Biomedical subjects

F Christiansen

Publications and source records attributed to F Christiansen.

At least 19 recordsLinked to original sources

PubMed2000

Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p < 0.05). Patients whose donors were matched at the beta-block had significantly less severe acute graft versus host disease (p < 0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

Adolescent↗

PubMed1999

[Spiral computed tomography--solution to diagnostic problems in pulmonary embolism?].

Clinical diagnosis of pulmonary embolism is difficult and often dependent on radiological methods. In Sweden scintigraphy has hitherto been the method most commonly used, though all too often it leaves the diagnosis in doubt. Spiral computed tomography, performed during continuous infusion of contrast medium, clearly depicts the pulmonaries arteries, emboli appearing as filling defects. The examination takes less than one minute. Although the method has yet to be fully evaluated, it is already available at most Swedish hospitals. Results presented so far suggest that the technique has great potential, and may become the method of choice in the diagnosis of pulmonary embolism.

Contrast Media↗

PubMed1999

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Bone Marrow Transplantation↗

PubMed1999

Matching for TNF microsatellites is strongly associated with matching for other non-HLA MHC sequences in unrelated bone marrow donor-recipient pairs.

The use of unrelated donors for bone marrow transplantation is associated with an increased morbidity and mortality when compared with HLA identical siblings. We have demonstrated previously that matching of unrelated donors and recipients for TNFa microsatellites is correlated with lower CTLp frequencies. Matching of unrelated donors and recipients for other non-HLA sequences in the major histocompatibility complex has been reported to result in less graft-versus-host disease and improved survival. It has been argued that matching for non-HLA sequences in the MHC in addition to the HLA genes themselves results in matching for the entire MHC and is therefore the equivalent of providing an HLA identical sibling donor. In order to test this hypothesis we have examined TNFa microsatellites of unrelated donor recipient pairs in whom matching for HLA loci, non-HLA sequences near HLA B (beta-block markers) and non-HLA sequences near DRB1 (delta-block markers) had been determined. All 17 patients who were matched for HLA and non-HLA markers were also matched for TNF microsatellites. This data supports the idea that matching for HLA genes and non-HLA markers results in matching at all other loci in the MHC.

Bone Marrow Transplantation↗

PubMed1999

A special report: histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors.

The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. Registry and cord blood bank guidelines suggest that, at a minimum, initial HLA typing should be performed for three HLA loci, HLA-A, -B, and -DR, at low resolution/split antigen level. DNA-based testing methods should be utilized for HLA-DR typing. DNA-based testing for HLA-A and -B should replace serologic testing of new volunteer donors and cord blood units as robust protocols and reagents become available to the laboratories. Transplant center guidelines for typing of patient, family and to confirm the HLA types of potential unrelated donors should include, at the minimum, typing HLA-A, B, and -DR loci using primarily DNA-based testing methods at allele level resolution for DRB1 and low resolution/ split antigen level for HLA-A and -B. It is strongly recommended that the typing of a patient and the selected donor be performed using the same set of reagents, methodology, and interpretation criteria with fresh tissue samples to ensure HLA identity. Guidelines for laboratory accreditation, approaches to quality assurance and quality control for HLA testing, and suggestions for the format of the HLA database of donor types are also outlined.

Hematopoietic Stem Cell Transplantation↗

PubMed1999

Histocompatibility testing guidelines for hematopoietic stem cell transplantation using volunteer donors: report from The World Marrow Donor Association. Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association.

Adult↗

PubMed1999

The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases.

An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the clearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150-200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis to the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.

Animals↗

PubMed1997

Rater agreement at lung scintigraphy after consensus training.

