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Fürst Medisinsk Laboratorium driver aktiv forskning innenfor laboratoriemedisin, både for å holde seg oppdatert på fagområdet og for å bidra til videreutvikling av faget.

• Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study

  Forfattere: Kristiansen MS, Stabursvik J, O'Leary EC, Pedersen M, Asprusten TT, Leegaard T, Osnes LT, Tjade T, Skovlund E, Godang K, Wyller VBB
  Publisert i: Brain, Behavior, and Immunity Available online 27 April 2019 In Press

  • Les utdrag

    INTRODUCTION:

    Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to explore clinical symptoms as well as markers of disease mechanisms in fatigued and non-fatigued adolescents 6 months after EBV-infection, and in healthy controls.

    MATERIALS AND METHODS:

    A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed 6 months after the initial infectious event and divided into fatigued (EBV CF+) and non-fatigued (EBV CF-) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of 70 healthy controls with similar distribution of sex and age was included. Symptoms were mapped with a questionnaire. Laboratory assays included EBV PCR and serology; detailed blood leukocyte phenotyping and serum high-sensitive C-reactive protein; and plasma and urine cortisol and catecholamines. Assessment of autonomic activity was performed with continuous, non-invasive monitoring of cardiovascular variables during supine rest, controlled breathing and upright standing. Differences between EBV CF+ and EBV CF- were assessed by simple and multiple linear regression adjusting for sex as well as symptoms of depression and anxiety. A p-value ≤ 0.05 was considered statistically significant. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents).

    RESULTS:

    The EBV CF+ group had significantly higher scores for all clinical symptoms. All markers of infection and most immune, neuroendocrine and autonomic markers were similar across the EBV CF+ and EBV CF- group. However, the EBV CF+ group had slightly higher serum C-reactive protein (0.48 vs 0.43 mg/L, p=0.031, high-sensitive assay), total T cell (CD3+) count (median 1573 vs 1481 x 106cells/L, p=0.012), plasma norepinephrine (1420 vs 1113 pmol/L, p=0.01) and plasma epinephrine (363 vs 237 nmol/L, p=0.032); lower low-frequency:high frequency (LF/HF) ratio of heart rate variability at supine rest (0.63 vs 0.76, p=0.008); and an attenuated decline in LF/HF ratio during controlled breathing (-0.11 vs -0.25, p=0.002). Subgrouping according to different CFS diagnostic criteria did not significantly alter the results. Within the EBV CF+ group, there were no strong correlations between clinical symptoms and markers of disease mechanisms. In a multiple regression analysis, serum CRP levels were independently associated with serum cortisol (B= 4.5 x 10-4, p<0.001), urine norepinephrine (B=9.6 x 10-2, p=0.044) and high-frequency power of heart rate variability (B= -3.7 x 10-2, p=0.024).

    CONCLUSIONS:

    In adolescents, CF and CFS 6 months after acute EBV infection are associated with high symptom burden, but no signs of increased viral load and only subtle alterations of immune, autonomic, and neuroendocrine markers of which no one is strongly correlated with symptom scores. A slight sympathetic over parasympathetic predominance is evident in CF and might explain slightly increased CRP levels.
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• Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study

  Forfattere: Maria Pedersen, Tarjei Tørre Asprusten, Kristin Godang, Truls Michael Leegaard, Liv Toril Osnes, Eva Skovlund, Trygve Tjade, Merete Glenne Øie, Vegard Bruun Bratholm Wyller
  Publisert i: Journal of Psychosomatic Research;Available online 10 April 2019

  • Les utdrag

    Objective

    Acute Epstein-Barr virus (EBV) infection is a known trigger of both acute and chronic fatigue. The aim of this study was to investigate associations to fatigue in adolescents with EBV infection during the initial stage and six months after, as well as in healthy controls.

    Methods

    200 adolescents (12–20 years old) with EBV infection were assessed as soon as possible after the onset of symptoms (EBVbaseline) and six months later (EBVsix months, 5 drop-outs). Also, 70 healthy controls (HC) were included. Associations between current fatigue and 148 different variables (including symptoms, functional abilities and biomarkers) were investigated separately for EBVbaseline, EBVsix monthsand HC using linear regression modelling.

    Results

    Fatigue was associated with symptoms of sleeping difficulties, negative emotions, and quality of life under all circumstances. Fatigue was independently associated with markers of immune response at EBVsix months and in HC, not at EBVbaseline. An association between fatigue and markers of autonomic cardiovascular control was only present at EBVsix months. Cognitive functioning shifted from a positive association to fatigue at EBVbaseline to a negative trend at EBVsix months. Markers of infection were not associated with fatigue at EBVbaseline, EBVsix months nor in HC.

    Conclusion

    Irrespective of the cause, fatigue is important for quality of life and is highly associated with negative emotions. Markers of infection and immune response had respectively none and barely any association to fatigue. Autonomic alterations and cognitive dysfunction were exclusively associated with fatigue long after infection, corroborating findings from studies of the Chronic Fatigue Syndrome.

    Keywords

    Adolescents

    Epstein-Barr virus infection

    Fatigue

    Chronic fatigue
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• Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: a prospective cohort study

  Forfattere: MariaPedersen, Tarjei Tørre Asprusten, Kristin Godang, Truls Michael Leegaard, Liv Toril Osnes, Eva Skovlund, Trygve Tjade, Merete Glenne Øie, Vegard Bruun Bratholm Wyller
  Publisert i: Brain, Behavior, and Immunity, Available online 25 September 2018

  • Les utdrag

    Introduction

    Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection.

    Materials and methods

    A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents).

    Results

    In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09 to 1.6]), pain severity (0.2[0.02 to 0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2 to 0.6]), verbal memory (correct word recognition) (1.7[0.1 to 3.3]), plasma C-reactive protein (2.8[1.1 to 4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]).

    Conclusions

    Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes.

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• Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

  Forfattere: Nome RV, Bjøro T, Paus E, Bjerner J, Fosså SD, Steen R, Nustad K, Bolstad N.
  Publisert i: Clin Biochem. 2018 Feb;52:73-79. doi: 10.1016/j.clinbiochem.2017.11.016. Epub 2017 Dec 2.

  • Les utdrag

    BACKGROUND:

    Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay.

    METHODS:

    We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function.

    RESULTS:

    We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels.

    CONCLUSION:

    The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice.

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• Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis.

  Forfattere: Oppen K, Bjerner J, Buchmann M, Piehler AP
  Publisert i: Clin Chem Lab Med. 2017 Jun 27;55(7):e133-e136. doi: 10.1515/cclm-2016-0625.

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• erm gene distribution among Norwegian Bacteroides isolates and evaluation of phenotypic tests to detect inducible clindamycin resistance in Bacteroides species.

  Forfattere: Johnsen BO, Handal N, Meisal R, Bjørnholt JV, Gaustad P, Leegaard TM.
  Publisert i: Anaerobe. 2017 Oct;47:226-232. doi: 10.1016/j.anaerobe.2017.06.004. Epub 2017 Jun 8.

  • Les utdrag
    The aims of this study were to describe the distribution of the most common erm genes in a collection of Norwegian Bacteroides isolates and to investigate whether the phenotypic tests for determining inducible clindamycin resistance among Bacteroides species recommended by EUCAST, NordicAST and the manufacturer of E-test®, are effective. We investigated 175 unique Bacteroides isolates for the presence of erm(B), erm(F) and erm(G) genes, determined their minimum inhibitory concentrations (MICs) to clindamycin and categorised their susceptibility according to EUCAST breakpoints. 27 isolates were resistant to clindamycin. Furthermore, we investigated whether these recommended methods could detect inducible resistance in the Bacteroides isolates: 1) EUCAST recommendation: Dissociated resistance to erythromycin (clindamycin susceptible with erythromycin MIC > 32 mg/L), 2) NordicAST recommendation: Double disk diffusion test (DDD) or 3) Manufacturer of E-test®'s recommendation: prolonged incubation of clindamycin E-test® for 48 h. erm genes were detected in 30 (17%, 95% CI 12%-23%) of 175 Bacteroides isolates with erm(F) as the dominating gene. There were six (4%, 95% CI 1%-7%) of 148 clindamycin susceptible isolates harbouring erm genes, they were considered inducibly resistant to clindamycin. None of the methods for phenotypic detection of inducible clindamycin resistance performed satisfactory with sensitivities of 33%, 17% and 0% and specificities of 90%, 99% and 97% for dissociated resistance, DDD and prolonged incubation of clindamycin E-test®, respectively. In our view, the scientific basis for investigating every Bacteroides isolate for inducible resistance to clindamycin is weak. Molecular detection of erm genes may prove a better option than the phenotypic methods we evaluated.
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• Routine Supercritical Fluid Chromatography Tandem Mass Spectrometry Method for Determination of Vitamin K1 Extracted from Serum with a 96-Well Solid-Phase Extraction Method

  Forfattere: Trude Athammer Sandvik, Asgeir Husa, Marie Buchmann, Elsa Lundanes
  Publisert i: DOI: 10.1373/jalm.2016.021717 Published April 2017

  • Les utdrag

    Background: 

    The concentration of vitamin K1 in serum or plasma is the most common index for assessing vitamin K status. The aim of this study was to develop and validate a rapid and reliable routine method for quantifying vitamin K1 above 0.1 ng/mL. Semi-automation of a simple sample preparation with fast analysis by supercritical fluid chromatography–tandem mass spectrometry (SFC-MS/MS) was exploited.

    Methods: 

    Vitamin K1 was extracted from 250-μL serum samples by the use of protein precipitation and reversed-phase solid-phase extraction (SPE) in 96-well plates and quantified by SFC on a 2.1 × 100 mm Torus 1-Aminoanthracene (1-AA) column in 3.8 min with electrospray ionization—tandem mass spectrometry (MS/MS) detection.

    Results: 

    This method shows good linearity in the concentration range of 0.1–50 ng/mL with a correlation coefficient of R2 >0.999. Imprecision was satisfactory, with repeatability and reproducibility <10% CV. The lower limit of the measuring interval was 0.1 ng/mL, and no systematic bias was observed for the method, which used vitamin K1-d7 as internal standard. Recovery of vitamin K1 in external quality controls was satisfactory compared to other laboratories participating in the external quality assurance scheme. The method is currently in routine use for analysis of serum samples.

    Conclusions: 

    The method allows high-throughput reliable determination of vitamin K1 in serum in the range 0.1–50 ng/mL.

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• Draft Genome Sequences of Candida glabrata Isolates 1A, 1B, 2A, 2B, 3A, and 3B.

  Forfattere: Håvelsrud OE, Gaustad P.
  Publisert i: Genome Announc. 2017 Mar 9;5(10). pii: e00328-16. doi: 10.1128/genomeA.00328-16.

  • Les utdrag
    Here, we report the draft genome sequences of six Candida glabrata isolates. The isolates were taken from blood samples from patients after recurrent C. glabrata infection. Two isolates were taken from each of three patients a minimum 3 months apart.
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• Five-year mortality in patients treated for severe community-acquired pneumonia - a retrospective study.

  Forfattere: Lenz H, Norby GO, Dahl V, Ranheim TE, Haagensen RE.
  Publisert i: Acta Anaesthesiol Scand. 2017 Apr;61(4):418-426. doi: 10.1111/aas.12863. Epub 2017 Feb 5.

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    BACKGROUND:

    The mortality rate in patients with severe community-acquired pneumonia (SCAP) is high. We investigated the 5-year mortality rate and causes of death in a patient population treated for SCAP in our intensive care unit (ICU), and compared the mortality rate in patients with or without chronic obstructive pulmonary disease (COPD) as comorbidity.

    METHODS:

    This retrospective study, which covers a period of 10 years, included patients aged > 18 years admitted to our ICU with SCAP as primary diagnosis and in need of mechanical ventilation for more than 24 h. Data were collected from the ICU internal database and the patients' medical records. The times of death were collected from the Norwegian National Registry, and the causes of death from the Norwegian Cause of Death Registry.

    RESULTS:

    Hundred and seventy three patients were included in the study. The 5-year mortality rate for the total study population was 57.2%. There were no significant differences in the mortality rate between the group with COPD and the group without COPD (61.2% vs. 54.7%, P = 0.43). There was a wide range of comorbidities. The most common were COPD, myocardial infarction and diabetes mellitus. The two main causes of death after discharge were COPD (17 deaths) and cardiovascular diseases (seven deaths).

    CONCLUSIONS:

    The 5-year mortality rate of the study population was high (57.2%). COPD did not seem to be a risk factor for mortality compared to non-COPD patients. The most common causes of death after discharge were COPD and cardiovascular diseases.

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• Microscopy of Stained Urethral Smear in Male Urethritis; Which Cutoff Should be Used?

