Niels Graudal

Publications (20)128.13 Total impact

• Article: The (political) science of salt revisited.

  Niels Graudal, Gesche Jürgens
  BMJ (Clinical research ed.). 01/2013; 346:f2741.
• Article: The level of the indication of biologic agents in the 2012 ACR recommendations on the treatment of Rheumatoid Arthritis.

  Niels Graudal, Gesche Jürgens
  Arthritis care & research. 10/2012;
• Article: Effect of golimumab combined with methotrexate on radiographic progression in rheumatoid arthritis: comment on the article by Emery et al.

  Niels Graudal, Gesche Jürgens
  Arthritis & Rheumatism 01/2012; 64(4):1297-8; author reply 1298-9. · 7.87 Impact Factor
• Article: Reanalysis of NHANES III data on sodium association with mortality: appropriate adjustment for potassium not performed.

  Hillel W Cohen, Michael Aldermann, Niels Graudal
  Archives of internal medicine 12/2011; 171(22):2063; author reply 2064. · 11.46 Impact Factor
• Article: Effect of the TNF-α inhibitor adalimumab in patients with recalcitrant sarcoidosis: a prospective observational study using FDG-PET.

  Nils Milman, Niels Graudal, Annika Loft, Jann Mortensen, Janni Larsen, Bo Baslund
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  ABSTRACT: Background:  Tumour necrosis factor-alpha (TNF-α) plays a crucial role in sarcoidosis. In severe disease, treatment with TNF-α inhibitors may be effective. Objectives:  Changes in sarcoid disease activity were assessed by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with recalcitrant sarcoidosis treated with adalimumab. Methods:  Prospective 24-week observational study. Patients continued medication with steroids and antimetabolites and received adalimumab 40 mg subcutaneously every other week. Ten patients with biopsy-proven sarcoidosis (two men) were included with a median age of 47 years (range 35-73). An FDG-PET showing uptake indicating sarcoid activity was required at inclusion and repeated at the end of the study. FDG-PET uptake was assessed by calculated standardised uptake value (SUV). Blood samples and lung function tests were performed regularly. Quality of life was assessed by the short-form health survey (SF-36) questionnaire. Results:  Following treatment with adalimumab, FDG-PET uptake decreased in nine patients (P = 0.011) and increased in one patient. Maximum SUV fell from median 14.1 to 7.0 (P < 0.03), and mean SUV fell from median 6.5 to 2.9 (P < 0.02). Six patients had uptake in the lungs, which decreased after treatment (P = 0.035). Six patients had uptake in the lymph nodes, which decreased after treatment in five patients (P = 0.035). Four patients had non-lymphatic extrathoracic uptake, which decreased after treatment (P = 0.05). There was no effect of adalimumab on pulmonary function tests, serum angiotensin I converting enzyme and blood lymphocyte (CD3+, CD4+, CD8+) concentrations. Physical component summary score (SF-36) increased during treatment, mental component summary score was unchanged. Conclusion:  In sarcoidosis, treatment with adalimumab can reduce disease activity, as assessed by FDG-PET. Please cite this paper as: Milman N, Graudal N, Loft A, Mortensen J, Larsen J and Baslund B. Effect of the TNF-α inhibitor adalimumab in patients with recalcitrant sarcoidosis: a prospective observational study using FDG-PET. Clin Respir J 2012; DOI:10.1111/j.1752-699X.2011.00276.x.
  The Clinical Respiratory Journal 11/2011; 6(4):238-47. · 1.06 Impact Factor
• Article: On publication policy and combination therapy.

  Niels Graudal
  Arthritis & Rheumatism 06/2011; · 7.87 Impact Factor
• Article: The sodium phantom.

  Niels Graudal, Gesche Jürgens
  BMJ (Clinical research ed.). 01/2011; 343:d6119; author reply d6121.
• Article: [Biological first-choice preparations in Region H].

  Niels Graudal, Søren Jacobsen, Bo Baslund, Gesche Jürgens
  Ugeskrift for laeger 11/2010; 172(45):3127.
• Article: Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons.

