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  • 1.
    Aldrimer, Mattias
    et al.
    Department of Clinical Chemistry, County Hospital of Falun.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Department of Pediatrics, County Hospital of Falun.
    Niklasson, Frank
    Department of Clinical Chemistry, County Hospital of Falun.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Population-based pediatric reference intervals for hematology, iron and transferrin2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 253-261Article in journal (Refereed)
    Abstract [en]

    Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete. Blood samples were obtained from 689 healthy children, aged 6 months to 18 years, recruited in day care centers and schools. Hematology and anemia analytes were measured on the Siemens Advia 2120 and Abbott Architect ci8200 platforms (hemoglobin, erythrocyte volume fraction [EVF], erythrocytes, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], reticulocytes, leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets, iron, transferrin, transferrin saturation). Age-and gender-specific pediatric reference intervals were defined by calculating 2.5th and 97.5th percentiles. The data generated is primarily applicable to a Caucasian population, but could be used by any laboratory if verified for the local patient population.

  • 2. Aldrimer, Mattias
    et al.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Niklasson, Frank
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 4, p. 326-332Article in journal (Refereed)
    Abstract [en]

    Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

  • 3.
    Billström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Socioeconomic characteristics, housing conditions and criminal offences among women with cervical neoplasia2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 8, p. 888-894Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the association between cervical neoplasia and socioeconomic factors, housing conditions and criminal offences. Design. Longitudinal observational study. Setting. Falun county hospital, Sweden. Population. A total of 1331 women diagnosed with cervical intraepithelial neoplasia I-III or cervical cancer between 1967 and 1978 were compared with 2604 age-matched controls from the same geographical area in Sweden. Methods. The Population and Housing Censuses were used for information about civil status, education, housing conditions, employment and socioeconomic status. The Swedish Register of Conviction Decisions was used to access information on criminal offences. Main outcome measures. Socioeconomic status, housing conditions, criminal offences. Results. Women with cervical neoplasia had a lower socioeconomic status and a lower educational level than their age-matched controls. They were more often divorced and did not own their home as often as controls. A significant association with criminal offences was observed, and it persisted after adjustment for socioeconomic status. Differences in socioeconomic factors between women with cervical neoplasia and their controls had not diminished in the younger, compared with the older, part of the study population. Conclusions. The results indicate that women with cervical neoplasia belong to a socioeconomically disadvantaged group. Furthermore, the study provides information about an association with criminal offences.

  • 4.
    Edman, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Ctr Oral Rehabil, S-79127 Falun, Sweden..
    Ohrn, K.
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Nordstrom, B.
    Adm Ctr Publ Dent Serv, Falun, Sweden..
    Holmlund, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Natl Dent Serv Gavleborg, Gavle, Sweden.;Uppsala Univ Reg Gavleborg, Clin Res Ctr, Gavle, Sweden..
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Clin Res Ctr, Falun, Sweden..
    Trends over 30years in the prevalence and severity of alveolar bone loss and the influence of smoking and socio-economic factors: based on epidemiological surveys in Sweden 1983-20132015In: International Journal of Dental Hygiene, ISSN 1601-5029, E-ISSN 1601-5037, Vol. 13, no 4, p. 283-291Article in journal (Refereed)
    Abstract [en]

    ObjectiveEpidemiological studies of the prevalence of periodontitis over an extended time using the same methodology to investigate and classify periodontitis are sparse in the literature. Smoking and socio-economic factors have been proven to increase the risk for periodontal disease. The objective of this study was to investigate 30-year time trends, using the same methodology to classify the prevalence and severity in alveolar bone loss (ABL) and to investigate the influence of tobacco and socio-economic factors. MethodsFour cross-sectional epidemiological studies in an adult population were performed in the county of Dalarna, Sweden, in 1983, 2003, 2008 and 2013. Random samples of 787-1133 individuals aged 35-85 who answered a questionnaire about tobacco use and socio-economic factors were radiographically and clinically examined. A number of teeth, ABL and calculus visible on radiographs were registered. The severity of ABL as detected on radiographs was classified into no bone loss, moderate or severe. ResultsThe prevalence of moderate ABL decreased from 45% in 1983 to 16% in 2008, but increased to 33% in 2013 (P<0.05). The prevalence of severe ABL remained the same from 1983 (7%) to 2013 (6%). Calculus visible on radiographs increased from 22% in 2008 to 32% in 2013 (P<0.05). Socio-economic factors had limited impact on the severity of ABL. ConclusionModerate ABL and calculus visible on radiographs significantly increased between 2008 and 2013. Smoking was the strongest factor associated with ABL overall.