  Forfattere: Harald Moi, MD, PhD, Usha Hartgill, MD, Kristin Helene Skullerud, MD, Elina J. Reponen, MD, Line Syvertsen, MD, and Amir Moghaddam, PhD
  Publisert i: Sexually Transmitted Diseases: March 2017 - Volume 44 - Issue 3 - p 189–194

  • Les utdrag

    Background: The microscopical diagnosis of male urethritis was recentlyquestioned by Rietmeijer and Mettenbrink, lowering the diagnosticcriteria of the diagnosis to ≥2 polymorphonuclear leucocytes (PMNL)per high power field (HPF), and adopted by Centers for Disease Controland Prevention in their 2015 STD Treatment Guidelines. The EuropeanNon-Gonococcal Urethritis Guideline advocates a limit of ≥5 PMNL/HPF.

    Objective: To determine if syndromic treatment of urethritis should beconsidered with a cutoff value of ≥2 PMNL/HPF in urethral smear.

    Methods: The design was a cross-sectional study investigating the presenceand degree of urethritis relative to specific infections in men attendingan STI clinic as drop-in patients.

    Results: The material included 2 cohorts: a retrospective study of 13,295men and a prospective controlled study including 356 men.We observed amean chlamydia prevalence of 2.3% in the 0–9 stratum, and a 12-foldhigher prevalence (27.3%) in the strata above 9. Of the chlamydia cases,89.8% were diagnosed in strata above 9. For Mycoplasma genitalium, theprevalence was 1.4% in the 0–9 stratum and 11.2% in the stratum ≥10,and 83.6% were diagnosed in strata above 9. For gonorrhea, a significantincrease in the prevalence occurred between the 0–30 strata and >30 stratafrom 0.2% to 20.7%. The results of the prospective study were similar.

    Conclusions: Our data do not support lowering the cutoff to ≥2 PMNL/HPF. However, a standardization of urethral smear microscopy seems to beimpossible. The cutoff value should discriminate between low and highprevalence of chlamydia, mycoplasma, and gonorrhea to include as manyas possible with a specific infection in syndromic treatment, withoutovertreating thosewith few PMNL/HPFand high possibility of having nonspecificor no urethritis.

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• Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial.

  Forfattere: Veum VL, Laupsa-Borge J, Eng Ø, Rostrup E, Larsen TH, Nordrehaug JE, Nygård OK, Sagen JV, Gudbrandsen OA, Dankel SN, Mellgren G.
  Publisert i: Am J Clin Nutr. 2017 Jan;105(1):85-99. doi: 10.3945/ajcn.115.123463.

  • Les utdrag

    Abstract

    BACKGROUND:

    Different aspects of dietary pattern, including macronutrient and food profiles, may affect visceral fat mass and metabolic syndrome.

    OBJECTIVE:

    We hypothesized that consuming energy primarily from carbohydrate or fat in diets with similar food profiles would differentially affect the ability to reverse visceral adiposity and metabolic syndrome.

    DESIGN:

    Forty-six men (aged 30-50 y) with body mass index (in kg/m2) >29 and waist circumference >98 cm were randomly assigned to a very high-fat, low-carbohydrate (VHFLC; 73% of energy fat and 10% of energy carbohydrate) or low-fat, high-carbohydrate (LFHC; 30% of energy fat and 53% of energy carbohydrate) diet for 12 wk. The diets were equal in energy (8750 kJ/d), protein (17% of energy), and food profile, emphasizing low-processed, lower-glycemic foods. Fat mass was quantified with computed tomography imaging.

    RESULTS:

    Recorded intake of carbohydrate and total and saturated fat in the LFHC and VHFLC groups were 51% and 11% of energy, 29% and 71% of energy, and 12% and 34% of energy, respectively, with no difference in protein and polyunsaturated fatty acids. Mean energy intake decreased by 22% and 14% in the LFHC and VHFLC groups. The diets similarly reduced waist circumference (11-13 cm), abdominal subcutaneous fat mass (1650-1850 cm3), visceral fat mass (1350-1650 cm3), and total body weight (11-12 kg). Both groups improved dyslipidemia, with reduced circulating triglycerides, but showed differential responses in total and low-density lipoprotein cholesterol (decreased in LFHC group only), and high-density lipoprotein cholesterol (increased in VHFLC group only). The groups showed similar reductions in insulin, insulin C-peptide, glycated hemoglobin, and homeostasis model assessment of insulin resistance. Notably, improvements in circulating metabolic markers in the VHFLC group mainly were observed first after 8 wk, in contrast to more acute and gradual effects in the LFHC group.

    CONCLUSIONS:

    Consuming energy primarily as carbohydrate or fat for 3 mo did not differentially influence visceral fat and metabolic syndrome in a low-processed, lower-glycemic dietary context. Our data do not support the idea that dietary fat per se promotes ectopic adiposity and cardiometabolic syndrome in humans. This study was registered at clinicaltrials.gov as NCT01750021.

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• Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis.

  Forfattere: Oppen K, Bjerner J, Buchmann M, Piehler AP.
  Publisert i: Clin Chem Lab Med. 2016 Nov 7. pii: /j/cclm.ahead-of-print/cclm-2016-0625/cclm-2016-0625.xml. doi: 10.1515/cclm-2016-0625.

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• Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

  Forfattere: Ebbesen F, Madsen PH, Vandborg PK, Jakobsen LH, Trydal T, Vreman HJ.
  Publisert i: Pediatr Res. 2016 Oct;80(4):511-5. doi: 10.1038/pr.2016.115. Epub 2016 May 25.

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    Abstract

    BACKGROUND:

    Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance.

    MATERIALS:

    Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively.

    RESULTS:

    After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin.

    CONCLUSION:

    Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

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• Urethral inflammatory response to ureaplasma is significantly lower than to Mycoplasma genitalium and Chlamydia trachomatis

  Forfattere: Moi H, Reinton N, Randjelovic I, Reponen EJ, Syvertsen L, Moghaddam A
  Publisert i: Int J STD AIDS. 2016 Aug 24

  • Les utdrag
    A non-syndromic approach to treatment of people with non-gonococcal urethritis (NGU) requires identification of pathogens and understanding of the role of those pathogens in causing disease. The most commonly detected and isolated micro-organisms in the male urethral tract are bacteria belonging to the family of Mycoplasmataceae, in particular Ureaplasma urealyticum and Ureaplasma parvum To better understand the role of these Ureaplasma species in NGU, we have performed a prospective analysis of male patients voluntarily attending a drop in STI clinic in Oslo. Of 362 male patients who were tested for NGU using microscopy of urethral smears, we found the following sexually transmissible micro-organisms: 16% Chlamydia trachomatis, 5% Mycoplasma genitalium, 14% U. urealyticum, 14% U. parvum and 5% Mycoplasma hominis We found a high concordance in detecting in turn U. urealyticum and U. parvum using 16s rRNA gene and ureD gene as targets for nucleic acid amplification testing (NAAT). Whilst there was a strong association between microscopic signs of NGU and C. trachomatis infection, association of M. genitalium and U. urealyticum infections in turn were found only in patients with severe NGU (>30 polymorphonuclear leucocytes, PMNL/high powered fields, HPF). U. parvum was found to colonise a high percentage of patients with no or mild signs of NGU (0-9 PMNL/HPF). We conclude that urethral inflammatory response to ureaplasmas is less severe than to C. trachomatis and M. genitalium in most patients and that testing and treatment of ureaplasma-positive patients should only be considered when other STIs have been ruled out.
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• Incidence and impact on prognosis of peri-procedural myocardial infarction in 2760 elective patients with stable angina pectoris in a historical prospective follow-up study.

  Forfattere: Christensen MK, Huang H, Torp-Pedersen C, Trydal T, Ravkilde J.
  Publisert i: BMC Cardiovasc Disord. 2016 Jun 16;16:140. doi: 10.1186/s12872-016-0293-4.

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    Abstract

    BACKGROUND:

    The clinical significance of myocardial infarction related to treatment with percutaneous coronary intervention (PCI) has been subject of great discussion. This subject has been studied for many years using different definitions of peri-procedural myocardial infarction and different biomarkers, the results have varied greatly depending on methods and time of the study. This study was to determine the incidence and prognostic significance of elevated cardiac biomarkers after elective PCI in patients with stable angina pectoris using the current cut-off set by the Third Universal Definition of Myocardial Infarction and current biomarkers.

    METHODS:

    We performed a historical prospective follow-up study of all patients with stable angina pectoris who underwent elective PCI at Aalborg University Hospital, Denmark from January 1(st) 2000 to December 31(st) 2012. We stratified patients according to peak post-PCI troponin T (cTnT) and Creatine Kinase MB mass (CK-MBmass).

    RESULTS:

    Follow-up for time to all-cause mortality was mean 5.8 years and total 15,891 years and mean 3.7 years and total 10,160 years for the combined endpoint of all-cause mortality and new onset heart failure. During the follow up period 399 of 2760 patients died (14.5 %) and 1095 (39.7 %) suffered the combined endpoint. Post-PCI concentration of cTnT and CK-MBmass was elevated above the defined cut-off in 419 patients (15.2 %) and 113 patients (4.1 %) respectively. There was no statistically significant difference between the groups in stratified analysis of the hazard rates by time regarding all-cause mortality for cTnT nor CK-MBmass. Regarding the combined endpoint the results were ambiguous. The results were unchanged in multivariable analyses that included age and gender.

    CONCLUSION:

    The incidence of elevated biomarkers after elective PCI in patients with stable angina pectoris using the defined cut-off (>5 x URL) was 15.2 % using cTnT and 4.1 % using CK-MBmass. The independent prognostic value for both cardiac biomarkers of any cut-off showed no statistical significance for all-cause mortality, whereas the combined endpoint (all-cause mortality or new-onset heart failure) were ambiguous in both short- and long-term follow-up.

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• Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study.

  Forfattere: Schmedes M, Aadland EK, Sundekilde UK, Jacques H, Lavigne C, Graff IE, Eng Ø, Holthe A, Mellgren G, Young JF, Bertram HC, Liaset B, Clausen MR.
  Publisert i: Mol Nutr Food Res. 2016 Jul;60(7):1661-72. doi: 10.1002/mnfr.201500785. Epub 2016 May 4.

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    Abstract

    SCOPE:

    Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects.

    METHODS:

    In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions.

    RESULTS:

    The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets.

    CONCLUSIONS:

    Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake.

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• Lean Seafood Intake Reduces Postprandial C-peptide and Lactate Concentrations in Healthy Adults in a Randomized Controlled Trial with a Crossover Design.

  Forfattere: Aadland EK, Graff IE, Lavigne C, Eng Ø, Paquette M, Holthe A, Mellgren G, Madsen L, Jacques H, Liaset B.
  Publisert i: J Nutr. 2016 May;146(5):1027-34. doi: 10.3945/jn.115.229278. Epub 2016 Apr 20.

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    Abstract

    BACKGROUND:

    Recently we showed that lean seafood consumption reduced circulating triacylglycerol (TG) and VLDL concentrations and prevented an elevated total-to-HDL-cholesterol ratio relative to intake of a nonseafood diet.

    OBJECTIVE:

    We aimed to elucidate whether diet-induced altered carbohydrate metabolism could be a contributing factor to the previously observed different lipoprotein patterns.

    METHODS:

    This was a secondary outcome and explorative randomized controlled trial with a crossover design in 20 healthy adults (7 men and 13 women) that were 50.6 ± 3.4 (mean ± SEM) y old, weighed 75.7 ± 2.5 kg, and had a body mass index (BMI, in kg/m(2)) of 25.6 ± 0.7. After a 3-wk run-in period and separated by a 5-wk wash-out period, the participants consumed 2 balanced diets [in percentage of energy (energy%); 29% fat, 52% carbohydrates, 19% protein] for 4 wk. The diets varied in the main protein sources; 60 energy% of total protein was from either lean seafood or nonseafood sources. On the first and last day of each diet period, fasting and postprandial blood samples were collected before and after consumption of test meals (in energy%; 28% fat, 52% carbohydrates, 20% protein) with cod or lean beef.

    RESULTS:

    The diets did not alter serum insulin and glucose concentrations. However, relative to the nonseafood diet period, the lean seafood diet period reduced postprandial C-peptide (P = 0.04) and lactate (P = 0.012) concentrations and fasting and postprandial TG/HDL-cholesterol ratios (P = 0.002). Hence, different postprandial lactate levels occurred at equal glucose concentrations.

    CONCLUSIONS:

    Even though the diets did not alter serum insulin and glucose concentrations, intake of the lean seafood compared with the nonseafood diet reduced postprandial concentrations of C-peptide and lactate and the TG/HDL-cholesterol ratio in healthy adults in a manner that may affect the long-term development of insulin resistance, type 2 diabetes, and cardiovascular disease. This trial was registered at www.clinicaltrials.gov as NCT01708681.

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• Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates.

