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Biomedical subjects

W van der Bij

Publications and source records attributed to W van der Bij.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance: a comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome.

BACKGROUND: Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in donor-specific T cell frequencies also occurs after clinical lung transplantation and if such a decrease lowers the risk for bronchiolitis obliterans syndrome (BOS), a hallmark of chronic graft dysfunction. Therefore, we compared changes in posttransplant donor-specific cytotoxic T lymphocyte (CTLp) and helper T lymphocyte precursor (HTLp) frequencies in lung allograft recipients with good graft function and in recipients with BOS. METHODS: Donor and third party specific CTLp and HTLp frequencies were determined by limiting dilution assay in pre- and posttransplant (1 year) peripheral blood samples of lung allograft recipients with good graft function (n = 13) and BOS (n = 10). RESULTS: In recipients with good graft function, mean donor-specific CTLp frequencies decreased after transplantation (183 vs. 16 precursors before and after transplantation, respectively). Additionally, HTLp frequencies decreased but this was not specific for donor alloantigens because third party-specific HTLp frequencies decreased also. Surprisingly, recipients with BOS also showed a decrease in mean donor-specific CTLp frequencies after transplantation (332 vs. 49 precursors before and after transplantation, respectively). Again, HTLp frequencies decreased nonspecifically. CONCLUSIONS: We conclude that donor-specific CTLp frequencies decrease after lung transplantation, but that this does not result in transplantation tolerance protecting the lung against the development of chronic graft dysfunction.

Acute Disease↗
PubMed2000

Creatinine-based estimation of rate of long term renal function loss in lung transplant recipients. Which method is preferable?

BACKGROUND: Progressive renal function loss during long-term follow up is common after lung transplantation and close monitoring is warranted. Since changes in creatinine generation and excretion may occur after lung transplantation, the reliability of creatinine-based methods of renal function assessment to serial measurements of glomerular filtration rate (GFR) were compared in this population. METHODS: Renal function with serial measurements of GFR by iothalamate clearance every 6 months after transplantation was studied in a cohort of 40 lung transplant recipients with at least 24 months of follow up, transplanted between November 1990 and October 1995 in this center. The correlation between the rate of renal function loss calculated from the slope of GFR and the following creatinine-based indices: 1/S-creatinine, Cockcroft clearance and Levey estimation were analyzed. The absolute difference between GFR and Cockcroft clearance and Levey estimation pre- post-transplantation at several points was also studied. RESULTS: The slopes of 1/S-creatinine (r = 0.85), Cockcroft clearance (r = 0.86), and the Levey estimation (r = 0.84) correlated significantly with the slope of GFR as measured by iothalamate clearance. However, all creatinine-based slopes underestimate the rate of GFR loss. Cockcroft clearance and the reciprocal value of serum creatinine do not detect small GFR losses. During long-term follow up a time-dependent discrepancy between Cockcroft clearance, Levey estimation and GFR was observed which may partially explain the observations for this population. CONCLUSION: Creatinine-based slopes correlate with GFR slopes after lung transplantation, but consistently underestimate the rate of GFR decline. The Levey estimation is the most sensitive method used to detect small GFR losses and may be preferable when no GFR measurement is available. In special conditions when an accurate renal function assessment is needed true GFR may be necessary.

Adult↗
PubMed2000

Visual symptoms after lung transplantation: a case of progressive multifocal leukoencephalopathy.

After solid organ transplantation, signs and symptoms of the central nervous system may present a diagnostic challenge. A 43-year-old patient developed a decrease in vision 15 months after bilateral lung transplantation. The initial diagnosis was a left posterior cataract, but left eye cataract extraction did not improve his vision. Seizures led to investigation of a broader differential diagnosis (cyclosporine intoxication, post-transplant lymphoproliferative disorder, infectious disease, chronic lymphatic leukemia). The clinical diagnosis of progressive multifocal leukoencephalopathy (PML) was confirmed by demonstration of JC virus in the cerebrospinal fluid and by autopsy findings. Modulation of the immunosuppressive regimen was unsuccessful. This case illustrates that decreased vision in immunocompromised patients may be the first manifestation of PML.

Adult↗
PubMed2000

Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation.

In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.

Adult↗
PubMed2000

Bronchiolitis obliterans syndrome and additional costs of lung transplantation.