  • 5.
    Edman, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Ohrn, Kerstin
    Holmlund, Anders
    Nordstrom, Birgitta
    Hedin, Mans
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Comparison of oral status in an adult population 35-75 year of age in the county of Dalarna, Sweden in 1983 and 20082012In: Swedish Dental Journal, ISSN 0347-9994, Vol. 36, no 2, p. 61-70Article in journal (Refereed)
    Abstract [en]

    The aim was to study the prevalence and distribution of number of teeth, number of intact and decayed teeth and prevalence and distribution of removable dentures and periodontal disease over 25 years 1983-2008. Two cross-sectional studies (EpiWux) were performed in the County of Dalarna, Sweden in 1983 and 2008. In the 1983 study a random sample of 1012 individuals were invited to participate in this epidemiological and clinical study and 1440 individuals in 2008. A total number of 1695 individuals, stratified into geographical areas (rural and urban areas), in the age groups 35, 50,65 and 75 answered a questionnaire and were also clinically and radiographically examined. The number of edentulous individuals decreased from 15% in 1983 to 3 % in 2008. Number of teeth increased from 22.7 in 1983 to 24.2 in 2008 and decayed surfaces per tooth showed a three-time reduction over this period of time. As a consequence of better oral status the prevalence of complete removable dentures in both jaws decreased from 15 % in 1983 to 2 % in 2008. Individuals with moderate periodontitis decreased from 45 % in 1983 to 16 % in 2008. Conclusion: Covering a period of 25 years the present study can report dramatic improvements in all aspects of dental status that were investigated. This is encouraging for dental care professionals, but will not necessarily lead to less demand for dental care in the future as the population is aging with a substantial increase in number of teeth.

  • 6.
    Gremel, Gabriela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Djureinovic, Dijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maindad, Vikas
    Bharambe, Bhavana M.
    Khan, Wasif Ali Z. A.
    Navani, Sanjay
    Elebro, Jacob
    Jirstrom, Karin
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Uhlen, Mathias
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A systematic analysis of commonly used antibodies in cancer diagnostics2014In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 64, no 2, p. 293-305Article in journal (Refereed)
    Abstract [en]

    AimsImmunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. Methods and resultsA tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. ConclusionsThe results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.

  • 7.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Sex Steroids and Cervical Cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 8, p. 3045-3054Article, review/survey (Refereed)
    Abstract [en]

    During the 19th century, studies indicated that reproductive events were involved in cervical cancer. Human papillomavirus (HPV) infection is a prerequisite for development of cancer, but co-factors, among them the action of sexual steroid hormones, are necessary. Childbirth has been an important risk factor but now probably plays a minor role in the industrialized world, where parity is low. Longterm oral contraceptive use has been thoroughly studied epidemiologically, and correlates to cervical cancer in most studies. In vitro studies on cervical cell lines transfected with HPV and animal studies indicate that sex steroid hormones are capable to induce cancer. In in vivo cervical cancer tissue studies there have been observations that endogenous progesterone in serum correlates to a negative pattern of expression of cellular and extracellular proteins, tumor markers. Immune response could be another mechanism. Estradiol might be associated with a positive pattern and high estradiol and low progesterone levels increase duration of survival in cervical cancer. Studies where treatment of compounds that influence sex steroid hormones have been given are rare and have been disappointing.

  • 8.
    Hellberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Tot, Tibor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tumor Marker Score for Prognostication of Early-stage Squamous Cell Cervical Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 2, p. 887-892Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Histopathological and clinical scores to predict prognosis in cervical cancer have been of limited value. In the present study a tumor marker expression score was evaluated for prognostication in early-stage cervical cancer. Materials and Methods: The entire study population included 128 women with invasive squamous cell cervical cancer followed-up for at least 10 years. Results: Expression of 12 tumor markers (epidermal growth factor receptor (EGFR), Ki-67, c-MYC, p53, p27, E-cadherin, CD44, vascular endothelial growth factor receptor (VEGF), cyclooxygenase-2 (COX2), CD4, and leucine-rich immunoglobulin-like repeats-1 (LRIG1) and LRIG2, considered relevant for cervical cancer prognostication was evaluated by immunohistochemistry. Expression of five markers, LRIG1, LRIG2, p53, COX2 and c-MYC were useful to make a prognostication score, ranging from 0 to 5. Score 0-1 correlated to less than 5% 10-year mortality, while the mortality rate of those with score 4-5 approached 70%; those with score 2 formed an intermediate group. Using different models, a high sensitivity, specificity, positive predictive value and negative predictive value was attained. Conclusion: Tumor marker scoring could be an adjunct to histopathological and clinical parameters in prognostication of early-stage cervical cancer.