  Forfattere: Andersen KM, Kristoffersen AK, Ingebretsen A, Vikholt KJ, Örtengren UT, Olsen I, Enersen M, Gaustad P.
  Publisert i: J Oral Microbiol. 2016 Feb 8;8:29849. doi: 10.3402/jom.v8.29849.

  • Les utdrag

    Abstract

    BACKGROUND:

    Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections.

    OBJECTIVES:

    To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK(®)2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility.

    DESIGN:

    A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK(®)2) and mass spectrometry (MALDI-TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests(®).

    RESULTS:

    Using VITEK(®)2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L.

    CONCLUSIONS:

    Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high MICs to fluconazole and flucytosine. MALDI-TOF was more definitive than VITEK(®)2 for C. glabrata identification.

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• Effect of phototherapy with turquoise vs. blue LED light of equal irradiance in jaundiced neonates.

  Forfattere: Ebbesen F, Vandborg PK, Madsen PH, Trydal T, Jakobsen LH, Vreman HJ.
  Publisert i: Pediatr Res. 2016 Feb;79(2):308-12. doi: 10.1038/pr.2015.209. Epub 2015 Oct 20.

  • Les utdrag

    Abstract

    BACKGROUND:

    Blue light with peak emission around 460 nm is the preferred treatment of neonatal hyperbilirubinemia. However, studies using fluorescent light tubes have suggested that turquoise light with peak emission at 490 nm may be more efficient. At present, the predominant light source for phototherapy is light emitting diodes (LEDs). Hence, the aim of this study was to compare the bilirubin-reducing effect in jaundiced neonates treated either with turquoise or with blue LED light with peak emission at 497 or 459 nm, respectively, with equal irradiance on the infants.

    METHODS:

    Infants with gestational age ≥33 wk and uncomplicated hyperbilirubinemia were randomized to either turquoise or blue LED light and were treated for 24 h. The mean irradiance footprint at skin level was 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively.

    RESULTS:

    Forty-six infants received turquoise light and 45 received blue light. The median (95% confidence interval) decrease of total serum bilirubin was 35.3% (32.5; 37.3) and 33.1% (27.1; 36.8) for infants treated with turquoise and blue lights, respectively. The difference was nonsignificant (P = 0.53). The decrease was positively correlated to postnatal age and negatively to birth weight.

    CONCLUSION:

    Using LED light of equal irradiance, turquoise and blue lights had equal bilirubin-reducing effect on hyperbilirubinemia of neonates.

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• Functional analysis of an unusual type IV pilus in the Gram-positive Streptococcus sanguinis.

  Forfattere: Gurung I, Spielman I, Davies MR, Lala R, Gaustad P, Biais N, Pelicic V.
  Publisert i: Mol Microbiol. 2016 Jan;99(2):380-92. doi: 10.1111/mmi.13237.

  • Les utdrag

    Abstract

    Type IV pili (Tfp), which have been studied extensively in a few Gram-negative species, are the paradigm of a group of widespread and functionally versatile nano-machines. Here, we performed the most detailed molecular characterisation of Tfp in a Gram-positive bacterium. We demonstrate that the naturally competent Streptococcus sanguinis produces retractable Tfp, which like their Gram-negative counterparts can generate hundreds of piconewton of tensile force and promote intense surface-associated motility. Tfp power 'train-like' directional motion parallel to the long axis of chains of cells, leading to spreading zones around bacteria grown on plates. However, S. sanguinis Tfp are not involved in DNA uptake, which is mediated by a related but distinct nano-machine, and are unusual because they are composed of two pilins in comparable amounts, rather than one as normally seen. Whole genome sequencing identified a locus encoding all the genes involved in Tfp biology in S. sanguinis. A systematic mutational analysis revealed that Tfp biogenesis in S. sanguinis relies on a more basic machinery (only 10 components) than in Gram-negative species and that a small subset of four proteins dispensable for pilus biogenesis are essential for motility. Intriguingly, one of the piliated mutants that does not exhibit spreading retains microscopic motility but moves sideways, which suggests that the corresponding protein controls motion directionality. Besides establishing S. sanguinis as a useful new model for studying Tfp biology, these findings have important implications for our understanding of these widespread filamentous nano-machines.

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• In vitro element release and biological aspects of base–metal alloys for metal-ceramic applications

  Forfattere: Charlotta Holm, Else Morisbak, Torill Kalfoss og Jon E. Dahl
  Publisert i: Acta Biomaterialia Odontologica Scandinavica 12/2015; 1(2-4):70-75.

  • Les utdrag
    Objective: The aims of this study were to investigate the release of element from, and the biological response in vitro to, cobalt–chromium alloys and other base–metal alloys used for the fabrication of metal-ceramic restorations.Material and methods: Eighteen different alloys were investigated. Nine cobalt–chromium alloys, three nickel–chromium alloys, two cobalt–chromium–iron alloys, one palladium–silver alloy, one high-noble gold alloy, titanium grade II and one type III copper–aluminium alloy. Pure copper served as positive control. The specimens were prepared according to the ISO standards for biological and corrosion testing. Passive leaching of elements was measured by using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) after incubation in cell culture media, MEM, for 3 days. Corrosion testing was carried out in 0.9% sodium chloride (NaCl) and 1% lactic acid for 7 days, and the element release was measured by Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES). The biological response from the extract solutions was measured though MTT cytotoxicity testing and the Hen's egg test-chorio-allantoic membrane (HET-CAM) technique for irritationt.Results: The corrosion test showed similar element release from base-metal alloys compared to noble alloys such as gold. Apart from the high-copper alloy, all alloys expressed low element release in the immersion test, no cytotoxic effect in the MTT test, and were rated non-irritant in the HET-CAM test.Conclusions: Minimal biological response was observed for all the alloys tested, with the exception of the high-copper alloy. 
    In vitro element release and biological aspects of base–metal alloys for metal-ceramic applications. Available from: https://www.researchgate.net/publication/282483253_In_vitro_element_release_and_biological_aspects_of_base-metal_alloys_for_metal-ceramic_applications [accessed Feb 22, 2016].
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• Hemophagocytic lymphohistiocytosis in leprosy.

  Forfattere: Høyvoll LR, Fløisand Y, Orrem HL, Gunnarsson R, Landrø L, Brevig T, Gaustad P, Nordøy I.
  Publisert i: Lepr Rev. 2015 Dec;86(4):403-6.

  • Les utdrag

    Abstract

    A patient from Southeast Asia was diagnosed with systemic lupus erythematosus. One year later, she experienced exacerbation of skin lesions and was diagnosed with erythema nodosum leprosum. Upon treatment, the patient developed hemophagocytic lymphohistiocytosis with multi-organ failure and died from invasive fungal infection. Hemophagocytic lymphohistiocytosis has to our knowledge, not previously been reported in leprosy.

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• Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors

  Forfattere: Sprauten M, Haugnes HS, Brydøy M, Kiserud C, Tandstad T, Bjøro T, Bjerner J, Cvancarova M, Fosså SD, Oldenburg J.
  Publisert i: Ann Oncol. 2015 Oct;26(10):2133-40.

  • Les utdrag

    Abstract

    BACKGROUND:

    Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment.

    PATIENTS AND METHODS:

    Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression.

    RESULTS:

    Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively.

    CONCLUSIONS:

    The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important.

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• Twenty-two years of candidaemia surveillance: results from a Norwegian national study.

  Forfattere: Hesstvedt L, Gaustad P, Andersen CT, Haarr E, Hannula R, Haukland HH, Hermansen NO, Larssen KW, Mylvaganam H, Ranheim TE, Sandven P, Nordøy I; Norwegian Yeast Study Group., Kanestrøm A, Grub C, Onken A, Thielsen C, Skaare D, Tofteland S, Sønsteby LJ, Hjet
  Publisert i: Clin Microbiol Infect. 2015 Oct;21(10):938-45. doi: 10.1016/j.cmi.2015.06.008.

  • Les utdrag

    Abstract

    Several studies have reported an increased incidence of candidaemia and a redistribution of species, with a decrease in the number of Candida albicans isolates. In Norway, a prospective, national surveillance study of candidaemia has been ongoing since 1991. Data from the period 1991-2003 have been published previously. The aim of this study was to follow up the incidence, species distribution and antifungal susceptibility of Candida species isolates from blood cultures in the period 2004-2012, and compare them with the corresponding findings from the period 1991-2003. Blood culture isolates of Candida species from all medical microbiological laboratories in Norway were identified and susceptibility tested at the Norwegian Mycological Reference Laboratory. A total of 1724 isolates were recovered from 1653 patients in the period 2004-2012. Comparison of the two periods showed that the average incidence of candidaemia episodes per 100 000 inhabitants increased from 2.4 (1991-2003) to 3.9 (2004-2012). The increase in incidence in the latter period was significantly higher in patients aged >40 years (p 0.001), and a marked increase was observed in patients aged >60 years (p < 0.001). In conclusion, the average incidence in Norway over a period of 22 years modestly increased from 2.4 to 3.9 per 100,000 inhabitants, this being mainly accounted for by candidaemia in the elderly. The species distribution was stable, and the rate of acquired resistance was low.

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• Interference of common haemoglobin variants with the Tosoh G7 standard mode HbA1c method

  Forfattere: Piehler AP, Grimholt RM, Bjerner J, Buchmann MS.
  Publisert i: Scand J Clin Lab Invest. 2015 Sep;75(5):362-6.

  • Les utdrag

    Abstract

    BACKGROUND:

    HbA1c methods may be prone to interference by the presence of haemoglobin variants. In contrast to the variant mode of the HbA1c method on the Tosoh G7 instrument, the literature lacks investigations of haemoglobin variant interference with the standard mode. The current study sought to investigate whether different haemoglobin variants interfere with the Tosoh G7 standard mode HbA1c method, and whether present haemoglobin variants are identifiable on respective chromatograms.

    METHODS:

    Samples routinely analyzed for HbA1c and suspected of having haemoglobin variants (N = 103) were included. HbA1c was measured on a Tosoh G7 in standard mode (Tosoh Corporation, Japan), and on the DCA Vantage (Siemens, Germany). Haemoglobin variants were identified using the VARIANT(™)β-Thalassemia Short Program (Bio-Rad Laboratories, Hercules, CA, USA) and by DNA sequencing.

    RESULTS:

    The Tosoh G7 in standard mode measured significantly lower HbA1c results (between 1.0 and 2.5 percentage points absolute bias corresponding to between 11 and 27 mmol/mol, p < 0.001) in samples in which common haemoglobin variants (HbS, HbC, HbD or HbE) were present (n = 61). No significant difference in HbA1c (0.04 percentage points, p = 0.74) was found between Tosoh G7 standard mode and DCA Vantage in samples in which haemoglobin variants were absent (n = 36). In contrast to HbS and HbD, HbE and HbC trait could be identified on respective chromatograms.

    CONCLUSION:

    The presence of common haemoglobin variants results in falsely low HbA1c measurements on the Tosoh G7 in standard mode. HbS and HbD trait are not identifiable on respective haemoglobin chromatograms.

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• Identification of macrolide-resistant Mycoplasma genitalium using real-time PCR

  Forfattere: Wold C, Sorthe J, Hartgill U, Olsen AO, Moghaddam A, Reinton N.
  Publisert i: J Eur Acad Dermatol Venereol. 2015 Aug;29(8):1616-20.

  • Les utdrag

    Abstract

    OBJECTIVES:

    Mycoplasma genitalium is a common cause of non-gonococcal urethritis (NGU) in Western Europe, but is not routinely tested for in all clinics. A high prevalence of macrolide-resistant M. genitalium has been reported. An easy to use test that can predict likely macrolide treatment failure is potentially very valuable. We report the development of a rapid and reliable real-time PCR-assay which detects all relevant resistance loci in the M. genitalium 23S rRNA gene.

    METHODS:

    Mycoplasma genitalium-positive clinical samples were collected between December 2012 and May 2013, from samples sent routinely to the laboratory for diagnostic testing for M. genitalium. The real-time PCR assay was designed using forward amplification primers complementary to all relevant commonly identified 23s rRNA gene mutations, a common reverse amplification primer and a common TaqMan Probe.

    RESULT:

    We report a Taqman assay for detection of common 23S rRNA genotypes at position 2058 and 2059 (Escherichia coli numbering) associated with macrolide resistance, directly from clinical samples. We validated the assay by comparison with DNA sequence determination.

    CONCLUSION:

    Our TaqMan assay detects common genotypes associated with macrolide-resistant M. genitalium, namely, A2058G, A2059G and A2058C. We show association between the presence of resistant M. genitalium and treatment failure, thereby confirming the validity of testing for these mutants to prevent further spread of antimicrobial resistance and to allow informed choice of antibiotics for treatment.

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• Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study.