PURPOSE: Using the PIOPED criteria in the interpretation of lung scintigraphy, perfect agreement between experienced raters with training in consensus interpretation has been demonstrated. In a previous paper we found a kappa value of 0.54 (0.45-0.63) between experienced raters with no experience of interpretation in consensus; this is significantly lower than the perfect agreement described between consensus-trained raters. The purpose of this study was to reinvestigate the same study population with the same raters, but this time after they had undergone consensus training. MATERIAL AND METHODS: Lung scintigrams of 192 patients were reviewed and categorized according to the PIOPED criteria by 2 raters after consensus training. The 2 raters reviewed a training material of 59 cases, which was not part of the study population, in order to reach a full consensus interpretation. RESULTS: After consensus training the kappa value was 0.57 (0.48-0.66). Three cases had a discrepancy of 2 categories (1.6%), and the remaining discrepancies were of one category. CONCLUSION: Consensus training did not significantly improve the agreement rate between experienced raters from different hospitals. A substantial improvement in agreement rates between hospitals may make heavy demands on resources.

Humans↗

PubMed1997

Adding a visual linear scale probability to the PIOPED probability of pulmonary embolism.

PURPOSE: Reporting a lung scintigraphy diagnosis as a PIOPED categorical probability of pulmonary embolism offers the clinician a wide range of interpretation. Therefore the purpose of this study was to analyze the impact on lung scintigraphy reporting of adding a visual linear scale (VLS) probability assessment to the ordinary PIOPED categorical probability. MATERIAL AND METHODS: The study material was a re-evaluation of lung scintigrams from a prospective study of 170 patients. All patients had been examined by lung scintigraphy and pulmonary angiography. The scintigrams were re-evaluated by 3 raters, and the probability of pulmonary embolism was estimated by the PIOPED categorization and by a VLS probability. The test was repeated after 6 months. RESULTS: There was no significant difference (p > 0.05) in the area under the ROC curve between the PIOPED categorization and the VLS for any of the 3 raters. Analysis of agreement among raters and for repeatability demonstrated low agreement in the mid-range of probabilities. CONCLUSION: A VLS probability estimate did not significantly improve the overall accuracy of the diagnosis compared to the categorical PIOPED probability assessment alone. From the data of our present study we cannot recommend the addition of a VLS score to the PIOPED categorization.

Angiography↗

PubMed1997

Observer agreement and accuracy for lung scintigraphy: a comparison with pulmonary angiography.

This study investigated whether the moderate observer agreement rate for lung scintigraphy, when using the PIOPED criteria, reflects significant variations in accuracy. In a prospective study, 170 patients were investigated with lung scintigraphy and pulmonary angiography. The lung scintigrams were read according to the PIOPED criteria by three skilled observers from different hospitals who had no experience of consensus interpretation. The scintigrams were reinterpreted 6 months later. The inter-observer agreement rates were moderate and fair, with kappa values of 0.49 (0.44-0.54) for the first reading and 0.36 (0.31-0.41) for the second reading. The intra-observer agreement rates were good and moderate, with kappa values of 0.62 (0.51-0.73), 0.52 (0.42-0.62) and 0.54 (0.44-0.64). There were no significant differences between the observers in the areas under the ROC curves. However, one observer showed a significant difference between his first and second reading (P = 0.02). All three observers showed good accuracy. Although there were substantial variations in the inter- and intra-observer agreement rates, this was only reflected to a minor degree in the accuracy.

Angiography↗

PubMed1997

Diagnostic imaging of acute pulmonary embolism.