STUDY OBJECTIVES: The influence of bronchiolitis obliterans syndrome (BOS) on costs after lung transplantation was investigated by comparing the costs of patients with and without this condition. DESIGN: Follow-up costs were prospectively investigated in a medical technology assessment of the Dutch Lung Transplant Program, in relation to the development of the BOS. First, average follow-up costs per week per patient were compared between patients who did or did not develop BOS. Second, in the BOS group, these costs were compared before and after the onset of BOS. SETTING: Dutch Lung Transplant Program, University Hospital of Groningen. RESULTS: Data on 53 patients (37 patients without BOS and 16 with BOS) who underwent transplantation between November 1990 and April 1995 were available. The average follow-up time of these 53 patients was 1.5 years. The follow-up costs amounted to an average (in Dutch guilders [Dfl]) of 1,774/wk for non-BOS patients, compared to 3,072/wk for BOS patients (+ 73%; p = 0.002; one Dfl = 50 cents US currency). This difference in costs was largely accounted for by an increase in used health-care resources, in particular hospitalization and medication. For the BOS patients, the average costs per week before and after the onset of BOS were 1,941 Dfl and 2,422 Dfl, respectively. CONCLUSION: BOS is associated with substantial extra costs. These findings reemphasize the need to focus efforts on prevention of BOS to enhance the cost-effectiveness of lung transplantation.

Adult↗
PubMed2000

Vaginal delivery after lung transplantation.

Lung transplantation is accepted as an effective treatment for patients with end-stage pulmonary disease. With gaining experience worldwide and more favorable outcomes after lung transplantation, increasing numbers of pregnancies among lung transplant recipients are expected to occur. Most of the knowledge on the outcome of pregnancies in women with organ allografts is obtained from kidney recipients. However, in the literature few reports exist to support and guide obstetric management regarding outcome of pregnancy and mode of delivery after a preceding lung transplantation (1-4). To our knowledge, we describe the first case of successful spontaneous vaginal delivery near term after a single lung transplantation.

Adult↗
PubMed1999

[Survival and impact of bronchiolitis obliterans syndrome after lung transplantation at the Academic Hospital Groningen, 1990/'98].

OBJECTIVE: To describe the results of the lung transplantation programme in Groningen in relation to the bronchiolitis obliterans syndrome (BOS), in the first 118 consecutive patients. DESIGN: Retrospective. METHOD: Data were collected on the 118 patients subjected to lung transplantation in November 1990 to June 1998 in the University Hospital Groningen, the Netherlands, regarding the prevalence of chronic transplant dysfunction (BOS) and survival. RESULTS: 117 lung transplantations (95 bilateral lung transplantations including 2 retransplants, and 22 single lung transplantations) and 1 heart-lung transplantation had been performed. The patients were 70 males and 48 females with a mean age of 42 years (range: 9-64). The mean (SD) survival at 1, 2, 3 and 5 years post transplantation was 83% (3), 70% (4), 66% (5) and 61% (5) respectively. The median survival amounted to 2447 days. The mean (SD) prevalence of BOS at respectively 1, 2, 3 and 5 years post transplantation was 32% (5), 36% (5), 44% (5) en 54% (6). After a diagnosis of BOS stage I the median survival was 649 days. CONCLUSION: The survival of the lung transplant programme of the University Hospital Groningen is considered to compare favourably with other centres. The prevalence of BOS is considerable, and comparable with the prevalence of BOS reported by other programmes. BOS is associated with a decreased life expectancy.

Academic Medical Centers↗
PubMed1999

Comparison of the Murex Hybrid Capture CMV DNA (v2.0) assay and the pp65 CMV antigenemia test for the detection and quantitation of CMV in blood samples from immunocompromised patients.

