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Biomedical subjects

D Nyman

Publications and source records attributed to D Nyman.

At least 19 recordsLinked to original sources

Analysis of Borrelia burgdorferi IgG antibodies with a combination of IgG ELISA and VlsE C6 peptide ELISA.

Enzyme-linked immunosorbent assays (ELISAs) were used to detect antibodies to the C6 peptide of the Borrelia burgdorferi VlsE protein and a selection of B. burgdorferi IgG antigens, separately and as a combination, in 355 serum specimens from blood donors and patients. Western immunoblotting was used as the reference method. The sensitivity of the combined analysis of IgG antigen and C6 peptide analysis was markedly superior to those of the separate analyses. When the C6 peptide and IgG results were concordant, the customary confirmatory Western immunoblotting assay could be omitted, thus reducing the time and cost of analysis.

Antibodies, Bacterial↗

Evaluation of treatment responses in late Lyme borreliosis on the basis of antibody decrease during the follow-up period.

The purpose of this study was to identify a serological marker of successful treatment as distinct from treatment failure in late Lyme borreliosis. Consecutive serum samples from 68 treated patients with late Lyme borreliosis were analyzed during a 1-2 year follow-up period after the start of treatment. End-point enzyme immunoassay titres of IgG1, IgG2, IgG3, and combined IgG1+3 subclasses against a sonicate antigen of Borrelia burgdorferi were determined and compared to the IgG antibody response against Borrelia burgdorferi flagella. Individual half-lives of the antibody levels were calculated for each patient. The half-life values were compared to the patients' clinical outcome in order to find a serological marker of remaining disease activity or relapse. The levels of combined IgG1+3 subclass antibodies against the sonicate antigen and the individual levels of IgG1, IgG2, and IgG3 antibodies did not change significantly after treatment. In contrast, antibodies to flagella decreased markedly after successful treatment, with a half-life of 112+/-92 days (arithmetic mean value +/- SD). This was significantly shorter than the half-life after unsuccessful treatment (271+/-151 days), (P<0.0001). The decrease was observed mainly in IgG1 and IgG4 responses to flagella, less so for IgG2 or IgG3. The results suggest that a rapid decrease in flagella antibodies can serve as a marker for a successful treatment of Lyme borreliosis.

Animals↗

IgG seroprevalence of Lyme borreliosis in the population of the Aland Islands in Finland.

This is a study of people living in Aland, a group of islands in the Baltic Sea between Finland and Sweden. 500 blood donors and 3,248 health service clients who did not have Lyme borreliosis were examined for Borrelia burgdorferi IgG antibodies. The method used was an ELISA containing a selection of diagnostic antigens to a Borrelia burgdorferi PKo strain. It was found that the distribution according to sex, age and titre values was identical in the 2 groups, which were therefore treated as one. 19.7% of all the sera was positive. The prevalence in men was 23.6%, and in women 16.7%. The prevalence rises with age, the highest prevalence being seen in men (44.7%) and women (37.0%) over 70 y of age. The data show that the Aland islands are strongly endemic for Lyme borreliosis compared with international levels of infection.

Antibodies, Bacterial↗

Treatment of late Lyme borreliosis.

The aim of this study was to develop a treatment for late Lyme borreliosis and to compare the clinical results with serological findings before and after treatment. It was done in the Aland Islands (population 25,000), a region endemic for Lyme borreliosis. The patients were the first consecutive 100 patients from the Aland Islands with late Lyme borreliosis. They were followed for at least 1 year after treatment. The clinical results of treatment were compared with results of analyses of flagellar IgG antibodies to Borrelia burgdorferi done at the time of diagnosis before treatment and up to 12 months afterwards. Short periods of treatment were not generally effective. The outcome was successful in four of 13 treatments with 14 days of intravenous ceftriaxone alone, in 50 of 56 assessable treatments with ceftriaxone followed by 100 days of amoxycillin plus probenecid, and in 19 of 23 completed treatments with ceftriaxone followed by 100 days of cephadroxil. Titres of IgG antibodies to B. burgdorferi flagella declined significantly after 6 and 12 months in the patients who had successful treatments. All patients whose final titres were less than 30% of the initial titre were in the successful group. Their titres usually remained above the upper limit of normal for a long time but a decline to a value of less than 30% of that before treatment was always a sign of cure.

Anti-Bacterial Agents↗

Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region.

Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughout a population's history. As a result, disequilibrium mapping may be useful in genomic regions of < 1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, we have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotyped for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (rm = -.76; P < .05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres.

Alleles↗

Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.

Patients with von Willebrand disease in four families in the Aland Islands, including the original family that was described in 1926 by the Finnish physician von Willebrand, were screened for mutations in the Swedish "hot-spot" regions (exons 18, 28, 32, 43, and 45) of the von Willebrand factor gene. One cytosine deletion in exon 18 was detected in each of these families. Linkage analysis and genealogical studies suggest that the deletion present in these four families probably has an origin in common with the mutations in the Swedish patients. Apart from the deletion in exon 18, two close transitions (G-->A at S1263 and C-->T at P1266) in exon 28 on the same chromosome were identified in one individual who married into the original family and in his two children. The transitions could be due to a recombination between the von Willebrand factor gene and its pseudogene.

Adult↗

Late Lyme borreliosis: epidemiology, diagnosis and clinical features.

