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PubMed2003

Individual quality assessment of autografting by probability evaluation: a model estimated by analysis of graft-related end points in 204 patients with malignancies.

Haematological toxicity is considered a secondary end point important for graft evaluation - in today's practice graft evaluation focuses on the primary impact of health economic end points. This report illustrates the benefit of combining CD34 enumeration and demographic as well as disease-related variables in models for individual quality assessment of autografting following high-dose therapy. A total of 24 centres in Scandinavia enrolled 204 patients younger than 67 years who received high-dose therapy with autologous peripheral blood stem cell transplantation. Using the binary Logistic Regression Analysis, the prognostic value of diagnostic demographic variables, therapy and graft-related factors was entered into a multivariate analysis and the final significant models were used to estimate probabilities for acceptable or unacceptable outcome among different patient scenarios. The model that estimated post-transplant efficacy by selected primary end points (time on antibiotics and use of transfusions) includes six independent variables related to sex, age, disease, conditioning, growth factor administration, and graft CD34+ cell number. The model that estimated transplantation-related toxicity by selected secondary end points (time to blood cell recovery) included four independent variables related to age, disease, growth factor administration and graft CD34+ cell number.

Adolescent↗
PubMedDate not supplied

Detailed mapping of the phosphomannomutase 2 (PMM2) gene and mutation detection enable improved analysis for Scandinavian CDG type I families.

The gene for carbohydrate-deficient glycoprotein syndrome type I (CDG1) has previously been localised by us close to marker D16S406 in chromosome region 16p13.2-3. We also presented data indicating a strong founder mutation associated with a specific haplotype in CDG I patients from western Scandinavia. The phosphomannomutase 2 (PMM2) gene was recently put forward as a likely CDG1 candidate gene. We have now shown that the specific haplotype is associated with the PMM2 mutation 357C > A. Using data from radiation hybrid panel we have refined the position of the PMM2 gene to very close to marker D16S3020 in the interval between D16S406 and AFM282ze1 on the distal side and D16S3087 on the proximal side. Due to the severity of the disease many families request prenatal diagnostic services for CDG I. In the meantime, until the mutation spectrum is fully examined, we propose the combined use of mutation analysis and linkage analysis with polymorphic markers as diagnostic tools for Scandinavian CDG I families requesting prenatal diagnosis. Using this strategy we have to date successfully performed 15 prenatal diagnoses for CDG I.

Base Sequence↗
PubMed2002

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited.

Phenylketonuric and hyperphenylalaninaemic patients in the population of the Republic of Ireland were screened for mutations at the human phenylalanine hydroxylase (PAH) locus. A composite data set for the island of Ireland was generated by merging the findings of this study with extant data for Northern Ireland. Analysis of this data on the basis of the four historic provinces (Munster, Leinster, Connacht and Ulster) revealed genetic diversity that is informative in terms of demographic forces that shaped the Irish population. R408W, the predominant Irish PAH mutation associated with haplotype 1.8, reached its highest relative frequency in the most westerly province, Connacht. This suggests that the gradient of R408W-1.8 observed across north-western Europe continues into Ireland and peaks in Connacht. Spatial autocorrelation analysis demonstrated that the gradient is consistent with a localised cline of R408W-1.8 likely to have been established by human migration. This and parallel allele frequency clines may represent the genetic traces of the Palaeolithic colonisation of Europe, a pattern not substantially altered in north-western Europe by subsequent Neolithic migrations. An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%. Mutations primarily associated with Scandinavia accounted for 6.1% of mutations overall, illustrating the influence of Viking incursions on Irish population history.