  • 9.
    Hofmeyer, Syster
    et al.
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Pekár, Gyula
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Gere, Mária
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Tarján, Miklós
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tot, Tibor
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Comparison of the subgross distribution of the lesions in invasive ductal and lobular carcinomas of the breast: a large-format histology study2012In: International journal of breast cancer, ISSN 2090-3189, Vol. 2012, p. 436141-Article in journal (Refereed)
    Abstract [en]

    To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586), multifocal in 35.5% (208/586), and diffuse in 1.2% (7/586) of the cases. The corresponding figures in the lobular group were 27.8% (37/133), 45.9% (61/586), and 26.3% (35/133), respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586), multifocal in 31.6% (185/586), and diffuse in 26.8% (157/586) of the cases. The corresponding figures in the lobular category were 15.0% (20/133), 54.2% (72/133), and 30.8% (41/133), respectively. Ductal cancers were extensive in 45.7% (268/586), lobular in 65.4% (87/133) of the cases. All these differences were statistically highly significant (P < 0.0001). While the histological tumor type itself (ductal versus lobular) did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers.

  • 10.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Medicinkliniken Mora Landstinget Dalarna.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna, Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum för klinisk forskning, Dalarna, Falun.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

    AIMS: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    METHODS AND RESULTS: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    CONCLUSIONS: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death.

  • 11.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum klinisk forskning Dalarna Falun.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wester, Per
    Medicin och folhälsa Umeå Universitet.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed)
    Abstract [en]

    Background Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.

    Methods and Results From the participants of the Vasaloppet, the world's largest ski‐race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first‐time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person‐years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.

    Conclusions This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 12.
    Lau, Nga M.
    et al.
    Department of Medicine, Columbia University, New York, USA.
    Green, Peter H. R.
    Department of Medicine, Columbia University, New York, USA.
    Taylor, Annette K.
    Kimball Genetics, a Division of LabCorp, Denver, Colorado, USA.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ajamian, Mary
    Department of Medicine, Columbia University, New York, USA.
    Tan, Caroline Z.
    Department of Medicine, Columbia University, New York, USA.
    Kosofsky, Barry E.
    Department of Neurology & Neuroscience, Weill Cornell Medical College, New York, USA.
    Higgins, Joseph J.
    Department of Pediatrics, Weill Cornell Medical College, New York, USA.
    Rajadhyaksha, Anjali M.
    Department of Neurology & Neuroscience, Weill Cornell Medical College, New York, USA.
    Alaedini, Armin
    Department of Medicine, Columbia University, New York, USA.
    Markers of Celiac Disease and Gluten Sensitivity in Children with Autism2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e66155-Article in journal (Refereed)
    Abstract [en]

    Objective: Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease. Methods: Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADIR) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles. Results: Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed. Conclusions: A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.

  • 13.
    Lindquist, D
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Tot, T
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Disease Extent ≥4 cm Is a Prognostic Marker of Local Recurrence in T1-2 Breast Cancer2011In: Pathology research international, ISSN 2042-003XArticle in journal (Refereed)
    Abstract [en]

    Despite improvements of the therapy for breast cancer, a proportion of the patients still get local recurrence. The status of the surgical margins is the most often used parameter for decision regarding additional treatment. However, a negative margin is not a guarantee that there is not residual cancer left in the breast; additional parameters are needed to better predict the risk of local recurrence. The disease extent was evaluated in the surgical specimen from 313 women after breast-conserving therapy using large-section histology and was correlated to the incidence of local recurrence. A disease extent ≥4 cm was shown to be an independent marker for local recurrence; the cumulative 10-year local relapse rate for the group with a disease extent ≥4 cm was 20.5%, and for the rest 6.7%. We conclude that disease extent ≥4 cm seems to be an important factor when evaluating the risk for local recurrence.

