Evaluation of the fluorescein test in the diagnosis of incompetent perforating veins.
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Adult↗
Biomedical subjects
M Thomsen
Publications and source records attributed to M Thomsen.
Typing for human alloantigens with the primed lymphocyte typing technique.
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Animals↗
Frequency of nine HLA-D antigens in the Danish population.
The frequency of HLA-Dw1-8 and DH was determined in 389 unrelated healthy Danes and in 257 kidney patients. All individuals were HLA-A, B, C typed, 168 of the normal individuals and all kidney patients were typed for HLA-DR. The frequency of Dw1-8 in the normal material and kidney patient material was quite similar except for Dw6, which showed an increased frequency among the kidney patients, but as the patients are not prospectively ascertained, the significance of this finding is unclear. The frequency of the blank allele is 0.19 which is comparable to other Scandinavian materials but much lower than that seen in the joint report of the 8th International Histocompatibility Workshop. The D frequencies correlate quite well with the HLA-DR frequencies, the biggest discrepancy between D and DR exists for D/DR4, where DR4 is much "broader". The DR4 positives can be divided into the Dw4 positives, strongly associated with B15 and the Dw4 negatives, not associated with B15 but with B40. Primed lymphocyte typing in some cases followed HLA-DR, in other cases HLA-D assignment. For HLA-D/DR2 the DR assignment also seemed to be broader, the DR2 positive, Dw2 negative group not being associated with B7, but possibly with B5. In the assignment of HLA-D determinants, "false negatives" have caused problems in many materials, but the inclusion of a number of known control responders in our experiments has made it possible to increase the accuracy of assignment by adjusting the cut-off level for typing responses according to the typings of the controls.
Denmark↗
Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles.
The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.
Adenylyl Cyclases↗
HLA and heterogeneity of multiple sclerosis.
Age at onset, debut symptoms, optic nerve signs, and severity of symptoms were evaluated from the medical records of 135 patients with MS. HLA-D/DR2 was significantly more frequent in rapidly progressive MS, and D/DR2 seemed to confer both susceptibility to the disease and to more rapid progression. However, D/DR3 seemed to protect against rapid progression.
Adult↗
HLA and diabetes.
HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.
Diabetes Mellitus↗
Occurrence of lateral incompetent perforating veins of the calf. Usefulness of the posterior midline incision.
This investigation is an evaluation of the posterior approach for subfascial ligation of incompetent perforating veins (IPV) of the calf. The distribution of veins found incompetent at operation and the incidence of wound complications were studied. 39 patients with clinical multiple perforating vein insufficiency were operated on. At the end of the operation the crural fascia was sutured in half of them. The tissue pressure in the gastrocnemius muscle was measured in 13 patients postoperatively. 151 IPVs were found in the 39 legs operated on (3.8/ leg). 25% were found on the lateral side, and were inaccessible from a medial incision. Postoperative infection was noted in 3 patients and in a further 6 mostly minor skin necrosis with delayed healing occurred. The incidence of delayed healing was not influenced by fascia suture and the tissue pressure was normal in the 13 patients so examined. The posterior incision gives excellent access to both medial and lateral IPVs and makes possible resection of the short saphenous vein at the same time. This approach is useful when ulcers and stasis dermatitis are present on both medial and lateral sides or when there are medial IPVs and signs of incompetence of the short saphenous vein.
Adult↗
HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus.
Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.
Diabetes Mellitus↗
Typing for human alloantigens with the primed lymphocyte typing (PLT) technique with notes on the interpretation of PLT data.
A typing system for HLA-D/DR-associated PLT-defined determinants, which have been called "DP" antigens, is reported. Some of the results concerning a data interpretation system, the reproducibility of PLT results, and the correlations between the results of HLA-D, -DR, and DP typing are presented. Also, a "new" human alloantigen, EP1, not belonging to the series of DP antigens, is defined with PLT.
Epitopes↗
Association of pernicious anemia and intrinsic factor antibody with HLA-D.
One-hundred-and-six patients with pernicious anemia were HLA-A, B, C typed by serological technique and HLA-D typed by mixed lymphocyte culture technique for the specificities HLA-Dw1 - 8 and the locally defined D "H". In 13 cases, the D-typing was unsuccessful due to technical difficulties. HLA-A, B, C antigen frequencies did not show any significant deviation from expected values, while D typing showed increased frequencies of Dw2 and Dw5 and a possibly decreased frequency of Dw3. The typing was compared with clinical data such as the presence of organ specific autoimmune disease in first degree relatives, presence of anemia or myelopathy at time of diagnosis and presence of antibodies towards parietal cells or intrinsic factor. The presence of intrinsic factor antibody was associated with the presence of Dw2 and a decrease of Dw5 and possibly also with a decrease of Dw4. No associations were found for the other investigated parameters. If intrinsic factor antibodies have a pathogenetic role, our findings might reflect a heterogeneity of pernicious anemia. These findings and the recently reported association between HLA-DR5 and Hashimoto's disease link these two thyrogastric diseases together to form a special subgroup within the group of organspecific autoimmune diseases; the other diseases in the group have as a common denominator the frequent presence of D/DR3.