Amino Acid Substitution↗
PubMed2004

NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

NOD2/caspase recruitment domain (CARD)15 variants are identified in up to 50% of Crohn's disease (CD) patients. Functional variants of toll-like receptor-4 (TLR4) and CD14 genes may also be relevant to disease pathophysiology. We aimed to assess the contribution of NOD2/CARD15, TLR4 and CD14 variants in Scottish and Irish CD patients. In all, 612 patients with well-characterised inflammatory bowel disease (252 Scottish CD, 247 Scottish UC, 113 Irish CD) and 304 controls were genotyped for variants of NOD2/CARD15 (1007fsinsC, G908R, R702W, P268S), TLR4 (A299G) and CD14 (T-159C). Genotype-phenotype analyses were performed. Variant 1007fsinsC (P=0.003) and G908R (P=0.008) but not R702W (P=0.269) alleles were more prevalent in Scottish CD (4.7, 1.8 and 7.1%, respectively) than Scottish control (2.3, 0.3 and 5.4%). CD allelic frequencies were lower than the series from Europe (P<0.00001) and North America (P<0.00001) but not Scandinavia (P<0.7). Associations were identified with age at diagnosis (P=0.002), ileal disease (P<0.02), penetrating disease (P=0.04) and inflammatory joint disease (P<0.02). TLR4 and CD14 variants did not differ between CD and controls. In conclusion, we present compelling evidence for genetic heterogeneity within Europe. These NOD2/CARD15 variants have a minor contribution in Scottish and Irish CD patients, consistent with an emerging pattern from Northern Europe.

Adult↗
PubMed2005

Genetic evidence for a family-based Scandinavian settlement of Shetland and Orkney during the Viking periods.

The Viking age witnessed the expansion of Scandinavian invaders across much of northwestern Europe. While Scandinavian settlements had an enduring cultural impact on North Atlantic populations, the nature and extent of their genetic legacy in places such as Shetland and Orkney is not clear. In order to explore this question further, we have made an extensive survey of both Y-chromosomal and mitochondrial DNA (mtDNA) variation in the North Atlantic region. Our findings indicate an overall Scandinavian ancestry of approximately 44% for Shetland and approximately 30% for Orkney, with approximately equal contributions from Scandinavian male and female subjects in both cases. This contrasts with the situation for the Western Isles, where the overall Scandinavian ancestry is less ( approximately 15%) and where there is a disproportionately high contribution from Scandinavian males. In line with previous studies, we find that Iceland exhibits both the greatest overall amount of Scandinavian ancestry (55%) and the greatest discrepancy between Scandinavian male and female components. Our results suggest that while areas close to Scandinavia, such as Orkney and Shetland, may have been settled primarily by Scandinavian family groups, lone Scandinavian males, who later established families with female subjects from the British Isles, may have been prominent in areas more distant from their homeland.

Chromosomes, Human, Y↗
PubMed2000

Epidemiology of erectile dysfunction: results of the 'Cologne Male Survey'.

The last few decades have seen a marked increase in mean life expectancy in Central Europe. This has made elderly people and their quality of life a matter of ever-increasing medical concern. Available data from the United States and Scandinavia relating to erectile dysfunction (ED) do not enable us to draw valid conclusions about the current situation in Germany. The aim of the present study was to evaluate the epidemiology of male sexuality in Germany, and the proportion of men who need medical treatment because of increased suffering from this.A newly developed and validated questionnaire on male erectile dysfunction was mailed to a representative population sample of 8000 men, 30-80 y of age in the Cologne urban district. The response included 4489 evaluable replies (56.1%). The response rates in different age groups ranged from 49.2% to 68.4%. Regular sexual activity was reported by 96.0% (youngest age group) to 71.3% (oldest group). There were 31.5%-44% of responders who were dissatisfied with their current sex life. The prevalence of ED was 19.2%, with a steep age-related increase (2.3-53.4%) and a high co-morbidity of ED with hypertension, diabetes, pelvic surgery and 'lower urinary tract symptoms'. When treatment need was defined by co-occurrence of ED and dissatisfaction with sex life, 6.9% men required treatment for ED. Oral treatment of ED was preferred by 73.8% of respondents. There were 46.2% respondents who were willing to contribute more than DM 50 (25 Euro) per month for ED treatment. We conclude that regular sexual activity is a normal finding in advanced age. ED is a frequent disorder, contributing to dissatisfaction with sex life in a considerable proportion of men. The high burden of ED is reflected in willingness to pay for treatment. ED is frequently associated with chronic diseases. Therefore adequate diagnostic workup is essential, to offer patients individually adapted treatment. General non-reimbursability of treatment for ED appears to be unacceptable.