  Niels Graudal, Gesche Jürgens
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  ABSTRACT: To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents. Randomized controlled trials in RA patients, investigating the effects of drug treatment on the percentage of the annual radiographic progression rate (PARPR) were included in a meta-analysis performed with the use of Review Manager 5.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Data from 70 trials (112 comparisons, 16 interventions) were summarized in 21 meta-analyses. Compared with placebo, the PARPR was 0.65% smaller in the single-DMARD group (P < 0.002) and 0.54% smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62% smaller in the combination-DMARD group (P < 0.001) and 0.61% smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001). The effect of a combination of 2 DMARDs plus step-down glucocorticoids did not differ from the effect of a biologic agent plus MTX (percentage mean difference -0.07% [95% confidence interval -0.25, 0.11]) (P = 0.44). Treatment with DMARDs, glucocorticoids, biologic agents, and combination agents significantly reduced radiographic progression at 1 year, with a relative effect of 48-84%. A direct comparison between the combination of a biologic agent plus MTX and the combination of 2 DMARDs plus initial glucocorticoids revealed no difference. Consequently, biologic agents should still be reserved for patients whose RA is resistant to DMARD therapy. Future trials of the effects of biologic agents on RA should compare such agents with combination treatments involving DMARDs and glucocorticoids.
  Arthritis & Rheumatism 10/2010; 62(10):2852-63. · 7.87 Impact Factor
• Article: Dietary salt reductions and cardiovascular disease.

  Niels Graudal, Gesche Jürgens
  New England Journal of Medicine 06/2010; 362(23):2225; author reply 2225-6. · 53.30 Impact Factor
• Article: An HLA study in 74 Danish haemochromatosis patients and in 21 of their families

  Nils Milman, Niels Graudal, Lillian Staub Nielsen, Kirsten Fenger
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  ABSTRACT: Milman N, Graudal N, Nielsen LS, Fenger K. An HLA study in 74 Danish haemochromatosis patients and in 21 of their families. Clin Genet 1992: 41: 6–11HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc <0.001); B7: 33.1% vs. 15.6% (Pc <0.001): B14: 6.9% vs. 3.0% (Pc >0.05); B38: 5% vs. 0.9% (Pc >0.05); B47: 4.0% vs. 0.4% (Pc >0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc <0.001); A3,B7: 25.6% vs. 6.6% (Pc= 0.001); A3,BI4: 3.4% vs. 0.6% (Pc >0.05); A3,B47: 6.9% vs. 0.2% (Pc >0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3, B14 dominated.
  Clinical Genetics 06/2008; 41(1):6 - 11. · 3.13 Impact Factor
• Article: Coexistent pseudohypoparathyroidism and D brachydactyly in a family

  Niels Graudal, Nils Milman, Lillian Staub Nielsen, Erik Niebuhr, Jan Bonde
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  ABSTRACT: The occurrence of pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PH/PPH) and D brachydactyly (DB) in different persons in the same family is described for the first time. The theory that PH/PPH, E brachydactyly (EB), acrodysostosis (AD) and DB are variable expressions of the same trait or allelic traits is proposed. It is advised that newborn babies in such families are investigated carefully in order to exclude hypocalcemic PH. It is suggested that EB is subdivided into 4 groups (Ei-E4) according to the degree of symptoms.The proband of this family was a unique case. In addition to normocalcemic PH she also suffered from hemochromatosis, another rare hereditary disease and she had an abnormal chromosome 20, not earlier described. Both findings were supposed to be coincidental.
  Clinical Genetics 04/2008; 30(6):449 - 455. · 3.13 Impact Factor
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  Article: Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

