Bacterial screening and improvement of storage conditions of leukoreduced PLT concentrates (LR-PCs) allows extension of their storage period from 5 to 7 days. STUDY DESIGN AND METHODS: For in vitro studies, 40 LR-PCs made from five buffy coats and plasma were studied for 8 days. For in vivo studies, routinely produced LR-PCs stored for 2 to 7 days after blood collection were administered to clinically stable thrombocytopenic patients. CI1 h was calculated after 353 transfusions (67 patients), and CCI1 h, after 195 transfusions (55 patients), with pretransfusion PLT counts of not greater than 20 x 10(9) per mL. RESULTS: Storage experiments showed that the pH of LR-PCs remained greater than 6.8 for 8 days, provided that the PLT concentration was less than 1.3 x 10(9) per mL. Routinely produced LR-PCs had a volume of 282 +/- 15 mL (n = 10,193) and contained 329 x 10(9)+/- 40 x 10(9) PLTs (n = 3467). For 7-day-old LR-PCs, 76 of 78 (97%) of the transfusions resulted in a CI1 h of at least 10 and 37 of 39 (95%) in a CCI1 h of at least 7.5, which indicated levels for successfulness. Mean +/- SE values of CI1 h and CCI1 h of 7-day-old LR-PCs were 28.7 +/- 2.3 (n = 78) and 19.0 +/- 2.0 (n = 39), respectively. No significant differences were observed between 5- and 7-day-old LR-PCs transfused with respect to CI1 h and CCI1 h values. CONCLUSION: In vitro and in vivo studies showed that LR-PCs can be stored for up to 7 days with excellent clinical results, provided that they are routinely screened for bacterial contamination.

Bacterial Infections↗
PubMed2004

[Antithrombotic therapy and dental surgery with bleeding].

The advantages of stopping or reducing antithrombotic therapy should always be weigh out against the disadvantage of the enlarged risk of thrombo-embolic complications. A review of the available literature showed that, in general, it is not necessary to stop the use of aspirin or clopidogrel in case of normal dental surgery. If in doubt and in all cases of other antithrombotic therapy the medical specialist should be consulted. The treatment of postoperative hemorrhage is described and the medical legal aspects are discussed.

Aspirin↗