  • 14.
    Lindström, Annika K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Correlation between LRIG1 and LRIG2 expressions and expression of 11 tumor markers, with special reference to tumor suppressors, in CIN and normal cervical epithelium2011In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 122, no 2, p. 372-376Article in journal (Refereed)
    Abstract [en]

    Objective. Novel biological markers LRIG1 and LRIG2 have been associated with favorable as well as poor prognosis, respectively, in different cancer types, including cervical cancer. The aim of this study was to investigate possible interactions between these proteins and other tumor markers, and as diagnostic adjuncts in CIN. Methods. Cervical biopsies from 171 women, with normal epithelium, and low-grade and high-grade CIN were stained for LRIG1 and LRIG2, and 11 additional tumor markers. The tumor markers were chosen to be relevant in cervical neoplasms. Staining was evaluated semiquantitatively. Results. Expression of LRIG1 and LRIG2 was found to correlate with increasing CIN grade, as well as with expression of tumor suppressor FHIT, independent of histological grade. In addition, tumor promoter LRIG2 expression correlated negatively with expression of tumor suppressor retinoblastoma protein and positively with IL-10. The latter correlation did not however remain after adjustment for CIN grade. p53 and p16 expressions correlated positively with LRIG1 expression in univariate analyses, but significance did not hold after adjustment for CIN grade. Conclusion. LRIG1 and LRIG2 expressions were seen in precancerous cervical epithelium and found to increase with increasing grade. There was an association between expression of these glycoproteins and FHIT tumor suppressor protein, independently of histological grade.

  • 15.
    Lindström, Annika K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Immunohistochemical LRIG3 expression in cervical intraepithelial neoplasia and invasive squamous cell cervical cancer: association with expression of tumor markers, hormones, high-risk HPV-infection, smoking and patient outcome2014In: European journal of histochemistry, ISSN 1121-760X, E-ISSN 2038-8306, Vol. 58, no 2, p. 83-87Article in journal (Refereed)
    Abstract [en]

    The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, meno pausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and Ecadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cell cervical cancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influ-markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful.

  • 16. Moeller, Sina
    et al.
    Lau, Nga M.
    Green, Peter H. R.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Higgins, Joseph J.
    Rajadhyaksha, Anjali M.
    Alaedini, Armin
    Lack of association between autism and anti-GM1 ganglioside antibody2013In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 81, no 18, p. 1640-1641Article in journal (Other academic)
    Abstract [en]

    Forty of 54 children with autism were reported to have an elevated antibody response to GM1 ganglioside that correlated with disease severity.1 Antiganglioside autoantibodies, especially those directed at GM1, are known to be associated with and play a pathogenic role in some immune-mediated peripheral neuropathies.2,3 The presumed link between autism and anti-GM1 antibodies, therefore, implies that testing may identify a sizable subset of patients who would benefit from immunomodulatory therapy. To evaluate the proposed association between autism and anti-GM1 antibodies, serum samples from children diagnosed with autism by strict clinical criteria and those without autism were analyzed using a standard, validated immunoassay protocol.

  • 17.
    Pekar, Gyula
    et al.
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Falun, Sweden.
    Davies, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lukacs, Agnes P
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Falun, Sweden.
    Forsberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dumanski, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tot, Tibor
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Falun, Sweden.
    Biobanking multifocal breast carcinomas: sample adequacy with regard to histology and DNA content2016In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 68, no 3, p. 411-421Article in journal (Refereed)
    Abstract [en]

    AIMS: To determine the volume of tumoral and normal breast tissue containing sufficient DNA (>2 μg/sample) for genetic platforms and biobanking, with a focus on multifocality, tumoral heterogeneity, and factors that critically influence sample acceptability.

    METHODS AND RESULTS: We examined 57 breast surgical specimens with multifocal (46/57) and unifocal (11/57) cancers. Punch biopsies were obtained from tissue slices under multimodal radiological guidance, and the colour-coded sampling sites were identified in large-format histology slides. The study comprised 415 DNA isolations from tumour (n = 105) and normal (n = 283) tissue, including skin (n = 27) samples. A single 2-mm core from invasive tumour contained sufficient DNA in 91.4% (96/105) of cases, depending on tumour type (3.8-108.2 μg/sample), number and size of additional foci in multifocal cases (P = 0.001), tumour consistency, and degree of necrosis. Three biopsies obtained with a 4-mm device were required from normal breast tissue, at least 10 mm from the tumour. Cold ischaemia for up to 82 min did not influence the yield of DNA.