  Julia S Johansen, Nils Milman, Michael Hansen, Charly Garbarsch, Paul A Price, Niels Graudal
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  ABSTRACT: YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological diagnosis of pulmonal sarcoidosis. Immunohistochemical staining for YKL-40 antigen was performed in five biopsies with pulmonary sarcoid lesions. Serum YKL-40 was likewise measured in 173 healthy age-matched control subjects. Mononuclear cells/macrophages and giant cells in pulmonary sarcoid granulomas expressed YKL-40 protein. Serum YKL-40 was higher in patients with pulmonary sarcoidosis compared to controls (P<0.001) and 63% had elevated serum YKL-40. There was a positive correlation between serum YKL-40 and serum angiotensin converting enzyme (rho=0.55, P=0.0053). Patients with serum YKL-40>median value in the patient group had lower carbon monoxide diffusion capacity corrected for alveolar volume (DLCO/VA) than patients with serum YKL-40 the median value (P=0.015). Conclusions: Serum YKL-40 may be a novel biomarker of sarcoid disease activity and ongoing fibrosis in patients with pulmonary sarcoidosis.
  Respiratory Medicine 04/2005; 99(4):396-402. · 2.47 Impact Factor
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  Available from: Nils Milman

  Article: Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women.

  Nils Milman, Thomas Bergholt, Lisbeth Eriksen, Keld-Erik Byg, Niels Graudal, Palle Pedersen, Jens Hertz
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  ABSTRACT: To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy. A randomized, double-blind intention-to-treat study comprising 427 healthy pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n = 105), 40 mg (n = 108), 60 mg (n = 106), and 80 mg (n = 108) from 18 weeks of gestation. Iron status markers [hemoglobin (Hb), serum ferritin, and serum soluble transferrin receptor (sTfR)] were measured at 18 weeks (inclusion), 32 weeks, and 39 weeks of gestation and 8 weeks postpartum. Side effects of iron supplements were recorded. Iron deficiency was defined as serum ferritin <13 microg/l and iron deficiency anemia as serum ferritin <13 microg/l and Hb <5th percentile in iron replete pregnant women. There were no significant differences between variables in the four groups at inclusion. At 32 and 39 weeks of gestation, group 20 mg had significantly lower median serum ferritin (13 and 16 microg/l) than group 40 mg (17 and 21 microg/l), group 60 mg (18 and 23 microg/l), and group 80 mg (21 and 24 microg/l) (p < 0.0001). At 32 and 39 weeks of gestation, group 20 mg had a significantly higher prevalence of iron deficiency (50 and 29%) than group 40 mg (26 and 11%), group 60 mg (17 and 10%), and group 80 mg (13 and 9%) (p < 0.001). The prevalence of iron deficiency anemia at 39 weeks of gestation was significantly higher in group 20 mg (10%) than in group 40 mg (4.5%), group 60 mg (0%), and group 80 mg (1.5%) (p = 0.02). At 32 weeks of gestation, mean Hb in group 20 mg was lower than in group 80 mg (p = 0.06). There were no significant differences in iron status (ferritin, sTfR, and Hb) between group 40, 60, and 80 mg. Postpartum, group 20 mg had significantly lower median serum ferritin than group 40, 60, and 80 mg (p < 0.01). The prevalence of postpartum iron deficiency anemia was low and similar in the four groups. The frequency of gastrointestinal symptoms was not significantly different in the four iron supplement groups and thus not related to the iron dose. In Danish women, a supplement of 40 mg ferrous iron/day from 18 weeks of gestation appears adequate to prevent iron deficiency in 90% of the women and iron deficiency anemia in at least 95% of the women during pregnancy and postpartum.
  Acta Obstetricia Et Gynecologica Scandinavica 03/2005; 84(3):238-47. · 1.77 Impact Factor
• Article: The natural history and prognosis of rheumatoid arthritis: association of radiographic outcome with process variables, joint motion and immune proteins.