Anemia, Pernicious↗
Technical aspects of the primed lymphocyte typing (PLT) technique.
The influence of different culture conditions in the primary and secondary cultures of the primed lymphocyte typing (PLT) technique was investigated with special reference to the discriminatory capacity of the PLT-cells generated. In the primary cultures, the maximal yield of PLT-cells was observed early (about day 7) and decreased thereafter, while the maximal specificity was obtained considerably later (about day 14). In the secondary cultures, the optimal culture time was in the interval 42 h - 72 h, and up to this culture length, gamma-irradiation (2,200-8,800 rad) of the secondary stimulators had no effect on the 14C-thymidine uptake of the cultures. In U-form microtiterplates, the number of PLT-cells per well should not be less than 2.5 X 10(4), and higher PLT-cell numbers (e.g. 5.0 X 10(4) per well) may confer further robustness upon the technique. The PLT-cell response and the discrimination was only slightly influenced by the number of secondary stimulator cells in the interval 5 X 10(4) to 2 X 10(5) cells per well. Freezing of the PLT-cells under controlled conditions resulted in a minor loss of viable eosin-excluding cells, while the specificity of the PLT-cells was unaffected. Even when the culture conditions are standardized, it is necessary to perform a normalization of the data in order to obtain reproducible results. The normalization procedure should include a compensation for the variation in (i) the general responding capacity of each PLT-cell and in (ii) the general stimulatory capacity of each secondary stimulator.
Cells, Cultured↗
Correlation between HLA-D/DR associated primed lymphocyte typing (PLT) defined DP-antigens, HLA-D and HLA-DR antigens.
A panel of 79 individuals were typed for HLA-D/DR associated Primed Lymphocyte Typing (PLT) defined "DP"-antigens, HLA-D and HLA-DR antigens. Typing for DP-antigens was carried out with local PLT-cells. HLA-D and -DR typing was performed with all homozygous typing cells and all DR-antisera included in the 8th International Histocompatibility Workshop. Assignments of DP-, HLA-D- and HLA-DR-antigens were done independently and the correlations between DP/D/DR1-8 were analyzed. The panel included random unrelated individuals, and individuals previously found to have one or no identifiable HLA-D antigen (B). In the random group, 80% of the individuals were assigned to possess the same antigen with the 3 techniques, while this was only the case in 46% of B-group individuals. The overall correlation coefficients, r, for the antigens HLA-Dw/-DR/DP1-8 were 0.95 (DP/D), 0.94 (DP/DR), and 0.89 (D/DR). There is a remarkably strong correlation between HLA-D and -DR typing results concerning D/DR1-8, in particular in random individuals. It is possible to select PLT-cells that give typing results which are almost identical to those of HLA-D and -DR typing. When discrepant results were seen, HLA-DR was in general "broader" than DP which in turn was broader than HLA-D, indicating that it may be possible to split HLA-DR/DP1-8 into more "narrow" specificities.
Blood Grouping and Crossmatching↗
HLA-A, B, C, D, DR antigens and primed lymphocyte typing (PLT) defined DP-antigens in juvenile chronic arthritis.
A total of 48 patients with juvenile chronic arthritis (JCA) were typed for HLA-A, -B, -C, -D and -DR antigens and 36 patients were also typed for HLA-D/DR associated "DR"-antigens with the primed lymphocyte typing technique. In the total group of patients, we found increased frequencies of HLA-B27, HLA-Dw/DP5 and HLA-Dw/DP8, and decreased frequencies of HLA-Dw/-DR/DP2. The increased frequencies of HLA-Dw/DP8 and the decreased frequencies of HLA-Dw/-DR/DP2 were primarily found among patients with persistent pauciarticular arthritis. The frequencies of HLA-Dw/-DR/DP4 were increased in patients with polyarticular arthritis. The frequencies of HLA-B27 and -Dw/DP5 were increased in both pauciarticular and polyarticular arthritis. The results indicate (i) that genetic factors controlled by HLA confer susceptibility and/or resistance to JCA, and (ii) that the clinical subdivision of JCA into pauciarticular and polyarticular JCA can be supported by the presence of different genetic markers (HLA-antigens) in the two groups of JCA-patients. If these data can be confirmed HLA-D, -DR or DP typing may be of value in the prognostic evaluation of patients with pauciarticular onset JCA.