Lyme borreliosis is endemic in the Aland Islands. Exposure of the inhabitants to bites of the tick Ixodes ricinus is heavy. The purpose of this study was to describe symptoms and signs of patients with late Lyme borreliosis in this area, and to correlate the findings with the epidemiological setting. The first 100 consecutive patients with late Lyme borreliosis found in the region since 1984 are included in this study. Neurological, articular and muscular symptoms and signs dominate. General screening for Lyme disease is not recommended in the area due to uncertainty about how to deal with seropositive healthy persons in this heavily exposed population. The recognition and prompt treatment of erythema migrans and other manifestations of primary Lyme borreliosis is important in order to avoid the late stages of the disease. Treatment of all those suffering tick-bites with an antibiotic would be an option in view of the incidence of infected ticks, but cannot be considered because tick-bites are extremely common among the inhabitants. The region would be suitable for general immunization against Borrelia burgdorferi if the means for doing this becomes available in the future.

Adolescent↗

A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh.

Fibrinolytic treatment of acute deep vein thrombosis (DVT) of the leg with high-dose streptokinase (SK) (100,000 U/h) in 39 cases, or low-dose SK (approx 10,000 U/h) in combination with low-dose heparin in 41 cases, was studied in a prospective randomized trial. The degree of thrombolysis was similar in both groups and did not correlate with age or size of the thrombus or with fibrinogen level. The degree of late recanalization was also similar in both groups. There were however significantly more patients with postthrombotic changes in the low-dose group than in the high-dose group after a mean follow-up time of 31 and 38 months respectively. In the low-dose group 2 intracranial hemorrhages occurred (one was fatal) and one patient died of pulmonary embolism, but there were significantly less allergic side effects to SK. There were no cases of such serious side effects in the highdose group. Although low-dose SK has equal thrombolytic effect it seems inferior to high-dose SK, since it probably causes more severe hemorrhagic side-effects.

Clinical Trials as Topic↗

25 year follow-up of the Aland thyroid study of 1956. Thyroid status and incidence of rheumatoid arthritis.

In 1956, a study of the iodine metabolism in endemic goitre was made on a group of inhabitants of the Aland Islands, an autonomous province of Finland. The number of Alanders studied was 130. In a follow-up study 25 years later, 101 still living subjects from the original study could be traced. 17 of them had become hyperthyroid, 7 had been operated on for non-toxic goitre, and 4 had become hypothyroid. There was no correlation between thyroid hormone excretion values in 1956 and subsequent hyperthyroidism. Rheumatoid arthritis was overrepresented in the goitre group compared with the group without goitres, as well as compared with statistical figures on the frequency of rheumatic disease among the population in general of Aland and of Finland as a whole.

Adolescent↗

Recent investigations of the first bleeder family in Aland (Finland) described by von Willebrand.

The still living members of the original bleeder family on the Aland Islands described by von Willebrand in 1926 have been reinvestigated by using modern laboratory techniques for the measurement of the Factor VIII complex and with regard to platelet aggregation. The low level of F VIII : C activity demonstrated in 1957 could be confirmed in some of the family members, who however all had only mild bleeding symptoms. More consistently, in 6 out of 10, a low F VIIIR : Ag was found; all of those also had a low F VIII : RCoF. In none of the members were excessively low values for any of the parameters found. However, the spectrum of the whole F VIII complex indicates that the original family described by von Willebrand belongs to von Willebrand's disease, type I.

Adolescent↗

Von Willebrand's disease and pregnancy.

Seven new cases of pregnancy combined with von Willebrand's disease have been reported. Altogether the patients had 11 deliveries, and one abortion after 10 weeks' gestation. The diagnosis was based on the determination of the bleeding time, factor VIII coagulant activity (VIII C), factor VIII-related antigen (VIII RAg) and the ristocetin cofactor (VIII RCoF). Two of our 6 parturients showed profuse bleeding at delivery; in addition one patient showed bleeding after abortion at 10 weeks' gestation. Vaginal delivery is generally safe in patients with von Willebrand's disease. There is a great risk of copious bleeding especially in connection with early abortion, when factor VIII levels are low.

Abortion, Spontaneous↗

Thermography in the diagnosis of DVT.

161 consecutively admitted medical patients with the clinical suspicion of acute deep venous thrombosis (DVT) were thermographed and phlebographed in order to study the congruence of these methods. The sensitivity of thermography in the detection of DVT was found to be 99%, whereas the specificity was only 49%. The low specificity is explained by the fact that all thermographs suggestive of DVT were classified as pathologic to keep the sensitivity of the method as high as possible. Patients with dilated veins which may closely resemble DVT on thermography may in these cases give false positive results. Of 76 patients with phlebographically verified DVT, 22% became thermographically normal within 22 days, whereas 78% did not normalize within the mean observation time of 31 days. In another part of the study all medical patients (101) who were residing in our wards during a period of a week were screened by means of thermography. From this unselected group 17 patients were found to have thermographs suggestive of DVT. In 5 of these patients no reason for pathological thermography could be found. Thermography is a cheap and highly sensitive screening method for DVT, but findings of false positives caused by older thromboses and dilated veins are not unusual. The frequency of such false positives may be minimized by performing thermography after exercise.

Acute Disease↗