The common strategy of combining clinical information, lung scintigraphy and pulmonary angiography in the diagnosis of acute pulmonary embolism (PE), has many limitations in clinical use. The major causes are that pulmonary angiography and lung scintigraphy are not universally available, and that pulmonary angiography is very expensive. The purpose of this thesis was to analyse different aspects of validity in regard to lung scintigraphy, pulmonary angiography, spiral CT, and ultrasound of the legs, with the subsequent intention of discussing new diagnostic strategies. Observer variations in lung scintigraphy interpretation when applying the PIOPED criteria were tested in 2 studies with 2 and 3 observers respectively and expressed as kappa values. The ability to improve agreement in lung scintigraphy interpretation was tested by training 2 observers from different hospitals. The impact of 3 observers' variations in lung scintigraphy interpretation when compared to pulmonary angiography, was tested by comparing the ROC areas of the observers. The value of combining subjectively derived numerical probabilities and the PIOPED categorical probabilities in lung scintigraphy reporting was compared to using the PIOPED categorization only, and this was tested by comparing ROC areas. The sensitivity and specificity of detecting an embolic source in the deep veins of the legs by ultrasound as a sign of PE when lung scintigraphy is inconclusive, was tested by comparison with pulmonary angiography. The sensitivity and specificity of spiral CT, compared to pulmonary angiography, was tested by comparison to pulmonary angiography. The inter- and intra-observer kappa values were in the range of moderate and fair. It was not possible to achieve better kappa values after training. Although observer variations were substantial, the accuracy did not differ significantly between the 3 observers. Incoorporating subjectively derived probabilities into lung scan reporting could not reduce the number of inconclusive investigations. Sensitivity and specificity of ultrasound in detecting PE was 0.70 and 0.97, respectively. However, 2 patients (of 9) had deep venous thrombosis and no pulmonary emboli at angiography. The sensitivity and specificity of spiral CT was 0.90 and 0.96, respectively. The observer variations at lung scintigraphy are substantial and may be difficult to improve between hospitals, even though the accuracy of observers in general is good. Although subjectively derived interpretation criteria did not show to be useful when added to categorical interpretation criteria, they may be useful when substituting established criteria. Despite recent progress in refining interpretation criteria, a substantial fraction of the patients still need pulmonary angiography to be performed. However, in many patients pulmonary angiography is not performed as prescribed. Spiral CT and ultrasound of the legs is a new favourable diagnostic strategy with a high validity in detecting venous thromboembolic disease, and a good availability and cost-effectiveness.

Acute Disease↗

PubMed1996

Ultrasound at scintigraphic "intermediate probability of pulmonary embolism".

For diagnosis of pulmonary embolism (PE), ventilation/perfusion lung scintigraphy is routinely used; approximately one-third of the patients will have the diagnosis "intermediate probability of PE" (inconclusive). In this group only about 33% are found to have pulmonary emboli if examined with pulmonary angiography. To evaluate the diagnostic, therapeutic, and economic consequences of ultrasound of the legs as a complementary diagnostic investigation to "intermediate probability", 72 consecutive patients were investigated with bilateral ultrasound of the proximal deep veins of the legs and pulmonary angiography in a prospective study. Ten patients had PE, of whom 7 had deep venous thrombosis, and 62 had no PE, of whom 2 had deep venous thrombosis. The negative predictive value of ultrasound was 0.95. In view of the importance of adequate treatment and rational use of public health care expenditure, complementary diagnostics should be performed, and ultrasound is an adequate complementary investigation.

Adult↗

PubMed1996

Rater agreement in lung scintigraphy.

PURPOSE: The PIOPED criteria in their original and revised forms are today's standards in the interpretation of ventilation-perfusion scintigraphy. When the PIOPED criteria are used by experienced raters with training in consensus interpretation, the agreement rates have been demonstrated to be excellent. Our purpose was to investigate the rates of agreement between 2 experienced raters from different hospital who had no training in consensus interpretation. MATERIAL AND METHODS: The 2 raters investigated a population of 195 patients. This group included 72 patients from a previous study who had an intermediate probability of pulmonary embolism and who had also been examined by pulmonary angiography. RESULTS: The results demonstrated moderate agreement rates with a kappa value of 0.54 (0.45-0.63 in a 95% confidence interval), which is similar to the kappa value of the PIOPED study but significantly lower than the kappa values of agreement rates among consensus-trained raters. There was a low consistency in the intermediate probability category, with a proportional agreement rate of 0.39 between the experienced raters. CONCLUSION: The moderate agreement rates between raters from different hospitals make it difficult to compare study populations of a certain scintigraphic category in different hospitals. Further investigations are mandatory for accurate diagnosis when the scintigrams are in the category of intermediate probability of pulmonary embolism.

Humans↗

PubMed1995