Adult↗
PubMed2000

The mercury sphygmomanometer should be abandoned before it is proscribed.

Both in clinical practice and medical research, blood pressure is still largely measured by auscultation using a mercury sphygmomanometer. Blood pressure is the most important predictor of life expectancy. Treatment of high blood pressure reduces strokes, heart attack and heart failure. Accurate measurement is therefore essential. At a large London teaching hospital, just under 500 mercury sphygmomanometers and their associated cuffs were examined. More than half had serious problems that would have rendered them inaccurate in measuring blood pressure. At the same time, assessment of the technical knowledge needed to measure blood pressure by the ausculatory technique was also carried out amongst medical and nursing staff. This showed a considerable level of ignorance. These results inevitably lead to inaccurate measurement of blood pressure with serious consequences. In addition mercury is a non-degradable pollutant, eventually accumulating on the sea bed. The use of mercury in sphygmomanometers is already in the process of being eliminated in Scandinavia and Holland and other countries are likely to follow. Our results suggest that mercury sphygmomanometers are not adequately maintained and require expertise that is not available for accurate measurement of blood pressure. Their use should be dispensed with on these grounds before a ban for other and, perhaps less justifiable reasons. Validated automatic devices, which are less liable to measurement and observer error should be used instead. At the same time a concerted effort is needed to instruct health care professionals on the importance of more accurate measurement of blood pressure. Journal of Human Hypertension (2000) 14, 31-36.

Adult↗
PubMed2004

Photogeneration of singlet oxygen by humic substances: comparison of humic substances of aquatic and terrestrial origin.

The singlet oxygen (1(O2)) luminescence of 27 isolated humic substances (HS), natural organic matter, ultrafiltrates, and the synthetic fulvic acid HS1500 has been investigated by time-resolved spectroscopy in buffered D(2)O. The samples include both reverse osmosis isolates from lakes in Scandinavia, Canada, and Germany, and IHSS fulvic and humic acids of aquatic and terrestrial origin. The quantum yields of 1(O2) formation (PhiDelta) obtained on laser excitation at 480 nm ranged between 0.06 (HS1500) and 2.7%(fulvic acid from soil, IHSS). In our study, a general trend towards higher PhiDelta in terrestrial HS was observed. The comparison of reverse osmosis isolates from surface waters collected during fall 1999 and spring 2000 from five Scandinavian sites yielded, in all cases, higher PhiDelta for the spring samples. For the aquatic sampling sites Hietajarvi and Birkenes, PhiDelta even exceeded values of 0.6%, which were found to be typical for terrestrial or soil water material. Investigation of the excitation wavelength dependence of PhiDelta in the spectral range 355-550 nm yielded different spectral shapes for aquatic HS and "non-aquatic" HS, respectively. On the basis of these excitation spectra, 1(O2) production rates were calculated for eight representative HS.

Journal Article↗
PubMed2003

Feasibility and utility of microsatellite markers in archaeological cattle remains from a Viking Age settlement in Dublin.

Nineteen cattle bones from the Viking 10th and early 11th century levels in Dublin were assessed for presence of reliable genotypes from three autosomal markers. Due to the good preservational condition of the samples, it was possible to amplify and type at least two out of three of the microsatellite markers (CSRM60, HEL1 and ILSTS001) in 11 specimens. Full three-loci genotypes were obtained from a subset of seven of these samples. A comparative analysis was performed using data from the same three markers in 11 extant British, Irish and Nordic cattle breeds. Although the medieval remains displayed lower levels of diversity than the modern European breeds, the results fit within the ranges obtained from the extant populations. The results indicate a probable origin for the ancient Irish cattle as the remains group significantly more closely with breeds from the British Isles than with those from Scandinavia. The data collected indicate that microsatellites may be useful for the further study of ancient cattle.

Animals↗
PubMed2001

Molecular studies on the colonization of the Madeiran archipelago by house mice.