  Niels Graudal
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  ABSTRACT: The purposes of the present study were: 1) to investigate how the long-term course of outcome and inflammatory variables could be described in individual patients and suitably summarized in groups of patients; 2) to investigate the associations between outcome and inflammatory variables on the basis of the defined summary measures; and 3) to investigate new prognostic aspects of RA by means of frozen sera and DNA specimens. During the period 1966-78, 685 Danish Caucasian patients with RA, classified according to the 1958 American Rheumatism Association (ARA) criteria, were admitted to the Department of Rheumatology of Aarhus University Hospital. For scientific purposes all patients went through the same examination programme, including biochemical variables, clinical evaluation of 68 diarthrodial joints, and radiographic evaluation of 46 diarthrodial joints. Since 1987, data from these patients have been organized in a database. The data are arranged according to onset of disease. This thesis is based on about 600,000 data-points from 257 patients. The thesis is based on six studies. The first study shows that early symptomatic improvement of RA during gold treatment was stable over several years, but when evaluated radiographically, the condition continued to deteriorate. In the second study, six main types of radiographic progression were identified: (a) a rare type with no radiographic progression at all (<1%); (b) a type with a slow or moderate onset, but an increasing progression rate (exponential growth type) (9%); (c) a linear type (30%); (d) a type with a moderate to fast onset, and a stable progression rate (the square root type) (11%); (e) a type with a fast onset, but a later decreasing progression rate (the first order kinetics type) (30%) and (f) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type) (20%). The fact that there was a systematic progression was used to define a system of radiographic events, which could be used as outcome measures in prediction models of the long-term course of RA. The third study shows that low serum levels of the complement-activating serum lectin, mannan (mannose) binding protein (lectin) (MBP = MBL), are associated with a higher erythrocyte sedimentation rate (ESR) (p=0.006), joint swelling score (JS score) (p=0.019), limitation of joint motion score (LM score) (p=0.027), and annual increase in radiographic destruction score (R score) (p=0.053). The fourth study demonstrated a highly significant association between summary measures of inflammatory variables and radiographic outcome, as defined in the second study, indicating that the degree of inflammation is important for the development of destructive joint damage in RA. The fifth study showed that MBL-insufficient patients (two defective structural MBL alleles, or one defective allele combined with a low-expression variant of the normal allele) had a relative risk of a severe radiographic event of 3.1 compared with the MBL competent group (p<0.0001). The sixth study showed that the relative risk (RR) of early interleukin (IL)-1alpha auto-antibodies (aAb) positive patients developing serious radiographic joint destruction was significantly lower than for IL-1alpha aAb-negative patients, RR=0.29 (p=0.04). In rheumatoid factor (RF) positive patients RR was only 0.18 (p=0.02). Patients who seroconverted >2 years after the onset of RA showed the most aggressive development of joint erosion, with RR of serious radiographic joint destruction of 2.56 (p=0.048). Other factors investigated in subgroups of the patients were HLA-DR4, chemokine receptor 5 (CCR 5) genotypes. IL-6 aAb, vascular endothelial growth factor (VEGF) aAb, and interferon (IFN)-gamma aAb. About 80% of the patients were HLA-DR4 positive, indicating the importance of HLA-DR4 as a predisposing factor for RA. There was no association between IL-6 aAb and radiographic outcome, or CCR5 genotypes and radiographic outcome. VEGF aAb and IFN-gamma aAb were quantitatively unimportant. In spite of a general improvement in single measures of inflammatory variables, and a general deterioration in radiographic outcome of RA, there is a highly significant association between summary measures of inflammatory variables and radiographic outcome. The progression of radiographic damage in RA follows mathematical patterns. A new method of evaluating the long-term radiographic outcome by means of Kaplan-Meier plots is demonstrated. It is shown that MBL and IL-1alpha aAb are predictors of the prognosis of RA and may play important roles in the pathogenesis of RA.
  Scandinavian journal of rheumatology. Supplement 01/2004; 118:1-38.
• Article: Subgroup results in the DASH-sodium trial.

  Gesche Jürgens, Niels Graudal
  Annals of internal medicine 12/2002; 137(9):772-3; author reply 772-3. · 16.73 Impact Factor
• Article: Plasma vitamin D-binding protein (GC) factors, immunoglobulin G heavy chain (GM) allotypes and immunoglobulin kappa light chain (KM1) allotype in patients with sarcoidosis and in healthy control subjects.