  Forfattere: Berents TL, Carlsen KC, Mowinckel P, Skjerven HO, Kvenshagen B, Rolfsjord LB, Bradley M, Lieden A, Carlsen KH, Gaustad P, Gjersvik P.
  Publisert i: PLoS One. 2015 Jun 12;10(6):e0130145. doi: 10.1371/journal.pone.0130145.

  • Les utdrag

    Abstract

    Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants. 

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• Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

  Forfattere: van der Linden JW, Arendrup MC, Warris A, Lagrou K, Pelloux H, Hauser PM, Chryssanthou E, Mellado E, Kidd SE, Tortorano AM, Dannaoui E, Gaustad P, Baddley JW, Uekötter A, Lass-Flörl C, Klimko N, Moore CB, Denning DW, Pasqualotto AC, Kibbler C, Arikan-Akda
  Publisert i: Emerg Infect Dis. 2015 Jun;21(6):1041-4. doi: 10.3201/eid2106.140717.

  • Les utdrag

    Abstract

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. 

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• Copy number variation in the ATP-binding cassette transporter ABCC6 gene and ABCC6 pseudogenes in patients with pseudoxanthoma elasticum

  Forfattere: Kringen MK, Stormo C, Berg JP, Terry SF, Vocke CM, Rizvi S, Hendig D, Piehler AP.
  Publisert i: Mol Genet Genomic Med. 2015 May;3(3):233-7.

  • Les utdrag

    Abstract

    Single mutations in the ATP-binding cassette transporter (ABCC6) gene (OMIM 603234) are known to cause the rare autosomal recessive disease pseudoxanthoma elasticum (PXE). Recently, we have found that copy number variations (CNVs) in pseudogenes of the ABCC6 gene are quite common. The aim of this study was to investigate the frequency and possible contribution of CNV in ABCC6 and its pseudogenes in PXE. Genomic DNA from 212 PXE individuals were examined for copy number by pyrosequencing and quantitative polymerase chain reaction (PCR) and compared with healthy individuals. The frequency of PXE individuals with any CNV was higher than in healthy individuals. The majority of variation comprised known and possibly new deletions in the ABCC6 gene and duplications of the ABCC6P1 and ABCC6P2 genes. ABCC6 deletions and ABCC6P2 duplications were not observed in 142 healthy individuals. In conclusion, by pyrosequencing and quantitative PCR, we were able to detect known and possibly new deletions in the ABCC6 gene that may have caused the PXE phenotype. Pyrosequencing may be used in PXE patients who have obtained incomplete genotype from conventional techniques. The frequency of ABCC6P2 pseudogene duplication was more common in PXE patients than healthy individuals and may affect the PXE phenotype.

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• Topical treatment with fresh human milk versus emollient on atopic eczema spots in young children: a small, randomized, split body, controlled, blinded pilot study.

  Forfattere: Berents TL, Rønnevig J, Søyland E, Gaustad P, Nylander G, Løland BF.
  Publisert i: BMC Dermatol. 2015 May 4;15:7. doi: 10.1186/s12895-015-0027-9.

  • Les utdrag

    BACKGROUND:

    Public health nurses report on effects of fresh human milk as treatment for conjunctivitis, rhinitis and atopic eczema (AE), the latter being highly prevalent in early childhood. Emollients and topical corticosteroids are first line treatment of AE. As many caregivers have steroid phobia, alternative treatment options for mild AE are of interest. The aim of this small pilot study was to assess the potential effects and risks of applying fresh human milk locally on eczema spots in children with AE.

    METHODS:

    This was a split body, controlled, randomized and physician blinded pilot study, of children with AE with two similar contralateral eczema spots having a mother breastfeeding the child or a sibling. Fresh expressed milk and emollient was applied on the intervention spot and emollient alone on the control area, three times a day for four weeks. The severity and area of the eczema spots was evaluated weekly, and samples from milk and the spots were analysed weekly with respect to bacterial colonisation.

    RESULTS:

    Of nine patients included, six completed the study. Mean age at inclusion was 18.5 months. The spots examined were localized on the arms, legs or cheeks. The spots were similar in severity, but differed in area. In one patient the eczema ceased after inclusion. In four patients both control and intervention areas increased during the intervention. The relative change in eczema area compared to baseline showed less increase in the intervention spots in two patients, whereas the opposite was observed in three. In four children Staphylococcus aureus was found in their eczema once or more. In three of the 28 human milk samples, Staphylococcus aureus, alfa haemolytic streptococci or coagulase negative staphylococci were detected. Staphylococcus aureus was found once both in human milk and in the eczema spots, no clinical signs of infection were however observed. No secondary infection due to milk application was detected.

    CONCLUSION:

    In this small pilot study, no effect was found on eczema spots treated with topical application of fresh human milk. (ClinicalTrials.gov Identifier, NCT02381028 ).

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• Six-day stability of erythrocyte and reticulocyte parameters in-vitro: a comparison of blood samples from healthy, iron-deficient, and thalassemic individuals

  Forfattere: Sudmann-Day ÅA, Piehler A, Klingenberg O, Urdal P.
  Publisert i: Scand J Clin Lab Invest. 2015 May;75(3):247-53.

  • Les utdrag

    Abstract

    INTRODUCTION:

    Stability for up to 6 days' storage of erythrocyte and reticulocyte parameters in samples from iron-deficient and thalassemic individuals has not yet been reported. This lack of knowledge challenges evaluation of the full blood count in referral samples for hemoglobinopathy evaluation. We therefore hereby present such sample stability data.

    METHODS:

    We included fresh (less than 4 hours old) blood samples from eight healthy, eight iron-deficient, and 11 thalassemic individuals. A full blood count, including reticulocyte parameters, was performed on a Sysmex XE-2100 once daily during a 6-day storage period at room temperature. For healthy individuals, we also studied stability of refrigerated samples and investigated analytical and biological variation.

    RESULTS:

    Hemoglobin concentration, erythrocyte count, and mean corpuscular hemoglobin were stable for 6 days in all diagnostic groups. Mean corpuscular volume increased less in samples from iron-deficient individuals while the number of reticulocytes increased more in samples from thalassemic, as compared to healthy individuals. Ret-He stability depended on its baseline value. Within-person biological variation in samples from healthy individuals was low both for erythrocyte parameters and for reticulocyte hemoglobin, while higher for reticulocyte counts.

    CONCLUSION:

    Results for hemoglobin concentration, erythrocyte count, and mean corpuscular hemoglobin are reliable in hemoglobinopathy investigation of referred samples for up to 6 days. Storage time-dependent changes of other erythrocyte and reticulocyte parameters in blood samples from iron-deficient and thalassemic individuals differ from those of healthy individuals.

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• Corynebacterium pseudotuberculosis Pneumonia in a Veterinary Student Infected During Laboratory Work.

  Forfattere: Heggelund L, Gaustad P, Håvelsrud OE, Blom J, Borgen L, Sundset A, Sørum H, Frøland SS.
  Publisert i: Open Forum Infect Dis. 2015 Apr 15;2(2):ofv053. doi: 10.1093/ofid/ofv053.

  • Les utdrag

    Abstract

    We present a case of Corynebacterium pseudotuberculosis pneumonia in a veterinary student, with molecular genetic evidence of acquisition during laboratory work, an observation relevant for laboratory personnel working with C pseudotuberculosis isolates. The patient was clinically cured with 14 months trimethoprim/sulfamethoxazole and rifampicin combination treatment. 

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• Development of DinQ from Escherichia coli as an anti-cell-envelope antibiotic

  Forfattere: Booth JA, Suganthan R, Gaustad P, Bjørås M.
  Publisert i: Int J Antimicrob Agents. 2015 Feb;45(2):196-7. doi: 10.1016/j.ijantimicag.2014.10.005.

  • Les utdrag
    The increasing prevalence of antibiotic-resistant bacterial infections together with a lack of new classes of antibiotics requires a search for new antimicrobial agents from unique sources. The need is particularly acute for Gram-negative infections, as highlighted by several recent reports. We have previously published a characterisation of the LexA-sensitive dinQ gene and agrB sRNA from Escherichia coli. One of the defining phenotypes of DinQ was that modest overexpression led to a greatly increased sensitivity to DNA damage, and ectopic expression was highly lethal [1].
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• RNA-sequencing analysis of HepG2 cells treated with atorvastatin

  Forfattere: Stormo C, Kringen MK, Lyle R, Olstad OK, Sachse D, Berg JP, Piehler AP.
  Publisert i: PLoS One. 2014 Aug 25;9(8):e105836.

  • Les utdrag

    Abstract

    The cholesterol-lowering drug atorvastatin is among the most prescribed drug in the world. Alternative splicing in a number of genes has been reported to be associated with variable statin response. RNA-seq has proven to be a powerful technique for genome-wide splice variant analysis. In the present study, we sought to investigate atorvastatin responsive splice variants in HepG2 cells using RNA-seq analysis to identify novel candidate genes implicated in cholesterol homeostasis and in the statin response. HepG2 cells were treated with 10 µM atorvastatin for 24 hours. RNA-seq and exon array analyses were performed. The validation of selected genes was performed using Taqman gene expression assays. RNA-seq analysis identified 121 genes and 98 specific splice variants, of which four were minor splice variants to be differentially expressed, 11 were genes with potential changes in their splicing patterns (SYCP3, ZNF195, ZNF674, MYD88, WHSC1, KIF16B, ZNF92, AGER, FCHO1, SLC6A12 and AKAP9), and one was a gene (RAP1GAP) with differential promoter usage. The IL21R transcript was detected to be differentially expressed via RNA-seq and RT-qPCR, but not in the exon array. In conclusion, several novel candidate genes that are affected by atorvastatin treatment were identified in this study. Further studies are needed to determine the biological significance of the atorvastatin responsive splice variants that have been uniquely identified using RNA-seq.

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• Serum bilirubin concentration in healthy adult North-Europeans is strictly controlled by the UGT1A1 TA-repeat variants

  Forfattere: Kringen MK, Piehler AP, Grimholt RM, Opdal MS, Haug KB, Urdal P.
  Publisert i: PLoS One. 2014 Feb 28;9(2):e90248.

  • Les utdrag

    Abstract

    The major enzyme responsible for the glucuronidation of bilirubin is the uridine 5'-diphosphoglucose glucuronosyltransferase A1 (UGT1A1) enzyme, and genetic variation in the UGT1A1 gene is reported to influence the bilirubin concentration in the blood. In this study, we have investigated which gene-/haplotype variants may be useful for genetic testing of Gilbert's syndrome. Two groups of samples based on serum bilirubin concentrations were obtained from the Nordic Reference Interval Project Bio-bank and Database (NOBIDA): the 150 individuals with the highest bilirubin (>17.5 µmol/L) and the 150 individuals with normal bilirubin concentrations (<17.5 µmol/L). The individuals were examined for the TA6>TA7 variant in the UGT1A1 promoter and 7 tag-SNPs in an extended promoter region of UGT1A1 (haplotype analysis) and in selected SNPs in candidate genes (SLCO1B3, ABCC2 and NUP153). We found significant odds ratios for high bilirubin level for all the selected UGT1A1 variants. However, in stepwise multivariate logistic regression analysis of all genetic variants together with age, sex, country of origin and fasting time, the repeat variants of UGT1A1 TA6>TA7 and SLCO1B3 rs2117032 T>C were the only variants significantly associated with higher bilirubin concentrations. Most individuals with high bilirubin levels were homozygous for the TA7-repeat (74%) while only 3% were homozygous for the TA7-repeat in individuals with normal bilirubin levels. Among individuals heterozygous for the TA7-repeat, a low frequent UGT1A1-diplotype harboring the rs7564935 G-variant was associated with higher bilirubin levels. In conclusion, our results demonstrate that in testing for Gilbert's syndrome, analyzing for the homozygous TA7/TA7-genotype would be appropriate.

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• Rapid and reliable detection of α-globin copy number variations by quantitative real-time PCR

  Forfattere: Grimholt RM, Urdal P, Klingenberg O, Piehler AP.
  Publisert i: BMC Hematol. 2014 Jan 24;14(1):4.

  • Les utdrag

    Abstract

    BACKGROUND:

    Alpha-thalassemia is the most common human genetic disease worldwide. Copy number variations in the form of deletions of α-globin genes lead to α-thalassemia while duplications of α-globin genes can cause a severe phenotype in β-thalassemia carriers due to accentuation of globin chain imbalance. It is important to have simple and reliable methods to identify unknown or rare deletions and duplications in cases in which thalassemia is suspected but cannot be confirmed by multiplex gap-PCR. Here we describe a copy number variation assay to detect deletions and duplications in the α-globin gene cluster (HBA-CNV).