BACKGROUND: Presently the semiquantitative pp65 cytomegalovirus (CMV) antigenemia test on white blood cells is often used for monitoring transplant patients for the appearance of active CMV infections. However, the need for immediate processing of the specimens and the lack of interlaboratory standardization of the test may sometimes be a disadvantage. OBJECTIVE: The aim of this study was to investigate the value of the recently developed second version of the Murex Hybrid Capture (MHC) CMV-DNA assay (v 2.0) in comparison with the CMV-pp65 test. The MHC CMV-DNA assay is a quantitative solution hybridization antibody capture assay, using alkaline phosphatase conjugated antibodies and a chemiluminescent substrate. STUDY DESIGN: 248 EDTA blood samples from 33 renal transplant patients and 32 samples from 22 other immunocompromised patients were tested by both the MHC CMV-DNA assay and the CMV-pp65 test. RESULTS: The qualitative ( + or -) results of both tests showed an overall concordance of 81.4%. Calculations on the basis of discordancy analyses showed that the sensitivity, the specificity, and the positive and negative predictive values were 87.7, 98.3, 98.6, 85.2% for the MHC CMV-DNA assay and 76.6, 100, 100, 75.5% for the CMV-pp65 test. Comparison of the quantitative results of both tests systems showed a correlation coefficient of 0.837. In addition, retesting of 50 samples with the MHC-CMV-DNA assay showed an excellent reproducibility with a correlation coefficient of 0.992. All patients which were tested regularly (at least five samples) became either positive with both tests or with none of them. Neither test system detected CMV significantly earlier than the other one. Both tests became strongly positive in all transplant patients with symptomatic CMV infections, and both tests showed a rapid decline of CMV during subsequent antiviral treatment. CONCLUSION: The quantitative Murex Hybrid Capture CMV-DNA assay (v 2.0) may become a valuable additional tool in CMV diagnosis. Further studies will be needed to support this preliminary judgement.

AIDS-Related Opportunistic Infections↗
PubMed1998

Quantitation of immunosuppression by flow cytometric measurement of the capacity of T cells for interleukin-2 production.

BACKGROUND: Methods to quantitate the effects of immunosuppressive drugs on immune reactivity might be helpful for monitoring immunosuppressive treatment. Cyclosporine (CsA) inhibits the induction of cytokine synthesis in T cells, and measurement of interleukin (IL)-2 production might constitute a parameter of this drug's effect. METHODS: We determined the percentages of CD4+ and CD8+ lymphocytes producing IL-2 upon stimulation by phorbol myristate acetate and calcium ionophore in whole blood culture, using immunostaining of intracytoplasmatic and membrane markers, followed by multiparameter flow cytometry. A total of 38 clinically stable transplant patients on various immunosuppressive protocols were studied. RESULTS: The percentage of CD4+ T cells producing IL-2 was strongly reduced in patients compared with healthy controls (23% [range, 3-68%] vs. 59.0% [range, 41-70%]; P=0.000035). The percentage of CD4+ T cells producing IL-2 was negatively correlated with the CsA level (Rc=-0.0821, P=0.00002297) but not with prednisolone or azathioprine doses. Fewer CD8+ T cells produced IL-2 in transplant patients compared with controls, but the difference failed to reach statistical significance. The percentage of CD8+ T cells capable of producing IL-2 was inversely correlated to CsA levels (Rc=-0.0375, P=0.0011). CONCLUSIONS: These data suggest that the functional effects of CsA in transplant recipients can be quantitatively determined and that the capacity of CD4+ T cells to produce IL-2 upon stimulation constitutes a functional parameter of CsA effects on the immune system. Prospective studies are required to determine whether this method is useful for clinical monitoring.

Adult↗
PubMed1998

[The evaluation of the lung transplantation program at Groningen: survival rate, quality of life, and cost-effectiveness].

OBJECTIVE: Assessment of the effectiveness and cost-effectiveness of lung transplantation, and the supply and need of donor lungs in the Netherlands. DESIGN: Prospective and comparative. SETTING: University Hospital Groningen, the Netherlands. METHOD: Costs and effects were compared of the situations with and without a lung transplantation programme. Costs and effects were registered during all phases of this programme (November 1990 to February 1996; 76 patients reached the transplantation phase), and the situation without a programme was judged on pre-transplant evidence. The effect of lung transplantation on survival was assessed by means of a Cox regression model, and in the quality of life study of a longitudinal analysis was applied. The supply and the need of donor lungs were based on several registrations. RESULTS: Lung transplantation led to a significant improvement in survival and quality of life. The average gain in life years and quality adjusted life years (Qalys) were estimated at 4.4 and 5.2, respectively. The average costs per transplanted patient were estimated at Hfl. 670,000 (Hfl. 1 is about 0.5 dollar). The average costs per life year and Qaly gained were estimated at Hfl 153,000 and Hfl. 120,000 (both discounted), respectively. The annual need of donor lungs was estimated at 50-75, the annual supply at 17-27. CONCLUSIONS: Lung transplantation leads to improvement of survival and quality of life. However, it involves considerable costs and the cost-effectiveness is unfavourable compared with other Dutch transplant programmes. Moreover, there is a great discrepancy between the need and supply of donor lungs in the Netherlands.

Adult↗
PubMed1998

Quantification of immunosuppression by flow cytometric measurement of intracellular cytokine synthesis.