Antigens, Surface↗
HLA-DR phenotype and HLA-B,DR haplotype frequencies in 704 unrelated Danes.
HLA-ABC and DR antigens were studied in 704 unrelated Danes (84 cadaver kidney donors, 307 healthy individuals, and 313 uremic patients), HLA-DR1, 2, 3, 4, 7, w8, and w10 were investigated in all individuals, whereas DR5, "DRw6", and w9 were only studied in parts of the material. The frequencies of DR1, 2, 3, 4, 5, and w10 were similar in the three groups, while those of "DRw6", DR7 and w8 differed significantly. The deviation of the DR7 frequency was small and probably due to change; "DRw6" is considered difficult to define, and DRw8 may have been difficult to define in the early part of the material. DR-phenotype distributions showed perfect fits to Hardy-Weinberg expectations for the three groups separately and for the combined group. When our combined DR antigen frequencies were compared with those from another Danish sample (Madsen et al, 1981), significant differences were found for "DRw6", w8 and w10. However, in general, the same HLA-B,DR phenotype combinations showed significant positive associations in the two samples, and most of the corresponding haplotype frequencies and delta values were quite similar.
Denmark↗
HLA-B, -DR haplotype frequencies and gametic association in 1,204 unrelated Danes.
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Denmark↗
The prognostic value of blood-flow measurements during construction of arteriovenous fistulae.
The most common route of access in haemodialysis is the conventional radio-cephalic fistula at the wrist. Some patients are better suited for a graft procedure, however. In order to select the most appropriate approach preoperative assessment of the veins is important. Certain observations made at operation may also be helpful. We have measured the vessel sizes and estimated blood flow before and after establishment of the fistula. 36 radio-cephalic fistulae were made in a series of patients not selected with regard to the condition of the veins, in order to find characteristics indicating a poor prognosis for the fistula. There were 8 early failures (22%), and another fistula ceased to function within 6 months. We found that a fistula flow of less than 40 ml/min immediately after construction was associated with a 70% risk of early failure, and no fistulae with such a flow rate survived 6 months. Neither vessel diameters nor preoperative blood flow in the radial artery influenced the risk of early failure.
Adult↗
HLA-D antigen frequencies in Sjögren's syndrome. Differences between the primary and secondary form.
HLA-A, B, C and D typing was performed in 19 patients with primary Sjögren's syndrome (primary SS) and in 15 patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (RA-SS). In the primary SS group, the frequency of HLA-Dw2 was increased (p less than 0.01; "corrected" p greater than 0.05) while the frequency of Dw3 was non-significantly increased. In the RA-SS patients, the frequency of HLA-Dw4 was increased to 84.6% (relative risk = 22.8; p less than 0.001) and the frequency of Dw2 was non-significantly decreased. An increased frequency of Dw2 in primary SS has not been reported before. To investigate if this observation was due to chance, a new series of 16 patients with primary SS were HLA typed. In this new group, the frequencies of both Dw2 and Dw3 were significantly increased, while the frequency of Dw4 was significantly decreased. In the whole group of primary SS patients, the frequencies of Dw2 were 56.3% (relative risk = 3.7; p less than 0.001). Dw3:50.0% (relative risk = 2.8; p less than 0.01) and Dw4: 6.3% (relative risk = 0.28; p less than 0.05). We conclude that genetic factors associated with the HLA-system are involved in the development of Sjögren's syndrome and that these genetic factors are different in primary and secondary Sjögren's syndrome. In primary Sjögren's syndrome, the association with both Dw2 and Dw3 might suggest a further heterogeneity of the syndrome.
Arthritis, Rheumatoid↗
HLA-DR typing in cadaver kidney donors and recipients in Copenhagen.
Among 224 cadaver kidney transplantations performed since Spring 1977, successful DR typing of both donor and recipient could be done in 149 cases. Assessment of DR match grade and clinical data was done independently. The minimum observation time was 3 months and the time of follow up was 1 December, 1980. There was an effect of DR matching which became significant when only 1. transplants were considered and high risk recipients (i.e. diabetics) excluded. Transfusions were of minor importance on graft survival and the difference was only obvious in the first year after transplantation. Matching for HLA-A, B antigen had no obvious effect on graft survival in this material.
Blood Transfusion↗