To study the colonization history of the house mouse (Mus musculus domesticus) on the Madeiran archipelago, complete mitochondrial D-loop sequences were obtained for 44 individuals from Madeira, Porto Santo and Ilhas Desertas. Altogether, 19 D-loop haplotypes were identified which formed part of a single clade in a phylogeny incorporating haplotypes from elsewhere in the range of M. m. domesticus, indicating that the Madeiras were colonized from a single source. Similarities between the sequences found in the Madeiras and those in Scandinavia and northern Germany suggest that northern Europe was the source area, and there is the intriguing possibility that the Vikings may have accidentally brought house mice to the archipelago. However, there is no record of Vikings visiting the Madeiras; on historical grounds, Portugal is the most likely source area for Madeiran mice and further molecular data from Portugal are needed to rule out that possibility.

Animals↗
PubMed2003

Allergic sensitization among adults in Tallinn, Estonia.

BACKGROUND: The prevalence of allergic sensitization has increased worldwide during recent years. OBJECTIVE: The aim of the study was to estimate the prevalence of allergic sensitization and to evaluate the influence of age, gender, number of siblings, pet keeping in childhood, and residential area before the age of five on allergic sensitization among adolescents and adults aged 17-66 years in the capital of Estonia, Tallinn. A cross-sectional study was carried out between March 1997 and December 1998. METHODS: The sensitization to 15 inhalant allergens was assessed. The associations between sensitization based on skin prick tests (SPTs), symptoms based on a structured interview, and possible risk factors were estimated. A random sample of 516 subjects was included in the study analysis. RESULTS: The prevalence of allergic sensitization was 34.5%, while it was 39.3% in subjects aged 20-44 years. The most prevalent sensitization was against the German cockroach, 15.5%, and it was particularly high among adolescents. It was followed by mugwort, dog, two storage mites species, and cat dander. Subjects with wheezing during the last 12 months, attacks of shortness of breath, wheezing due to furred animals, and allergic rhinitis or conjunctivitis had a significantly higher prevalence of positive SPT. CONCLUSION: We found a surprisingly high prevalence of allergic sensitization among adults in Tallinn. Our results suggest that the cockroach allergen should be included in the investigation panel in order to reach a true prevalence of allergic sensitization in Estonia. Further, the pattern of allergic sensitization in Estonia appears to be different from published data about allergic sensitization in Scandinavia.

Adolescent↗
PubMed1998

Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence.

Epithelial ovarian cancer is fairly common with high rates in Scandinavia, intermediate rates in western Europe and North America and low rates in the developing countries and in Japan. The 5-year survival rate is less than 40%. Increasing parity consistently gives a strong protection against epithelial ovarian cancer. A lesser degree of protection is probably derived from incomplete pregnancies and lactation. Ages at menarche and menopause are most probably weak predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives (OC) have 30% lower risk compared to never users. The protection increases with duration of OC use, being about 50% after 5 years. The reduced risk among past OC users persists for at least 10 years after cessation of use. Results concerning hormone replacement therapy (HRT) and epithelial ovarian cancer risk are conflicting, but most data point to a weak or no association, but as an increasing number of women use HRT it still seems important to resolve any potential effect. Infertility adds to epithelial ovarian cancer risk in nulliparous women, while temporary fertility problems in parous women do not appear to increase risk. A possible independent risk effect of fertility drug use has not been easy to assess and remains unresolved. It has been particularly difficult to separate the effects of fertility drugs from those of infertility. Tubal ligation and hysterectomy convey protection against epithelial ovarian cancer, possibly through a suppressed ovarian hormone production. The causes of epithelial ovarian cancer are poorly understood, but reproductive hormones are thought to be involved in the aetiology. For a long time the 'incessant' and 'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both hypotheses find support in ovarian cancer epidemiology, and recent progress in molecular biology adds to the understanding of possible aetiological mechanisms. Another hypothesis focuses on the retrograde transport of contaminants or carcinogens through the Fallopian tubes. It is important to establish if the same risk factors apply to the various histological types of ovarian cancer, as particularly the mucinous ovarian tumours seem to present with different risk factors. Another question to resolve is if sporadic vs. inherited cases carry distinct risk profiles. As the hypotheses above do not explain all of the results derived from ovarian cancer epidemiology, there is a need to test additional hypotheses to possibly define preventive programmes and to come closer to the cause of ovarian cancer.