    CONCLUSIONS: Radiological disease mapping is useful for guiding optimal specimen slicing and for targeting breast lesions. A single 2-mm core from tumour and multiple 4-mm cores from normal breast tissue yield adequate DNA in the majority of samples.

  • 18.
    Pekar, Gyula
    et al.
    Central Hospital Falun, Department of Pathology and Clinical Cytology, Falun, Sweden.
    Gere, Maria
    Central Hospital Falun, Department of Pathology and Clinical Cytology, Falun, Sweden.
    Tarjan, Miklos
    Central Hospital Falun, Department of Pathology and Clinical Cytology, Falun, Sweden.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tot, Tibor
    Central Hospital Falun, Department of Pathology and Clinical Cytology, Falun, Sweden.
    Molecular Phenotype of the Foci in Multifocal Invasive Breast Carcinomas2014In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 120, no 1, p. 26-34Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Multiple synchronous, ipsilateral, invasive foci of breast carcinomas are frequent and are associated with a poorer prognosis. Few studies have investigated the prognostic and therapeutic implications of heterogeneity of such foci.

    METHODS The authors reviewed the tumor type, grade, and size of all invasive foci in a series of 110 multifocal breast carcinomas documented on large-format slides. Molecular phenotype was determined by immunohistochemistry in tissue microarray blocks using 3 classification systems. The survival of patients who had tumors with microscopic (tumor type and/or grade) heterogeneity and of those who had tumors with phenotypic heterogeneity was compared with the survival of patients who had multifocal homogeneous tumors using Kaplan-Meier curves. The hazard ratio of dying from breast cancer was also calculated.

    RESULTS Intertumoral heterogeneity in tumor type and grade was detected in 16 of 110 tumors (14.6%) and in 6 of 110 tumors (5.5%), respectively. The molecular phenotype of invasive tumor foci within the same breast differed in 10% to 12.7% of patients (11-14 of 110 tumors), depending on the classification system used. Patients who had phenotypically heterogeneous, multifocal cancers had a greater risk of dying from disease (HR=2.879; 95%CI=1.084-7.649; P=.034) and had significantly shorter survival (P=.016). Phenotypic differences were most common in patients who had tumors that were homogeneous in terms of tumor type (11 of 18 tumors) and histology grade (14 of 18 tumors). Phenotyping additional tumor foci had the potential to influence the therapeutic decisions in up to 8 patients.

    CONCLUSIONS Phenotyping more than 1 invasive focus of multifocal breast carcinomas only if the individual foci deviate microscopically appears to be insufficient, because phenotypic intertumoral heterogeneity may be observed in microscopically identical foci and has potential prognostic and therapeutic consequences. 

  • 19. Ridefelt, Peter
    et al.
    Aldrimer, Mattias
    Klinisk kemi, Laboratoriemedicin Dalarna, Falu Lasarett.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kreatininvärden bör kompletteras med GFR-beräkningar2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 110, p. 47-Article in journal (Other academic)
  • 20.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Aldrimer, Mattias
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Kreatininvärden bör kompletteras med GFR-beräkningar: [Creatinine values ​​should be complemented with GFR estimates]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 47Article in journal (Refereed)
  • 21.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Aldrimer, Mattias
    Rodoo, Per-Olof
    Niklasson, Frank
    Jansson, Leif
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Population-based pediatric reference intervals for general clinical chemistry analytes on the Abbott Architect ci8200 instrument2012In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 50, no 5, p. 845-851Article in journal (Refereed)
    Abstract [en]

    Background: Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete.

    Methods: Blood samples were obtained from 692 healthy children, aged 6 months to 18 years, recruited in daycare centers and schools. Twelve common general clinical chemistry analytes were measured on the Abbott Architect ci8200 platform; sodium, potassium, chloride, calcium, albumin-adjusted calcium, phosphate, magnesium, creatinine (Jaffe and enzymatic), cystatin C, urea and uric acid.

    Results: Age- and gender specific pediatric reference intervals were defined by calculating the 2.5th and 97.5th percentiles.

    Conclusions: The data generated is primarily applicable to a Caucasian population when using the Abbott Architect platform, but could be used by any laboratory if validated for the local patient population.