    RESULTS:

    Quantitative real-time PCR was performed using four TaqMan® assays which specifically amplify target sequences representing both the α-globin genes, the -α3.7 deletion and the HS-40 region. The copy number for each target was determined by the 2-ΔΔCq method. To validate our method, we compared the HBA-CNV method with traditional gap-PCR in 108 samples from patients referred to our laboratory for hemoglobinopathy evaluation. To determine the robustness of the four assays, we analyzed samples with and without deletions diluted to obtain different DNA concentrations. The HBA-CNV method identified the correct copy numbers in all 108 samples. All four assays showed the correct copy number within a wide range of DNA concentrations (3.2-100 ng/μL), showing that it is a robust and reliable method. By using the method in routine diagnostics of hemoglobinopathies we have also identified several deletions and duplications that are not detected with conventional gap-PCR.

    CONCLUSIONS:

    HBA-CNV is able to detect all known large deletions and duplications affecting the α-globin genes, providing a flexible and simple workflow with rapid and reliable results.

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• Hb Ullevaal [β78(EF2)Leu→Val; HBB: c.235C>G], a new hemoglobin variant interfering with Hb A1c measurement using a cation exchange high performance liquid chromatography method.

  Forfattere: Grimholt RM, Sudmann ÅA, Piehler AP, Urdal P, Klingenberg O.
  Publisert i: Hemoglobin. 2014;38(2):130-2.

  • Les utdrag

    Abstract

    A new hemoglobin (Hb) variant was detected during Hb A1c measurement. DNA sequencing showed heterozygosity for the single nucleotide substitution (C > G) on the β-globin gene causing an amino acid change [β78(EF2)Leu→Val; HBB: c.235C > G]. The new Hb variant was designated Hb Ullevaal after the hospital at which it was discovered. Heterozygosity for Hb Ullevaal appears to have no clinical significance. However, it interferes with Hb A1c measurement by cation exchange high performance liquid chromatography (HPLC), causing falsely low Hb A1c concentration when using the Tosoh G7 apparatus in variant mode.

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• Medisinsk mikrobiologi og infeksjonssykdommer.

  Forfattere: Trygve Tjade
  Publisert i: Fagbokforlaget. 4. utgave 2013 ISBN 978-82-450-1497-6.

  • Les utdrag

    Vi har gode metoder for å forebygge, påvise og behandle infeksjonssykdommer. Likevel er disse sykdommene et stort helseproblem; de er svært vanlige, og de er smittsomme. I 4. utgave av Medisinsk mikrobiologi og infeksjonssykdommer blir kunnskap om infeksjonssykdommer knyttet til mikroorganismene som forårsaker dem.

    Medisinsk mikrobiologi og infeksjonssykdommer er egnet for studenter og yrkesaktive innenfor alle helseprofesjonene.

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• Longitudinal serum testosterone, LH and FSH levels in a population-based sample of long-term testicular cancer survivors.

  Forfattere: Mette Sprauten, Marianne Brydøy, Hege Sagstuen Haugnes, Milada Cvancarova, Trine Bjøro, Johan Bjerner, Sophie Dorothea Fosså, and Jan Oldenburg
  Publisert i: Journal of Clinical Oncology

  • Les utdrag

    Purpose: To assess longitudinal long-term alterations of testosterone (T), LH, and FSH intesticular cancer survivors (TCSs).

    Methods: In all, 307 TCSs treated from 1980-1994 provided blood samples after orchiectomybut before further treatment, at Survey I (SI) (1998-2002), and Survey II (SII) (2007-2008).Levels of sex hormones were categorized according to quartiles and reference range (2.5- and 97.5 percentiles) of 599 controls for each decadal age group. TCSs were categorizedaccording to treatment; surgery (S), radiotherapy (RT) or chemotherapy (CT). The risk ofhigher (LH) or lower (T) levels was assessed with Chi-square test (FSH) or ordinal logisticregression analysis, and expressed as odds ratios (ORs) with 95% Confidence Interval (CI).

    Results: Risk of lower T and higher LH and FSH levels was significantly increased for TCSsat all time points after RT or CT. At SII, ORs for lower T categories were 3.3 (95%CI; 2.3–4.7) and 5.2 (95%CI; 3.5– 7.9) for RT and CT respectively. ORs for increased LH and FSHwere: 4.4 (95%CI; 3.1-6.5) and 18.9 (95%CI; 11.0-32.6), respectively (RT), and 3.6 (95%CI;2.4-5.3) and 14.2 (95%CI; 8.3-24.4), respectively (CT). The cumulative platinum dose wassignificantly associated with risk of higher LH levels at both surveys and FSH at SI. In total,half of TCSs had at least one out of three sex hormone levels outside the reference range atSII.

    Conclusion: Long-term TCSs are at risk of premature hormonal ageing. Our findings maypertain to cancer survivors in general, underlining the importance of extended follow-up.

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• Vitamin D deficiency in alcohol-use disorders and its relationship to comorbid major depression: A cross-sectional study of inpatients in Nepal.

  Forfattere: Neupane SP, Lien L, Hilberg T, Bramness JG.
  Publisert i: Drug Alcohol Depend. 2013 Dec 1;133(2):480-5.

  • Les utdrag

    BACKGROUND: Mounting evidence suggests that deficiency of vitamin D may be associated with major health problems, including alcohol-use disorders (AUD) and major depression (MD). This study aimed to identify the vitamin D status of Nepalese inpatients with an AUD. We explored socio-demographic and alcohol-use related correlates and the relationship between vitamin D deficiency and comorbid MD.

    METHODS: A cross-sectional study was conducted on AUD inpatients (N=174) at eight alcohol/drug treatment centres around Kathmandu. Structured questionnaires were administered to assess the socio-demographic and alcohol-use parameters and to establish DSM-IV diagnoses of AUD and MD. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) concentration of <50nmol/L.

    RESULTS: The prevalence of vitamin D deficiency was 64%. Higher age, having a stable job or business, shorter time since last alcohol intake and winter serum samples were related to having lower 25(OH)D levels. Several features of AUD severity were associated with low vitamin D levels: guilt about drinking, using alcohol as eye-opener, and history of relapse after alcohol treatment (p≤0.03). Patients with a comorbid major depression, in particular secondarily depressed cases, were less likely to have vitamin D deficiency (X(2)=6.8; p=0.01).

    CONCLUSIONS: This study confirms high rates of vitamin D deficiency in alcohol treatment sample and shows a positive association between vitamin D deficiency and severity of alcohol-use disorders. Competing risk and other confounders may help explain the vitamin D status among patients with alcohol-use disorders and comorbid major depression.

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• Varsling av sterkt avvikende analyseresultater til rekvirenter utenfor sykehus

  Forfattere: Aakre KM, Hov GG, Skadberg O, Piehler A, Distante S, Hager HB.
  Publisert i: Tidsskr Nor Laegeforen. 2013 Nov 12;133(21):E1-E6.

  • Les utdrag

    BAKGRUNN: Når laboratoriet påviser analyseresultater som kan medføre alvorlig helsefare for pasienten, skal behandlingsansvarlig lege varsles. Det er per i dag ingen enighet om når et prøvesvar er så avvikende at varsling bør gjøres.

    MATERIALE OG METODE: En arbeidsgruppe i regi av Norsk selskap for medisinsk biokjemi innhentet oversikt over hvilke varslingsgrenser som blir brukt ved norske laboratorier samt i internasjonal litteratur, og foretok en spørreundersøkelse blant allmennpraktikere som rekvirerte analyser fra seks norske laboratorier. Det ble utført litteratursøk for å innhente kunnskapsbasert informasjon om når et analyseresultat medfører akutt livsfare. Konsekvenser for ressursbruk ved bruk av ulike grenser ble estimert på bakgrunn av analyseresultater fra en 6 måneders periode fra et større norsk sykehuslaboratorium.

    RESULTATER: Hvilke grenser som brukes nasjonalt og internasjonalt varierer, men medianverdiene for disse er relativt sammenfallende. Allmennpraktikerne ønsket at en del analyser skulle varsles, hovedsakelig elektrolytter og hematologiske parametre. De varslingsgrensene allmennpraktikerne foreslo var gjennomgående mindre avvikende sammenlignet med de som ble brukt av laboratoriene (medianverdier). Hvilke grenser som brukes har stor betydning for hvor mye ressurser laboratoriene vil bruke på varsling av laboratorieresultater.

    FORTOLKING: Laboratorier og allmennleger har ulike oppfatninger av hva som bør være varslingsgrenser for medisinsk biokjemiske analyseresultater hos voksne. Anbefalingen fra arbeidsgruppen må oppfattes som veiledende.

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• UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone.

  Forfattere: Stormo C, Bogsrud MP, Hermann M, Åsberg A, Piehler AP, Retterstøl K, Kringen MK
  Publisert i: Mol Diagn Ther. 2013 Aug;17(4):233-7.

  • Les utdrag

    BACKGROUND: Atorvastatin is commonly used to reduce cholesterol. Atorvastatin acid is converted to its corresponding lactone form spontaneously or via glucuronidation mediated by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A3. Atorvastatin lactone is pharmacologically inactive, but is suspected to be muscle toxic and cause statin-induced myopathy (SIM). A several fold increase in systemic exposure of atorvastatin lactone has previously been observed in patients with SIM compared with healthy control subjects. In this study we aimed to investigate the association between polymorphisms in the UGT1A gene locus and plasma atorvastatin lactone levels.

    METHODS: DNA was extracted from whole blood obtained from a previous pharmacokinetic study of patients carefully diagnosed as having true SIM (n = 13) and healthy control subjects (n = 15). The UGT1A1*28(TA) 7 , UGT1A3*2, UGT1A3*3, and UGT1A3*6 polymorphisms were detected by pyrosequencing.

    RESULTS: Carriers of the low-expression allele UGT1A1*28(TA) 7 tended to have lower levels of atorvastatin lactone (p < 0.05) than carriers with the normal-activity allele (TA) 6.

    CONCLUSION: The low-expression UGT1A1*28(TA) 7 allele seems to be associated with decreased systemic exposure of the suspected muscle-toxic metabolite atorvastatin lactone.

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• Anatomic distribution of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium infections in men who have sex with men.

  Forfattere: Reinton N, Moi H, Olsen AO, Zarabyan N, Bjerner J, Tønseth TM, Moghaddam A.
  Publisert i: Sex Health. 2013 Jul;10(3):199-203.

  • Les utdrag

    BACKGROUND: New cases of gonorrhoea (Neisseria gonorrhoeae) and chlamydia (Chlamydia trachomatis) infections have been steadily increasing in Scandinavian countries over the last decade. There is a particular urgency in reducing new infections as isolation of multiple drug resistant strains of gonorrhoea is becoming more frequent. The aim of this study was to determine the prevalence and sites of infection of common sexually transmissible infections (STIs) in men who have sex with men (MSM).

    METHODS: We have performed a retrospective analysis of the three major STIs, gonorrhoea, chlamydia and Mycoplasma genitalium in urogenital, anorectal and oropharyngeal samples from MSM that attended two STI clinics in Oslo.

    RESULTS: One hundred and thirty-six men (6.0%) out of 2289 MSM tested were found to be positive for gonorrhoea using a porA gene targeted nucleic acid amplification test (NAAT). Of these, 106 (77.9%) would not have been identified through testing first-void urine alone. Two hundred and twenty eight (10.0%) patients from 2289 tested were found to be positive for chlamydia, 164 (71.9%) of which were identified through anorectal specimens. Ninety-one (5.1%) patients from 1778 tested were found to be positive for M. genitalium, with 65 (71.4%) identified through testing of anorectal specimens.

    CONCLUSIONS: Our results supports the European findings that the MSM population carries a high burden of STIs and that testing the anorectum and oropharynx will identify a significantly higher percentage of infected patients and reservoirs of STIs.

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• Respiratory tract infections during the 2011 Mycoplasma pneumoniae epidemic.

  Forfattere: Reinton N, Manley L, Tjade T, Moghaddam A.
  Publisert i: Eur J Clin Microbiol Infect Dis. 2013 Jun;32(6):835-40.

  • Les utdrag
    In 2011, Norway experienced a surge in community acquired Mycoplasma pneumoniae infections. Norway also has one of the highest rates of reported Bordetella pertussis infections, despite high vaccine coverage. We aimed to determine the prevalence of upper respiratory tract pathogens in patients attending primary care physicians for respiratory illness during the 2011 M. pneumoniae epidemic period. A retrospective analysis of data from 26,039 patients that have had nasopharyngeal swabs analysed by nucleic acid amplification testing (NAAT) for M. pneumoniae, C. pneumoniae and B. pertussis was performed. Subsets of samples were tested for additional pathogenic bacteria, including B. parapertussis and B. holmesii, as well as influenza virus. M. pneumoniae, C. pneumoniae and B. pertussis were detected in 2,484 (9.5 %), 261 (1.0 %) and 821 (3.2 %) patients, respectively. Co-infection of M. pneumoniae and B. pertussis was found in 50 (0.19 %) patients, C. pneumoniae and B. pertussis in 4 (0.02 %). Influenza virus was found in 899 (24.5 %) of 3,661 nasopharyngeal swabs. Co-infection of influenza virus and bacterial pathogens was common, although influenza virus co-infection with B. pertussis occurred significantly more often than with C. pneumoniae and M. pneumoniae (20.4 % versus 2.9 % and 9.1 %, respectively; p<0.005). Testing for Bordetella species genes IS1001, IS1002 and recA showed that B. holmesii was most likely misdiagnosed as B. pertussis in 5.8 % of cases. The most prevalent respiratory tract pathogen in the general population in 2011 was M. pneumoniae. B. pertussis was also found frequently as was B. pertussis and influenza virus co-infections.
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• Discrepancy between HbA1c and fasting glucose results

  Forfattere: Piehler AP, Grimholt RM, Bjerner J, Urdal P, Buchmann M
  Publisert i: Scand J Clin Lab Invest. 2013 Mar;73(2):186-8.