Adenocarcinoma↗
PubMed2003

Implementation of liquid-based cytology in the screening programme against cervical cancer in the County of Funen, Denmark, and status for the first year.

As one of the first laboratories in Denmark (and Scandinavia), we have gradually implemented liquid-based cytology into the screening programme against cervical cancer in the County of Funen since 1 June 2001. This paper describes the course of the implementation period in the different steps in the screening programme, and the preliminary results obtained after the first year. We conclude that the new technique has improved the specimen and diagnostic quality. As a result of the reduction of the screening time, the workload in the laboratory is in balance although we have introduced a rapid review as a quality control. Besides, the reduction in the number of repeated cytological tests and follow-up visits at the gynaecologist means a saving for the screening programme as a whole. From our point of view the implementation of ThinPrep method is economically neutral.

Adult↗
PubMed1996

Continuous vectorcardiographic changes in relation to scintigraphic signs of reperfusion in patients with acute myocardial infarction receiving thrombolytic therapy.

OBJECTIVES: Changes in the electrical activity of the heart reflecting the infarct process can be recorded by continuous vector-ECG, a method which is now clinically available for cardiac supervision. Shifts of the ST-segment and QRS-vector reflect ischaemia and necrosis of the myocardium. Continuous vector-ECG changes were evaluated against myocardial scintigraphy in 18 patients with acute myocardial infarction treated with streptokinase in order to study the impact of improved myocardial perfusion. DESIGN: Myocardial perfusion was analysed with 99Tcm-Sestamibi (Cardiolite, DuPont Scandinavia AB, Kista, Sweden) single photon emission computerized tomography (SPECT). Registrations were performed before and after thrombolysis in order to estimate the amount of myocardium with impaired perfusion initially (threatened myocardium) and the degree of perfusion improvement in this myocardial area. X, Y, Z vectors were registered continuously by Frank leads (Ortivus Medical, Täby, Sweden). QRS-vector difference, and the time to plateau phase and the ST-vector magnitude were used as a measurement of ischaemia and size of the myocardial infarction. RESULTS: In seven out of 11 patients treated within 3 h of onset of symptoms, an improvement in myocardial perfusion in the initially hypoperfused areas was achieved in contrast to none of the seven patients treated > 3 h after onset of pain (P < 0.05). In the whole patient material, there was a negative correlation between the time to plateau level for the QRS-vector and the improvement in myocardial perfusion (r = -0.53, P < 0.05). Among patients treated within 3 h, there was a negative correlation between the plateau level for the QRS-vector magnitude compared to the improvement in myocardial perfusion (r = -0.61, P < 0.05) and a negative correlation between the plateau level and the myocardial perfusion level after therapy (r = -0.69, P < 0.05). In these patients, there were also negative correlations between the maximal ST-vector magnitude and the myocardial perfusion both before and after thrombolysis (r = -0.81, P < 0.05 and r = -61, P < 0.05, respectively). CONCLUSION: Patients with marked improvement in myocardial perfusion indicating successful thrombolysis reach their plateau levels of the QRS-change faster and have lower total QRS-vector differences than patients without successful thrombolysis as reflected by myocardial scintigraphy. Patients with a high ST-vector magnitude have low perfusion levels both before and after therapy indicating a pronounced ischaemic damage of the myocardium. Thus, VCG-changes reflect impairment in myocardial perfusion during acute myocardial infarction.

Aged↗
PubMed2002

Cerebrotendinous xanthomatosis: molecular characterization of two Scandinavian sisters.