  • 22.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function. Klinisk kemi och farmakologi, Akademiska sjukhuset, Uppsala.
    Aldrimer, Mattias
    Rödöö, Peo
    Falu lasarett.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Niklasson, Frank
    Klinisk kemi, laboratoriemedicin Dalarna, Falu lasarett.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Referensintervall för barn för vanliga klinisk-kemiska analyser2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 43-44, p. 1927-1930Article in journal (Other academic)
  • 23.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Aldrimer, Mattias
    Rödöö, Peo
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Niklasson, Frank
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Referensintervall för barn för vanliga klinisk-kemiska analyser: [Pediatric reference ranges for clinical chemistry analyzes]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 43-44, p. 1927-1930Article in journal (Refereed)
    Abstract [sv]

    Tillförlitliga data för barnreferensintervall har länge varit en bristvara.

    I en prospektiv studie från Falun samlades blod från 701 friska barn. Referensintervall för ett 50-tal allmänkemiska och hematologiska analyser beräknades.

  • 24.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Aldrimer, Mattias
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels.2014In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no 6, p. 399-404Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transient hyperphosphatasemia (TH) is an often unnoticed benign entity, primarily affecting children below 5 years of age. However, the prevalence among healthy children is unknown. We used data from a Swedish pediatric reference interval project to estimate the prevalence of high alkaline phosphatase (ALP) among healthy children and to calculate pediatric reference intervals.

    METHODS: Blood was collected from 699 subjectively healthy children aged 6 months to 18 years. After exclusion of subjects with high ALP, age- and gender-specific reference intervals were calculated.

    RESULTS: Six children had ALP levels >16.7 µkat/l (>1,000 U/l), including 4 females and 2 males aged 7-22 months. The prevalence in the age group from 6 months to 2 years was 6.2% (6/97). None of the older children had levels of ALP >16.7 µkat/l. The study did not include the follow-up of these apparently healthy children. Consequently, conditions others than TH explaining the elevated ALP could not be excluded. However, general chemistry analyses, such as liver enzymes, calcium, intact PTH and vitamin D, were essentially normal in these children.

    CONCLUSIONS: The prevalence of high ALP among subjectively healthy children was approximately 2.4% below 5 years of age and 6.2% below 2 years. Reference intervals vary with age and gender.  

  • 25.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Aldrimer, Mattias
    Department of Clinical Chemistry, County Hospital of Falun, Sweden.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Estimating reliable paediatric reference intervals in clinical chemistry and haematology2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 1, p. 10-15Article, review/survey (Refereed)
    Abstract [en]

    Very few high-quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. ConclusionThe present review summarises current reference interval studies for common clinical chemistry and haematology analyses.

  • 26.
    Rodoo, Peo
    et al.
    Department of Pediatrics, Falun Hospital, Sweden.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Girls who masturbate in early infancy: diagnostics, natural course and a long-term follow-up2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 7, p. 762-766Article in journal (Refereed)
    Abstract [en]

    Aim To evaluate the natural course, onset, diagnostics and long-term follow-up masturbation in infant girls, which up to now has only been described in case reports. Methods Nineteen consecutive healthy, masturbating girls, diagnosed in early infancy between three and 15months, were followed up for an average of 8years. All were diagnosed in the same Swedish hospital between May 1996 and June 2010. Ten girls were videotaped and/or directly observed while masturbating. Results Mean age at onset of masturbation was 10.4months. The diagnosis was based on history taking and clinical observation. Parents reported that masturbation ranged from a few times a week to two-to-fifty episodes a day. Twelve girls had stopped masturbating when this study was written, after a mean duration of 66months. Their symptoms and diagnostics are described in detail. Conclusion This is the first follow-up study of girls who started masturbating in early infancy, with a mean duration of five-and-a-half years. Diagnosis may be difficult, but with awareness and knowledge of the condition, a normal physical and neurological examination, a detailed history from the parents and, in particular, video documentation, it can be settled without extensive investigations and the parents reassured.