  • Les utdrag

    Case report

    SIR : A 51-year-old man from Northern Pakistan(parents from the Kashmir and Peshawar areas,respectively) with type 2 diabetes attended to hisgeneral practitioner for a routine visit. Previous laboratorytests had shown satisfactory HbA1c levels(5.0 – 5.9%, recommended  7%) analyzed with cation-exchange HPLC on a Tosoh G7 in standard mode.In contrast, simultaneously measured fasting glucoseconcentrations exhibited increased levels between 7.9and 11.4 mmol/L (142 and 205 mg/dL) [referenceinterval, 4.0 – 6.0 mmol/L (72 – 108 mg/dL)].

    [...]

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• Recommended Nordic paediatric reference intervals for 21 common biochemical properties.

  Forfattere: Hilsted L, Rustad P, Aksglæde L, Sørensen K, Juul A.
  Publisert i: Scand J Clin Lab Invest. 2013 Feb;73(1):1-9.

  • Les utdrag
    Paediatric reference intervals based on samples from healthy children are difficult to establish and consequently data are often from hospitalized children. Furthermore, biases may present in published data due to differences in the analytical methods employed. Blood samples from 1429 healthy Danish children were collected for establishing reference intervals for 21 common biochemical properties (Alanine transaminase, Albumin, Alkaline phosphatase, Aspartate transaminase, Bilirubin, Calcium, Cholesterol, Creatinine, Creatine kinase, HDL-Cholesterol, Iron, Lactate dehydrogenase, LDL- Cholesterol, Magnesium, Phosphate, Potassium, Protein, Sodium, Transferrin, Triglycerides and Urate). Samples were analyzed on a Roche-Modular-P/ISE-system. The NORIP reference material (NFKK Reference Serum X) was included in all the analytical runs. Reference values were recalculated according to the target values of X for the properties and statistical calculations carried out as performed in the NORIP study. Thus commutable (regarding analytical method) reference intervals for 20 properties were established and for LDL-Cholesterol reference intervals were reported for the specific analytical method employed. The data were compared to previous studies and to those obtained from the youngest age group in the NORIP study. Marked age differences were observed for most of the properties. Several properties also showed gender-related differences, mainly at the onset of puberty. Data are presented as suggested intervals for combined age groups, but can be accessed via the NORIP home page if more detailed division according to age or gender is desired.
    
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• Infeksjon; medisinsk mikrobiologi, infeksjonssykdommer, smittevern. Repetisjon og oppgaver.

  Forfattere: Trygve Tjade
  Publisert i: Gyldendal Akademisk. 1. utgave 2012. ISBN 978-82-05-42449-4.

  • Les utdrag
    Dette heftet tar for seg sentrale temaer i medisinsk mikrobiologi, infeksjonssykdommer og smittevern for bachelorstudenter i helsefag.
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• Metabolic changes in urine during and after pregnancy in a large, multiethnic population-based cohort study of gestational diabetes.

  Forfattere: Sachse D, Sletner L, Mørkrid K, Jenum AK, Birkeland KI, Rise F, Piehler AP, Berg JP
  Publisert i: PLoS One. 2012;7(12):e52399.

  • Les utdrag
    This study aims to identify novel markers for gestational diabetes (GDM) in the biochemical profile of maternal urine using NMR metabolomics. It also catalogs the general effects of pregnancy and delivery on the urine profile. Urine samples were collected at three time points (visit V1: gestational week 8–20; V2: week 28±2; V3:10–16 weeks post partum) from participants in the STORK Groruddalen program, a prospective, multiethnic cohort study of 823 healthy, pregnant women in Oslo, Norway, and analyzed using 1H-NMR spectroscopy. Metabolites were identified and quantified where possible. PCA, PLS-DA and univariate statistics were applied and found substantial differences between the time points, dominated by a steady increase of urinary lactose concentrations, and an increase during pregnancy and subsequent dramatic reduction of several unidentified NMR signals between 0.5 and 1.1 ppm. Multivariate methods could not reliably identify GDM cases based on the WHO or graded criteria based on IADPSG definitions, indicating that the pattern of urinary metabolites above micromolar concentrations is not influenced strongly and consistently enough by the disease. However, univariate analysis suggests elevated mean citrate concentrations with increasing hyperglycemia. Multivariate classification with respect to ethnic background produced weak but statistically significant models. These results suggest that although NMR-based metabolomics can monitor changes in the urinary excretion profile of pregnant women, it may not be a prudent choice for the study of GDM.
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• Recovery of Bordetella pertussis from PCR-positive Nasopharyngeal Samples is Dependent on Bacterial Load.

  Forfattere: Vestrheim DF, Steinbakk M, Bjørnstad ML, Moghaddam A, Reinton N, Dahl ML, Grude N, Sandven P.
  Publisert i: J Clin Microbiol. 2012 Dec;50(12):4114-5.

  • Les utdrag
    Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load.
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• A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus

  Forfattere: Stormo C, Kringen MK, Grimholt RM, Berg JP, Piehler AP
  Publisert i: BMC Mol Biol. 2012 Sep 18;13(1):29.

  • Les utdrag

    BACKGROUND: The major rate-limiting enzyme for de novo cholesterol synthesis is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). HMGCR is sterically inhibited by statins, the most commonly prescribed drugs for the prevention of cardiovascular events. Alternative splicing of HMGCR has been implicated in the control of cholesterol homeostasis. The aim of this study was to identify novel alternatively spliced variants of HMGCR with potential physiological importance.

    RESULTS: Bioinformatic analyses predicted three novel HMGCR transcripts containing an alternative exon 1 (HMGCR-1b, -1c, -1d) compared with the canonical transcript (HMGCR-1a). The open reading frame of the HMGCR-1b transcript potentially encodes 20 additional amino acids at the N-terminus, compared with HMGCR-1a. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to examine the mRNA levels of HMGCR in different tissues; HMGCR-1a was the most highly expressed variant in most tissues, with the exception of the skin, esophagus, and uterine cervix, in which HMGCR-1b was the most highly expressed transcript. Atorvastatin treatment of HepG2 cells resulted in increased HMGCR-1b mRNA levels, but unaltered proximal promoter activity compared to untreated cells. In contrast, HMGCR-1c showed a more restricted transcription pattern, but was also induced by atorvastatin treatment.

    CONCLUSIONS: The gene encoding HMGCR uses alternative, mutually exclusive exon 1 sequences. This contributes to an increased complexity of HMGCR transcripts. Further studies are needed to investigate whether HMGCR splice variants identified in this study are physiologically functional.

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• Calcium, Magnesium, Albumin, and Total-Protein Measurement in Serum as Assessed with 20 Fresh-Frozen Single-Donation Sera.

  Forfattere: Van Houcke SK, Rustad P, Stepman HC, Kristensen GB, Stöckl D, Røraas TH, Sandberg S, Thienpont LM.
  Publisert i: Clin Chem. 2012 Nov;58(11):1597-9.

  • Les utdrag
    To the Editor:
    The scope of external quality assessment (EQA) in laboratory medicine has evolved considerably (1). With the increasing worldwide interest in the use of common reference intervals and/or medical-decision limits, modern EQA schemes need to be better at assessing the standardization status of commercial in vitro diagnostic tests. This need has led to new challenges in the design of EQA surveys.
    We report the outcomes of a Norwegian pilot study that investigated the use of commutable, fresh-frozen single donations to assess the current standardization status as part of an initiative toward producing common reference intervals (2). 
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• Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.

  Forfattere: Eskesen AN, Melum E, Moghaddam A, Bjøro K, Verbaan H, Ring-Larsen H, Dalgard O.
  Publisert i: Eur J Gastroenterol Hepatol. 2012 Aug;24(8):890-896.

  • Les utdrag

    OBJECTIVES: Two functional genetic variants in the inosine triphosphatase (ITPA) gene have been shown to be strongly associated with protection from ribavirin (RBV)-induced hemolysis. We aimed at evaluating this finding in a chronic hepatitis C genotype 2/3 cohort with a predominance of genotype 3 patients where available data are scarce. A second objective was to determine whether a protective association translated into the need for RBV reduction and hence a possible impact on treatment response.

    METHODS: Overall, 457 patients were recruited from two trials of genotype 2/3 patients treated with pegylated interferon α-2b and weight-based RBV. rs1127354 and rs7270101 were genotyped and a composite ITPAase deficiency variable was graded according to the two single nucleotide polymorphisms. The primary endpoints were hemoglobin (Hb) decline from baseline and Hb decline of more than 3 g/dl at week 4.RESULTS: Both single nucleotide polymorphisms and the composite ITPAase deficiency variable were strongly and independently associated with protection from a decline in Hb at week 4 in multivariate linear regression models (Prs1127354=7.0×10, Prs7270101=0.0036, PITPase deficiency variable =6.3×10). Patients with any degree of reduced ITPAase activity were less likely to have their RBV dose reduced (odds ratio 0.39, 95% confidence interval 0.16-0.96, P=0.040), although this did not translate into increased rapid viral response or sustained viral response (Prvr=0.93, Psvr=0.22).

    CONCLUSION: We have confirmed a strong association between functional ITPA variants and RBV-induced hemolysis and showed protection from RBV dose reduction, although this did not translate into increased rapid viral response or sustained viral response.

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• Copy number variations of the ATP-binding cassette transporter ABCC6 gene and its pseudogenes

  Forfattere: Kringen MK, Stormo C, Grimholt RM, Berg JP, Piehler AP.
  Publisert i: BMC Research Notes 2012, 5:425

  • Les utdrag

    Background:

    The ATP-binding cassette transporter ABCC6 gene is located on chromosome 16 between its two pseudogenes (ABCC6P1 and ABCC6P2). Previously, we have shown that ABCC6P1 is transcribed and affects ABCC6 at the transcriptional level. In this study we aimed to determine copy number variations of ABCC6, ABCC6P1 and ABCC6P2 in different populations. Moreover, we sought to study the transcription pattern of ABCC6 and ABCC6 pseudogenes in 39 different human tissues.

    Findings:

    Genomic DNA from healthy individuals from five populations, Chinese (n = 24), Middle East (n = 20), Mexicans (n = 24), Caucasians (n = 50) and Africans (n = 24), were examined for copy number variations of ABCC6 and its pseudogenes by pyrosequencing and quantitative PCR. Copy number variation of ABCC6 was very rare (2/142; 1.4%). However, one or three copies of ABCC6P1 were relatively common (3% and 8%, respectively). Only one person had a single copy of ABCC6P2 while none had three copies. In Chinese, deletions or duplications of ABCC6P1 were more frequent than in any other population (9/24; 37.5%). The transcription pattern of ABCC6P2 was highly similar to ABCC6 and ABCC6P1, with highest transcription in liver and kidney. Interestingly, the total transcription level of pseudogenes, ABCC6P1 + ABCC6P2, was higher than ABCC6 in most tissues, including liver and kidney.

    Conclusions:

    Copy number variations of the ABCC6 pseudogenes are quite common, especially in populations of Chinese ancestry. The expression pattern of ABCC6P2 in 39 human tissues was highly similar to that of ABCC6 and ABCC6P1 suggesting similar regulatory mechanisms for ABCC6 and its pseudogenes.

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• Belief is only half the truth – or why screening for heterophilic antibody interference in certain assays makes double sense

  Forfattere: Bjerner J, Bolstad N, Piehler AP.
  Publisert i: Ann Clin Biochem. 2012 Jul;49(Pt 4):381-6.

  • Les utdrag

    Introduction:

    Interference in immunoassays may cause both false negative and false positive results.It may be detected using a number of affirmative tests such as re-analysis of certain samples usingdifferent asssay’s platform with known bias; after the addition of blockers antibodies or assessmentof linearity and parallelism following serial doubling dilutions.One should look for interference where it is likely and has high medical impact. Probabilistic Bayesianreasoning is a statistical tool to identify samples where interference is most likely. But when lookingfor interference where it is likely, do we find it where it has the largest population healthconsequences?