Cerebrotendinous xanthomatosis (CTX) is a hereditary disorder, which is inherited as an autosomally recessive disease, causing production of cholesterol and cholestanol xanthomas and mental retardation. The disease is caused by mutations in the gene for sterol 27-hydroxylase (CYP27A1). The only CTX patients diagnosed in Scandinavia are two Norwegian sisters from a consanguineous marriage. Here we have characterized the mutation and its functional consequences for the enzyme. Analysis of genomic DNA from cultured fibroblasts identified a base exchange C > T in position 1441, causing arginine at amino acid position 441 to be replaced by tryptophan. The same mutation was introduced by mutagenesis in the complimentary DNA (cDNA) for CYP27, ligated into the expression vector pcDNA4/HisMax and transfected into HEK293 cells. The mutated enzyme had less than 5% of the enzyme activity compared with the native enzyme. No abnormal catalytic products could be identified in the cell culture medium. Probably the mutation affects the haem binding within the holoenzyme. The mutation has also previously been reported in a Japanese family. This is the second example of a CTX-causing mutation that has been recognized in more than one population.

Adult↗
PubMed2003

The Arctic Oscillation and incidence of acute myocardial infarction.

OBJECTIVES: To describe the relation between the Arctic Oscillation (AO) index and the incidence and mortality in acute myocardial infarction (AMI) in the northern, partly subarctic area of Sweden. DESIGN: Comparison of a time series of daily variations in the AO index and register data on the daily number of fatal and nonfatal AMIs. SETTING: The northernmost two Swedish counties, Norrbotten and Västerbotten. SUBJECTS: All inhabitants in the Norrbotten and Västerbotten counties were followed for the occurrence of an AMI between 1985 and 1999 within the framework of the WHO MONICA (multinational MONItoring of trends and determinants of CArdiovascular disease) Project. MAIN OUTCOME MEASURE: Fatal and nonfatal AMIs. RESULTS: There was a consistent positive relation between increasing AO index and an increase in AMI incidence and mortality. The maximum impact on AMI incidence of the AO came after a lag phase of 3 days. A one unit increase in AO index was associated with an increase in: the daily number of AMIs (+3.8%), the case fatality in AMI within 28 days (+5.1%), the number of nonfatal AMIs (+3.4%), and the number of sudden cardiac deaths (+8.3%). CONCLUSIONS: An AO index increase, bringing warmer weather over Scandinavia, was associated with an increase in the incidence and mortality in AMI in northern Sweden.

Arctic Regions↗
PubMed1997

The occurrence of mountain hare mitochondrial DNA in wild brown hares.

If interspecific hybrids are fertile and backcross to either parental species, transmission of mitochondrial DNA over the species barrier can occur. To investigate if such transmission has occurred between the brown hare Lepus europeus Pall and the mountain hare L. timidus L. in Scandinavia, an analysis of genetic variation in mitochondrial DNA from 36 hares, collected from 15 localities, was performed. Sequence divergence of mtDNA between species was estimated at 8 +/- 1% (SD). Intraspecific mtDNA sequence divergence varied between 0.09 and 0.38% in brown hares and 0.10 and 1.44% in mountain hares. In six out of 18 brown hares examined, two different haplotypes of mountain hare origin were detected, demonstrating a transmission of mtDNA haplotypes from mountain hares to brown hares. The results indicate that interspecific hybridization between the two species occurs in wild populations.

Animals↗
PubMed2001

Y chromosome haplotyping in Scandinavian wolves (Canis lupus) based on microsatellite markers.

The analysis of mitochondrial DNA sequences has for a long time been the most extensively used genetic tool for phylogenetic, phylogeographic and population genetic studies. Since this approach only considers female lineages, it tends to give a biased picture of the population history. The use of protein polymorphisms and microsatellites has helped to obtain a more unbiased view, but complementing population genetic studies with Y chromosome markers could clarify the role of each sex in natural processes. In this study we analysed genetic variability at four microsatellite loci on the canid Y chromosome. With these four microsatellites we constructed haplotypes and used them to study the genetic status of the Scandinavian wolf population, a population that now contains 60-70 animals but was thought to have been extinct in the 1970s. In a sample of 100 male wolves from northern Europe we found 17 different Y chromosome haplotypes. Only two of these were found in the current Scandinavian population. This indicates that there should have been at least two males involved in the founding of the Scandinavian wolf population after the bottleneck in the 1970s. The two Scandinavian Y chromosome haplotypes were not found elsewhere in northern Europe, which indicates low male gene flow between Scandinavia and the neighbouring countries.

Animals↗