  • 27.
    Rodoo, Peo
    et al.
    Department of Pediatrics, County Hospital of Falun.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Aldrimer, Mattias
    Department of Clinical Chemistry, County Hospital of Falun.
    Niklasson, Frank
    Department of Clinical Chemistry, County Hospital of Falun.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Population-based pediatric reference intervals for HbA1c, bilirubin, albumin, CRP, myoglobin and serum enzymes2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 5, p. 361-367Article in journal (Refereed)
    Abstract [en]

    Background. Many previous studies on reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. Methods. This study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy. A questionnaire on diseases and medications was filled out by parents and by the older children. Results. Alanine aminotransferase (ALT), albumin, aspartate aminotransferase (AST), bilirubin, conjugated bilirubin, C-reactive protein (CRP), creatine kinase (CK), Gamma-glutamyltransferase (GGT), HbA1c (mono S and IFCC calibrations), lactate dehydrogenase (LD), myoglobin and panceratic amylase were analyzed on Abbott Architect ci8200, and for HbA1c on Tosoh G7 and a mono S-system. Age-and gender-related 2.5th and 97.5th percentiles were estimated. For some analytes the differences to comparable studies were substantial. Conclusion. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results emphasize the importance to evaluate pediatric reference intervals in different populations and ethnic groups including only healthy subjects.

  • 28.
    Samir, Raghad
    et al.
    Department of Obstetrics and Gynecology, Falun Hospital.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tot, Tibor
    Department of Pathology and Clinical Cytology, Falun Hospital.
    Pekar, Gyula
    Department of Pathology and Clinical Cytology, Falun Hospital.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    High-Risk HPV Infection and CIN Grade Correlates to the Expression of c-myc, CD4(+), FHIT, E-cadherin, Ki-67, and p16(INK4a)2011In: Journal of Lower Genital Tract Disease, ISSN 1089-2591, E-ISSN 1526-0976, Vol. 15, no 4, p. 280-286Article in journal (Refereed)
    Abstract [en]

    Objective. This study aimed to investigate correlations between a panel of biomarkers/tumor markers and high-risk (HR) human papillomavirus (HPV)-positive versus HR-HPV-negative cervical lesions.

    Materials and Methods. The study included 188 women who consecutively attended a colposcopy clinic because of PAP smears suggesting cervical intraepithelial neoplasia (CIN), and 40 women with normal vaginal cytology. Tissue microarray blocks were prepared from representative cervical cone or punch biopsies. Sections were stained for 12 biological markers, previously shown to be relevant in cervical neoplasms, and expression was correlated to the presence or absence of HR-HPV in cervical lesions.

    Results. No correlations between expression of biomarkers and HPV status were found in normal epithelium. Expression of c-myc, CD4(+), Ki-67, and p16(INK4a) correlated significantly to HR-HPVYinfected epithelium compared with HR-HPV-negative epithelium. When adjustment was made for CIN grade, only the expression of Ki-67 correlated significantly with HPV status and CIN grade. Human papillomavirus status was stratified to normal epithelium, low-grade CIN, and high-grade CIN. Fragile histidine triad (FHIT), E-cadherin, Rb, Ki-67, and p16(INK4a) expression was significantly increased in HPV-positive tissue by increasing CIN grade. No correlation to tumor marker expression was observed in the HPV-negative tissue. Conclusions. This study described correlations, previously not investigated, between HPV status and tumor marker expression, that is, E-cadherin, Rb, and fragile histidine triad. Surprisingly, p16(INK4a) was not, although Ki-67 expression was, independently correlated to HPV positivity. The results of this study suggest that p16(INK4a) instead correlates independently with increasing CIN grade.

  • 29. Samir, Raghad
    et al.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Tot, Tibor
    Pekar, Gyula
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oral contraceptive and progestin-only use correlates to tissue tumor marker expression in women with cervical intraepithelial neoplasia2012In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 85, no 3, p. 288-293Article in journal (Refereed)
    Abstract [en]

    Background: The study was conducted to investigate correlations between combined oral contraceptive (COC), any progestin-only contraceptive, medicated intrauterine device (MID) or systemic progestin-only (Syst-P) use and tumor marker expression in cervical intraepithelial neoplasia compared to nonusers.

    Study Design: One-hundred ninety-five women of fertile age with cervical biopsies ranging histologically from normal epithelium to carcinoma in situ were recruited consecutively. Combined oral contraceptive, Syst-P and MID users were investigated according to the expression of 11 tumor markers.

    Results: Overexpression of cyclooxygenase-2 (Cox-2) was observed in COC users, while interleukin 10 was underexpressed. When users of progestogen-only contraceptives were analyzed, there was a lower expression of cytokeratin 10 and interleukin 10. When only MID users were analyzed, a high expression of p53 was found. Expression of Cox-2, p53 and retinoblastoma protein differed between COC and MID users.