    Methods:

    We use information theory to quantify the effect of assay interference by calculating theShannon information content (using logarithms with base 2). We then obtain lower bounds of thepopulation health consequences of a particular test and combine these expressions to get lowerbounds of the population health consequences of interference

    Results and conclusion:

    We suggest that assays having a low frequency of true positives should bethe primary target of retesting, because: (i) assays with a low frequency of true positives exhibit ahigh likelihood of interference and (ii) the population health consequences of false positive resultsare generally higher for assays with a low frequency of true positives. Finally, we give a workedexample having a realistic frequency of interference and test costs. In some immunoassays (e.g.)tumour marker), adding a blocker to all tests can be a more cost-efficient mean than retestingpositive samples.

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• Reticulocyte hemoglobin equivalent to detect thalassemia and thalassemic hemoglobin variants

  Forfattere: Sudmann AA, Piehler AP, Urdal P.
  Publisert i: Int J Lab Hematol. 2012 Jul 6.

  • Les utdrag

    INTRODUCTION:

    Thalassemia and iron deficiency may both result in hypochromic microcytic anemia. Hematological algorithms that differentiate the two are mainly established in adult selected diagnostic groups. We aimed at creating an algorithm applicable in the presence of children, hemoglobin variants, and iron deficiency.

    METHODS:

    Our study material constituted blood samples referred during 1 year for routine diagnostics of hemoglobinopathy. We included 443 samples, of which 37% were from children 3 months or older. We found β-thalassemia trait, α-thalassemia, combined α-/β-thalassemia hemoglobin variants, and no-hemoglobinopathy, of whom 107 had a ferritin at or below 20 μg/L. We included reticulocyte hemoglobin equivalent, ferritin, and erythrocyte count in our algorithm.

    RESULTS:

    Our algorithm differentiated β-thalassemia from no-hemoglobinopathy with a sensitivity of 99% at 83% specificity. It performed better than other published algorithms when applied to all patient samples, while equally or moderately better in the 63% adult samples. Our algorithm also detected the clinically significant α-thalassemias, and most of the combined α-/β-thalassemias and thalassemic hemoglobin variants.

    CONCLUSION:

    Our algorithm efficiently differentiated thalassemia and thalassemic hemoglobin variants from iron deficiency in children and adults.

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• Commentary on "Pleural effusion in a patient with multiple myeloma."

  Forfattere: Piehler ap
  Publisert i: Clin Chem. 2012 Apr;58(4):675-6.

  • Les utdrag
    Whereas pleural effusions in multiple myeloma (MM) due to benign causes, including heart failure, renal impairment, and hypoalbuminemia, occur in about 6% of all patients, myelomatous pleural effusion (MPE) is a rarity. MPE indicates an aggressive course of MM, with an associated median survival time of approximately 4 months. Thus, prompt and appropriate workup of pleural effusions in MM is imperative. In addition to detection of atypical plasma cells in the pleural fluid and histologic confirmation of MPE, identification of a monoclonal protein in the pleural effusion is essential. Protein electrophoresis is often used. As in the case described by Oudart et al., however, light chain MM may represent a diagnostic obstacle, because only about 50% of cases exhibit a monoclonal band after serum protein electrophoresis, and even immunofixation of serum may not demonstrate a monoclonal band in all patients with light chain MM. In the reported case, immunofixation analysis and quantification of free light chains in the pleural effusion demonstrated the presence of monoclonal free light chains. Quantification of free light chains in a pleural effusion is a novel approach, and a higher concentration of free light chains in the pleural effusion than in the serum indicated local production in this case. With a median survival time of about 4 months in MPE patients, neither patients nor physicians have much time to obtain a proper diagnosis and to start adequate therapy. In such cases, the most sensitive diagnostic methods have to be used. Today, the most sensitive routine tests for detecting monoclonal components in serum are a combination of protein electrophoresis, immunofixation, and free light chain quantification. This is most likely also true for the detection of monoclonal proteins in pleural effusions, and these methods should therefore also be used to uncover the origin of pleural effusions associated with MM.
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• Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum among students in northern Norway.

  Forfattere: Jensen AJ, Kleveland CR, Moghaddam A, Haaheim H, Hjelmevoll SO, Skogen V.
  Publisert i: J Eur Acad Dermatol Venereol. 2012 Mar 26

  • Les utdrag

    BACKGROUND: The prevalence of Mycoplasma genitalium and Ureaplasma genitalium in populations outside sexually transmitted infection clinics in Norway is unknown.

    OBJECTIVE: To assess the prevalence of potential sexually transmitted organisms in a non-clinical setting, among college students in Northern Norway.

    METHODS: In total 655 students, 449 men and 206 women, were tested for Chlamydia trachomatis, M. genitalium, and U. urealyticum by nucleic acid amplification testing of urine samples. All subjects completed questionnaires.

    RESULTS: Among the included men, the prevalences of C. trachomatis, M. genitalium, and U. urealyticum were 4.2%, 1.1% and 8.9%, respectively. Prevalence among included women was 1.9%, 1% and 8.2%, respectively. In men, the number of sexual partners in the preceding 6 months was associated with prevalence of U. urealyticum and C. trachomatis.

    CONCLUSIONS: U. urealyticum appeared more prevalent than C. trachomatis and increased number of sexual partners was associated with increased risk of a positive test. M. genitalium had a low prevalence.

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• A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and Neurodegeneration.

  Forfattere: Piehler AP, Ozcürümez M, Kaminski WE.
  Publisert i: Front Psychiatry. 2012;3:17.

  • Les utdrag
    The A-subclass of ATP-binding cassette (ABC) transporters comprises 12 structurally related members of the evolutionarily highly conserved superfamily of ABC transporters. ABCA transporters represent a subgroup of “full-size” multispan transporters of which several members have been shown to mediate the transport of a variety of physiologic lipid compounds across membrane barriers. The importance of ABCA transporters in human disease is documented by the observations that so far four members of this protein family (ABCA1, ABCA3, ABCA4, ABCA12) have been causatively linked to monogenetic disorders including familial high-density lipoprotein deficiency, neonatal surfactant deficiency, degenerative retinopathies, and congenital keratinization disorders. Recent research also point to a significant contribution of several A-subfamily ABC transporters to neurodegenerative diseases, in particular Alzheimer’s disease (AD). This review will give a summary of our current knowledge of the A-subclass of ABC transporters with a special focus on brain lipid homeostasis and their involvement in AD.
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• Human epididymis protein 4 reference limits and natural variation in a Nordic reference population.

  Forfattere: Bolstad N, Oijordsbakken M, Nustad K, Bjerner J.
  Publisert i: Tumour Biol. 2012 Feb;33(1):141-8.

  • Les utdrag
    The objectives of this study are to establish reference limits for human epididymis protein 4, HE4, and investigate factors influencing HE4 levels in healthy subjects. HE4 was measured in 1,591 samples from the Nordic Reference Interval Project Bio-bank and Database biobank, using the manual HE4 EIA (Fujirebio) for 802 samples and the Architect HE4 (Abbott) for 792 samples. Reference limits were calculated using the statistical software R. The influence of donor characteristics such as age, sex, body mass index, smoking habits, and creatinine on HE4 levels was investigated using a multivariate model. The study showed that age is the main determinant of HE4 in healthy subjects, corresponding to 2% higher HE4 levels at 30 years (compared to 20 years), 9% at 40 years, 20% at 50 years, 37% at 60 years, 63% at 70 years, and 101% at 80 years. HE4 levels are 29% higher in smokers than in nonsmokers. In conclusion, HE4 levels in healthy subjects are associated with age and smoking status. Age-dependent reference limits are suggested.
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• Evolutionary history and functional characterization of three large genes involved in sporulation in Bacillus cereus group bacteria.

  Forfattere: Reiter L, Tourasse NJ, Fouet A, Loll R, Davison S, Økstad OA, Piehler AP, Kolstø AB.
  Publisert i: J Bacteriol. 2011 Oct;193(19):5420-30.

  • Les utdrag
    The Bacillus cereus group of bacteria is a group of closely related species that are of medical and economic relevance, including B. anthracis, B. cereus, and B. thuringiensis. Bacteria from the Bacillus cereus group encode three large, highly conserved genes of unknown function (named crdA, crdB, and crdC) that are composed of 16 to 35 copies of a repeated domain of 132 amino acids at the protein level. Bioinformatic analysis revealed that there is a phylogenetic bias in the genomic distribution of these genes and that strains harboring all three large genes mainly belong to cluster III of the B. cereus group phylogenetic tree. The evolutionary history of the three large genes implicates gain, loss, duplication, internal deletion, and lateral transfer. Furthermore, we show that the transcription of previously identified antisense open reading frames in crdB is simultaneously regulated with its host gene throughout the life cycle in vitro, with the highest expression being at the onset of sporulation. In B. anthracis, different combinations of double- and triple-knockout mutants of the three large genes displayed slower and less efficient sporulation processes than the parental strain. Altogether, the functional studies suggest an involvement of these three large genes in the sporulation process.
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• Heterophilic antibody interference in commercial immunoassays; a screening study using paired native and pre-blocked sera.

  Forfattere: Bolstad N, Warren DJ, Bjerner J, Kravdal G, Schwettmann L, Olsen KH, Rustad P, Nustad K.
  Publisert i: Clin Chem Lab Med. 2011 Sep 8.

  • Les utdrag
    Abstract Background: Heterophilic antibodies are still an important source of interference in immunoassays. We have conducted a screening study for interference in a panel of commercially available assays using two sera known to contain high titer Fc-reactive heterophilic antibodies. Methods: The sera were distributed to laboratories participating in the Nordic External Quality Assessment cooperation (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33 were also supplied. Discrepancies (>50%) between the results for native and blocked samples were used to classify the tested assays as susceptible to interference. A total of 170 different assay kits covering 91 analytes were tested. Results: We found that 21 assays, covering 19 different analytes, were susceptible to interference from the heterophilic antibodies in the two sera. Many of these are clinically and commercially important assays. Some of the false results were grossly elevated and could have been detrimental to patient care in a clinical setting. Conclusions: Heterophilic antibodies with Fc-reactivity remain a threat. A more widespread use of antibody fragments and aggregated immunoglobulin could potentially improve the heterophilic antibody resistance of assays intended for clinical use.
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• Effect of ambient temperature on analytical performance of self-monitoring blood glucose systems.

  Forfattere: Nerhus K, Rustad P, Sandberg S.
  Publisert i: Diabetes Technol Ther. 2011 Sep;13(9):883-92.

  • Les utdrag

    BACKGROUND: The analytical quality of self-monitoring of blood glucose (SMBG) can be affected by environmental conditions such as temperature. The objective of this study was to determine the influence of (1) a shift in the ambient temperature immediately before measurement and (2) taking measurements in the lower and upper part of the operating temperature range.

    METHODS: Nine different SMBG systems on the Norwegian market were tested with heparinized venous blood (4.8 and 19.0 mmol/L). To test the shift in ambient temperature effect, the glucometer and strips were equilibrated for 1 h at 5°C or 1 h at 30°C before the meter and strips were moved to room temperature, and measurements were performed after 0, 5, 10, 15, and 30 min. To test the lower and upper temperature range, measurements were performed at 10°C and at 39°C after 1 h for temperature equilibration of the glucometer and strips. All these measurements were compared with measurements performed simultaneously on a meter and strips kept at room temperature the whole time.

    RESULTS: Six of nine SMBG systems overestimated and/or underestimated the results by more than 5% after moving meters and strips from 5°C or 30°C to room temperature immediately before the measurements. Two systems underestimated the results at 10°C. One system overestimated and another underestimated the results by more than 5% at 39°C.

    CONCLUSIONS: The effect on analytical performance was most pronounced after a rapid shift in the ambient temperature. Therefore patients need to wait at least 15 min for temperature equilibration of affected meters and strips before measuring blood glucose.

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• Reference genes for quantitative, reverse-transcription PCR in Bacillus cereus group strains throughout the bacterial life cycle.

  Forfattere: Reiter L, Kolstø AB, Piehler AP.
  Publisert i: J Microbiol Methods. 2011 Aug;86(2):210-7.