The availability of a method to measure the effects of drugs on immune reactivity should be helpful in optimizing treatment after organ transplantation. Since cyclosporine A (CSA) interferes with activation of T cells and cytokine synthesis, production of IL-2 and IFN-gamma might constitute a marker of this drug's effects. We measured the capacity for mitogen-stimulated production of these cytokines in whole blood by using immunostaining of intracellular and membrane antigens, followed by flow cytometry. The percentage of CD4+ T cells producing IL-2 or IFN-gamma was strongly reduced in 20 transplant patients compared with 24 healthy controls. The capacity for IL-2 production of CD4+ and CD8+ cells correlated inversely with CSA blood levels (P values 0.0087 and 0.0396, respectively). IFN-gamma production by CD4+ T cells showed a negative correlation with the prednisolone dose (P = 0.0175) and, for the CD8+ subset, with CSA trough levels (P = 0.0023). These data show that inhibition of T cell cytokine synthesis by CSA and prednisolone can be quantified.

Flow Cytometry↗
PubMed1998

Technology assessment of the Dutch Lung Transplantation Program.

The costs, effects, and cost-effectiveness of the Dutch Lung Transplantation program were assessed. The results show that lung transplantation is a very costly intervention that improves survival and quality of life. Costs per life-year and per QALY gained were, respectively, US $90,000 and US $71,000.

Algorithms↗
PubMed1998

Haemophilus influenzae in lung explants of patients with end-stage pulmonary disease.

In order to determine the presence and distribution of Haemophilus influenzae in lung tissue sections, we obtained lung explants from 49 lung transplant recipients with cystic fibrosis (CF) (n = 16), chronic obstructive pulmonary disease (COPD) including emphysema (n = 16), bronchiectasis (n = 5), pulmonary hypertension (n = 9), Langerhans cell histiocytosis (n = 1), and idiopathic pulmonary fibrosis (n = 2). Analysis was done by selective culturing, immunoperoxidase (IP) staining, and by polymerase chain reaction (PCR). H. influenzae was cultured from specimens of the lung explants from one CF and one COPD patient. IP staining of tissue sections was positive in 24 patients (10 CF patients, eight COPD patients, two bronchiectasis patients, and four patients with noninfectious pulmonary diseases). IP-positive tissue sections were PCR-positive, and IP-negative sections were PCR-negative. H. influenzae was more frequently detected in tissue sections of lung explants from CF and COPD patients than from patients with bronchiectasis or noninfectious pulmonary diseases. H. influenzae was diffusely present in the epithelium, the submucosa of the bronchi, the bronchioles, the interstitium, and the alveolar epithelium. H. influenzae was localized extracellularly alone and in bacterial clusters, and was also associated with macrophages in CF patients. The results of this study demonstrate that H. influenzae is often present in the lungs of patients with end-stage pulmonary disease, especially CF and COPD patients. H. influenzae is diffusely present in the respiratory epithelium and subepithelial layers of the lungs of these patients.

Adolescent↗
PubMed1998

Cost-effectiveness of lung transplantation in The Netherlands: a scenario analysis.

STUDY OBJECTIVES: To calculate cost-effectiveness of scenarios concerning lung transplantation in The Netherlands. DESIGN: Microsimulation model predicting survival, quality of life, and costs with and without transplantation program, based on data of the Dutch lung transplantation program of 1990 to 1995. SETTING: Netherlands, University Hospital Groningen. PATIENTS: Included were 425 patients referred for lung transplantation, of whom 57 underwent transplantation. INTERVENTION: Lung transplantation. RESULTS: For the baseline scenario, the costs per life-year gained are G 194,000 (G=Netherlands guilders) and the costs per quality-adjusted life-year (QALY) gained are G 167,000. Restricting patient inflow ("policy scenario") lowers the costs per life-year gained: G 172,000 (costs per QALY gained: G 144,000). The supply of more donor lungs could reduce the costs per life-year gained to G 159,000 (G 135,000 per QALY gained; G1 =US $0.6, based on exchange rate at the time of the study). CONCLUSIONS: Lung transplantation is an expensive but effective intervention: survival and quality of life improve substantially after transplantation. The costs per life-year gained are relatively high, compared with other interventions and other types of transplantation. Restricting the patient inflow and/or raising donor supply improves cost-effectiveness to some degree. Limiting the extent of inpatient screening or lower future costs of immunosuppressives may slightly improve the cost-effectiveness of the program.

Cost-Benefit Analysis↗