    Conclusion: The study showed molecular alterations, which, in general, have not been studied previously in COC users and have never been studied in progestogen-only users. These biological events might be involved in epidemiological correlations found between hormonal contraceptive use and cervical neoplasms.

  • 30.
    Stenberg, Reidun
    et al.
    Dept of Paediatrics, Centre for Rehabilitation Research, Örebro University Hospital, .
    Dahle, Charlotte
    Clinical Immunology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistic Unit, Örebro University Hospital, Sweden.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Tysk, Curt
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital.
    Increased Prevalence of Antibodies Against Dietary Proteins In Children And Young Adults With Cerebral Palsy2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 56, no 2, p. 233-238Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Undernourishment is common in children with cerebral palsy (CP) but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG-antibodies against other dietary antigens, AGA, anti-tTG and IgE-antibodies against wheat and gluten.

    METHODS:

    Sera from 99 CP-cases and 99 healthy, age- and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay(FEIA) for detection of IgG-antibodies against beta-lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG and IgE antibodies against gluten and wheat.

    RESULTS:

    Compared with controls, the odds ratio (OR) in CP cases for having elevated levels of IgG antibodies against beta-lactoglobulin was 17.0 (95% CI 2.3-128), against casein 11.0 (95% CI 2.6-46.8) and against egg white 7.0 (95% CI 1.6-30.8). The IgE-responses for wheat/gluten were generally low. The tetraplegic (TP) and dyskinetic (DK) CP-subtypes had significantly higher frequencies of elevated levels for all tested antibodies except IgG against egg white, and IgA-anti- tTG. A significantly lower weight was seen in CP-cases with positive versus negative serology.

    CONCLUSION:

    Elevated levels of IgG against dietary antigens were more frequent in the CP-group compared with controls, and particularly in the TP and DK CP-subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.

  • 31. Tarjan, Miklos
    et al.
    Lenngren, Anna
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Tot, Tibor
    Immunohistochemical verification of ductal differentiation in prostate cancer2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 6, p. 510-518Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that patients with prostate carcinomas exhibiting ductal differentiation have an unfavourable prognosis compared with those with purely acinar adenocarcinomas. We studied the expression of nine immunohistochemical markers to evaluate their value in delineating carcinomas with and without ductal differentiation. Thirteen tumours showing cellular characteristics and growth patterns typical of ductal differentiation were identified among 110 analysed prostatectomy specimens. The levels of cytoplasmic expression of chromogranine A (69% vs 19%, p = 0.0003) and nuclear expression of p53 (76% vs 12%, p < 0.0001) as well as nuclear expression of Ki-67 (69% vs 26%, p = 0.0047) in the tumour cells, were found to be statistically significantly different in the two tumour categories. Assessment of chromogranine A, p53 and Ki-67 in prostate carcinoma may serve as useful adjunctive diagnostic tools for delineating more aggressive prostate cancer cases exhibiting ductal differentiation.

  • 32.
    Tot, Tibor
    et al.
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Pekár, Gyula
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Hofmeyer, Syster
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Gere, Maria
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Tarján, Miklós
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lindquist, David
    Department of Pathology and Clinical Cytology, Central Hospital Falun, Sweden.
    Molecular phenotypes of unifocal, multifocal, and diffuse invasive breast carcinomas2011In: Pathology research international, ISSN 2042-003XArticle in journal (Refereed)
    Abstract [en]

    We analyzed the subgross distribution of the invasive component in 875 consecutive cases of breast carcinomas using large-format histology sections and compared the immunophenotype (estrogen and progesterone receptor expression, HER2 overexpression and expression of basal-like markers, CK5/6, CK14, and epidermal growth factor receptor) in unifocal, multifocal, and diffuse tumors. Histology grade and lymph node status were also analyzed. Unifocal invasive carcinomas comprised 58.6% (513/875), multifocal invasive carcinomas 36.5% (319/875), and diffuse invasive carcinomas 4.9% (43/875) of the cases. The proportion of lymph node-positive cases was significantly higher in multifocal and diffuse carcinomas compared to unifocal cancers, but no other statistically significant differences could be verified between these tumor categories. Histological multifocality and diffuse distribution of the invasive tumor component seem to be negative morphologic prognostic parameters in breast carcinomas, independent of the molecular phenotype.

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