  • Les utdrag
    Quantitative reverse-transcription PCR (RT-qPCR) has become a major tool to better understand the biology and pathogenesis of bacteria. One prerequisite of valid RT-qPCR data is their proper normalization to stably expressed reference genes. To identify and evaluate reference genes suitable for normalization of gene expression data in Bacillus cereus group strains, mRNA levels of eleven candidate reference genes (rpsU, nifU, udp (UDP-N-acetylglucosamine 2-epimerase), BT9727_5154/BC_5475, BT9727_4034/BC_4293, BT9727_4549/BC_4813, pspA, gatB_Yqey (gatB_Yqey domain containing protein), helicase (SWF/SNF family protein), adk and pta) and a target gene (BT9727_3305/BC3547+BC3546) were quantified by RT-qPCR at different time points throughout the entire life cycle of the wild-type B. cereus ATCC 14579 and Bacillus thuringiensis subsp. konkukian 97-27, a phylogenetically closely related strain to Bacillus anthracis. The programs geNorm and Normfinder were used to calculate expression stabilities and identified the genes gatB_Yqey, rpsU and udp as the most stably expressed reference genes. Compared to this combination or the sets of reference genes as recommended by geNorm or Normfinder, normalization using a traditional housekeeping gene (adk) alone resulted in significantly different gene expression results and in a significant overestimation of the target gene transcription. Normalization of the data to the reference gene gatB_Yqey alone showed no or only small differences to the reference gene combinations indicating that gatB_Yqey may be used as a single reference gene when investigating rather large changes in mRNA transcription. Otherwise, a combination of the stably expressed reference genes is recommended. In conclusion, the present study underlines the importance of normalization to stably expressed reference genes and presents valid endogenous controls suitable for normalization of transcriptional data throughout the life cycle of B. cereus group strains.
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• En inte så kort introduktion till probabilistiska (Bayesianska) metoder

  Forfattere: Bjerner J.
  Publisert i: Klinisk Biokemi i Norden. 2011;3:38-42.

  • Les utdrag
    Precis som datavärlden har sina Windows och Macintoshanhängare, så är statistik ofta delat mellan anhängare av ”klassiska metoder” och ”probabilistiska metoder”. En grov gissning är väl att statistikvärlden fördelar sig 50/50 mellan dessa, och diskussionen mellan anhängarna är ofta både intensiv och emotionell. I medicinsk biokemi har alltid ”klassiska metoder” dominerat fullständigt, men en ändring verkar vara på väg. Den mycket omdiskuterade ekvationen för att beräkna ”estimated average glucose” från HbA1c blev härledd med probabilistiska metoder
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• Standardisert hemoglobin A1c til diagnostisk bruk?

  Forfattere: Berg JP, Hanssen KF, Bjerve KS, Claudi T, Dahl-Jørgensen K, Rustad P, Sandberg S, Skrivarhaug T.
  Publisert i: Tidsskr Nor Laegeforen. 2011 Mar 18;131(6):565-6.

  • Les utdrag
    Analyse av hemoglobin A1c (HbA1c) er det viktigste hjelpemidlet til å vurdere hvor godt regulert blodsukkernivået til en pasient med diabetes er over tid. I januar i år anbefalte WHOs ekspertgruppe at måling av HbA1c også kan benyttes diagnostisk. Dette vil gjøre det enklere å diagnostisere diabetes, men forutsetter en standardisert analyse av høy kvalitet.
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• IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection

  Forfattere: Moghaddam A., Melum E., Reinton N., Ring-Larsen H., Verbaan H., Bjøro K. og Dalgard O.
  Publisert i: Hepatology. 2011 Mar;53(3):746-54.

  • Les utdrag
    Polymorphisms near the IL28B gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 × 10(-5) ; rs8099917, P = 3 × 10(-4) ). In multivariate analysis, age (<40 years), baseline viral load (<4 × 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 × 10(-5) ; rs8099917, P = 7.3 × 10(-6) ). CONCLUSION: Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients.
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• Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.

  Forfattere: Lødrup Carlsen KC, Söderström L, Mowinckel P, Håland G, Pettersen M, Munthe Kaas MC, Devulapalli CS, Buchmann M, Ahlstedt S, Carlsen KH.
  Publisert i: Allergy. 2010 Sep;65(9):1134-40.

  • Les utdrag

    BACKGROUND: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA.

    METHODS: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification.

    RESULTS: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only.

    CONCLUSION: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only.

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• Lineær regresjon med flere variabler.

  Forfattere: Bjerner J.
  Publisert i: Klinisk Biokemi i Norden. 2010;4:36-41.

  • Les utdrag

    ”Når jeg går til min lege vil jeg at han skal gi meg den beste medisinen, ikke den beste medisinen som han forstår virkningen av.” Engelsk statistiker om leger og statistiske modeller .

    I medisinsk biokjemi har vi ofte flere enn to variabler. Vi vet at gamma-GT er økt både for personer med høyt alkoholinntak og for personer med høy BMI. Hva med en person som har høy BMI, vil alkoholinntak føre til enda høyere gamma-GT eller ikke? Med lineær regresjon kan vi se sammenhenger mellom flere variabler

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• Den svenske Chlamydiavarianten nvC. trachomatis i Norge

  Forfattere: Reinton N., Moi H., Bjerner J., Moghaddam A.
  Publisert i: Tidsskr Nor Legeforen nr. 4, 2010; 130: 380–1.

  • Les utdrag

    Bakgrunn. En variant av Chlamydia trachomatis (nvC trachomatis) har skapt problemer for chlamydiadiagnostikken i Sverige. Andelen nvC trachomatis i Sverige i 2006–07 var fylkesvis 25–80 % av dem som var smittet av C trachomatis. Vårt formål har vært å overvåke nvC trachomatis blant våre pasienter fra januar 2007 frem til juli 2008.

    Materiale og metode. 1.1. 2007–30.6. 2008 ble alle chlamydiaprøver ved Fürst Medisinsk Laboratorium dobbeltanalysert. Deteksjon av C trachomatis ble utført på isolert DNA med Cobas TaqMan 48 (Roche Diagnostics). Deteksjon og verifikasjon av nvC trachomatis ble utført med egenutviklede sanntid polymerasekjedereaksjonsmetoder.

    Resultater. 61 av 23 726 pasienter ble identifisert som bærere av nvC trachomatis. Andelen C trachomatis-bærere som var nvC trachomatis-positive økte fra 1,0 % i første kvartal 2007 til 3,2 % i andre kvartal 2008.

    Fortolkning. Våre resultater viser en langsom, men jevn økning i andelen nvC trachomatis-positive prøver. Sammenliknet med tidligere prevalenstall rapportert i Sverige (25–80 %), er forekomsten av nvC trachomatis lav i våre data. Epidemiologien til nvC trachomatis bidrar til kunnskapen om spredning av seksuelt overførbare infeksjoner og understreker at man finner bare det man leter etter.

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• Characterization of Treatment Response to Recombinant Interferon-a2b in Osteosarcoma Xenografts

  Forfattere: Müller CR, Namløs HM, Bjerner J, Østensen IHG, Saeter G, Smeland S, Bruland ØS, Myklebost O.
  Publisert i: J Cancer Sci Ther. 2010;2:33-42.

  • Les utdrag
    Interferons (IFNs) may target cancer cells both through their regulation of the immune response, effect on angiogenesis and through direct effect on cancer cells. Treatment response has been demonstrated in osteosarcoma patients, but tumour resistance to IFN-a is common. Hence, understanding the molecular mechanisms involved in response and resistance is essential for improving therapeutic efficacy. Of five xenografts screened for specific growth delay in response to treatment with unconjugated and PEGylated IFN-a2b, one displayed growth inhibition and tumour shrinkage. Growth inhibition increased on a dosing schedule of PEGylated IFN every third day. Xenografts resistant to PEGylated IFN were similarly resistant to unconjugated IFN. Combination treatment with IFN-a2b and doxorubicin resulted in improved growth control rates. Transcriptional profiling analysis of the one sensitive and two resistant xenografts identified a common set of 79 genes significantly affected by IFN- a2b treatment independent of tumour growth inhibition. All but four of the 79 genes were up-regulated. The majority of these genes were well characterized IFN-stimulated genes and core members of the IFN-a signalling pathway. The expression of a set of 128 unique genes changed only in the sensitive xenograft; 52/128 genes were up-regulated. The specific geneexpression pattern seen in the responsive xenograft identified possible pathways important for the antitumor effect of IFN-a in osteosarcoma, including subsets of genes involved in cell adhesion and osteogenic tissue development. The observed improved control rates of combined treatment with IFN and doxorubicin are encouraging and should be further explored.
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• Bestemmelse av utlekking av metaller fra odontologiske legeringer i cellekulturmedium ved induktivt koplet plasma massespektrometri (ICP-MS)

  Forfattere: Kalfoss T.
  Publisert i: Masteroppgave ved Universitetet for miljø- og biovitenskap, Jun 2010

  • Les utdrag

    Det finnes over tusen odontologiske legeringer på markedet i dag, og bruken av uedle legeringer har i stor grad erstattet bruken av gullbaserte legeringer. Felles for disse legeringene er at de er i kontakt med oralt vev, og at metaller lekker fra legeringene ut i munnhulen. Det stilles derfor mange spørsmål om den biologiske sikkerheten omkring bruken av disse legeringene. Korrosjonstester, hvor de ulike legeringene blir utsatt for det samme sure miljøet som finnes i munnhulen, har vist at uedle legeringer lekker ut større konsentrasjoner av metaller sammenlignet med edle legeringer.

    Nordisk Institutt for Odontologiske Materialer (NIOM) har undersøkt ekstrakter av ulike legeringer i cellekulturer og sett på hvilken påvirkning de har på cellene. I den sammenheng ønsket de å kvantifisere utlekking av metaller fra de ulike legeringene i cellekulturmediet for å bestemme konsentrasjonen av de ulike grunnstoffene som cellene hadde blitt utsatt for.  Fürst Medisinsk Laboratorium fikk i oppdrag å utvikle en metode for kvantitativ bestemmelse av grunnstoffer i Minimal Essential Medium with Earle’s salts (MEM).

    Atten ulike odontologiske legeringer, hovedsakelig uedle, ble sandlåst, slipt og renset før inkubering i MEM cellekulturmedium under bevegelse i tre døgn ved 37 C. Legeringene ble deretter fjernet fra mediet og løsningene ble analysert ved induktivt koplet plasma massespektrometri (ICP-MS).  Alle prøvene ble analysert for grunnstoffene litium (Li), beryllium (Be), aluminium (Al), vanadium (V), mangan (Mn), kobolt (Co), nikkel (Ni), kobber (Cu), sink (Zn), gallium (Ga), arsen (As), selen (Se), rubidium (Rb), strontium (Sr), yttrium (Y), zirkonium (Zr), niob (Nb), molybden (Mo), ruthenium (Ru), palladium (Pd), sølv (Ag), kadmium (Cd), indium (In), tinn (Sn), antimon (Sb), cesium (Cs), barium (Ba), lantan (La), cerium (Ce), praseodym (Pr), neodym (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), hafnium (Hf), tantal (Ta), wolfram (W), rhenium (Re), osmium (Os), iridium (Ir), platina (Pt), gull (Au), bly (Pb), vismut (Bi) og thorium (Th). Resultater fra analysering av de odontologiske legeringene viste bare utlekking av de metallene som var oppgitt fra produsenten av legeringene, og det er kun disse grunnstoffene som er presentert i resultatkapittelet. Som korrosjonstestene gav også her de uedle legeringene et høyere utslipp av metaller enn de edle legeringene. 

    Målemetoden som ble utviklet på ICP-MS gav tifredsstillende deteksjons- og kvantifiseringsgrenser, gjenfinning, presisjon og nøyaktighet for grunnstoffene Cr, Mn, Co, Ni, Cu, Zn, Ga, Nb, Mo, In, Sn, W, Pt og Au. Metoden gav bare ca 80 % gjenfinning av Ag og den kunne ikke brukes for bestemmelse av Pd < 50 µg/L. Metoden hadde ikke tilstrekkelig sensitivitet for bestemmelse av Fe på det nivået som lakk fra de 18 legeringene som ble analysert i denne oppgaven. Den største usikkerheten i metoden lå i prepareringen av løsningene. For mye manipulering av noen av legeringene ødela det beskyttende oksidlaget som ble dannet på overflaten og økte dermed utlekking av metaller.

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• NORIP og NOBIDA fyller ti år!

  Forfattere: Bjerner J.
  Publisert i: Klinisk Biokemi i Norden. 2010;1:36.

  • Les utdrag

    Nordisk referanseintervallprosjekt (NORIP) ble iverksatt i 1999-2000. initiativtakere var opprinnelig  heidi Steensland og Petter Urdal som ved hjelp av NFKK fikk etablert en samnordisk gruppe som koordinerte studiet: Peter Felding,  Leifur Franzson, Veli Kairisto, Per Hyltoft Pedersen, Pål Rustad og Per Simonsson.

    Friske individer mellom 18 og 80 år ble rekruttert på i alt 80 laboratorier i de nordiske landene og det ble samlet inn serum, plasma og fullblod . Prøvetakingen var nøye standardisert . Prøvene ble analysert for de vanligste komponentene i medisinsk biokjemi lokalt på de deltakende laboratoriene sammen med kontroller fra prosjektet, spesielt det som etter hvert ble kalt NFKK Reference Serum X. I tillegg ble materiale frosset ved – 80° C

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