  Nils Milman, Mariann Thymann, Niels Graudal, Niels Morling
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  ABSTRACT: Sarcoidosis is an immune disease with abnormalities in the production of vitamin D and immunoglobulins. The aim was to examine whether the distribution of plasma vitamin D-binding protein = group-specific component (GC) allotypes, immunoglobulin G heavy chain (GM) allotypes and immunoglobulin kappa light chain (KM) allotype differed significantly from the distribution in healthy subjects. GC 1S, 1F, 2 allotypes, GM 1, 2, 5 allotypes, and KM1 allotype were assessed in 44 patients with sarcoidosis and in healthy control subjects. There were no significant differences between the frequencies of the GC, GM and KM allotypes in sarcoidosis patients and in control subjects. Furthermore, there was no relationship between the presentation or course of the sarcoid disease and GC, GM or KM allotypes. GC, GM and KMI allotypes do not appear to play any major role in the pathogenesis of sarcoidosis.
  Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 07/2002; 19(2):97-100. · 1.27 Impact Factor
• Article: Iron status in young Danes. Evaluation by serum ferritin and haemoglobin in a population survey of 634 individuals aged 14–23 yr

  Nils Milman, Charlotte Suppli Ulrik, Niels Graudal, Robert Jordal
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  ABSTRACT: Iron status was assessed by serum ferritin and haemoglobin in a population survey comprising 634 randomly selected urban Danes (312 males, 322 females) 14–23 yr old. At all ages, males had significantly higher serum ferritin and haemoglobin values than females. Males: median serum ferritin displayed a steady increase with age from 33 to 109 μg/l (rs=0.53, p<0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin <13 μg/l) was 3.5% at 16–17 yr of age, gradually declining to 0% at 22–23 yr. None of the males had iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 μg/l (rs=0.19, p<0.001). The prevalence of absent iron stores was 12.5% at 16–17 yr of age, declining to 6.6% at 22–23 yr. The prevalence of iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <121 g/l) was 4.7% at 16–17 yr of age, declining to 1.3% at 22–23 yr of age. Compared with surveys in other parts of Scandinavia, young Danes had slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.
  European Journal Of Haematology 02/1997; 58(3):160 - 166. · 2.61 Impact Factor
• Article: Family studies of hereditary hemochromatosis in Denmark and the Faroe Islands

  Nils Milman, Niels Graudal, Lillian Staub Nielsen, Bjørn Mathiassen, Palle Tauris, Birgit Lund, Jørgen Schøler Kristensen, Kirsten Fenger
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  ABSTRACT: Pedigree studies were performed based on one Faroese and four Danish probands with overt idiopathic hemochromatosis (IH). The study consisted of HLA typing and determination of biochemical iron status indicators (serum transferrin saturation, serum ferritin). In total, 130 persons were evaluated. The screening identified 6 homozygous (h/h) subjects with preclinical IH, 46 heterozygous (h/n), and 8 normal (n/n) subjects, while 39 subjects were classified as normal or heterozygous (n/h?). One family demonstrated both a homozygous x heterozygous as well as a heterozygous x heterozygous mating. Recombination between the HLA region and IH locus occurred possibly in three subjects in three different families. The significance of detailed screening in families with probands with IH is discussed.
  Human Genetics 06/1990; 85(2):228-232. · 5.07 Impact Factor
• Article: Acute phase reactants in the elderly

  Nils Milman, Niels Graudal, Hans Christian Andersen
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  ABSTRACT: The erythrocyte sedimentation rate (ESR), plasma fibrinogen, serum orosomucoid, serum α1-antitrypsin and serum haptoglobin were measured in 267 apparently healthy elderly subjects (median age 79 years, range 60–93), and compared to the values in 58 healthy younger subjects (median age 27 years, range 18–50). The acute phase reactants displayed no sex differences, but were significantly higher in elderly than in younger persons (mean ± SD): ESR 13 ± 10 mm/h vs 4 ± 3 mm/h (p < 0.001); fibrinogen 4.35 ± 0.95 g/1 vs 3.33 ± 0.54 g/1 (p < 0.001); orosomucoid 0.68 ± 0.20 g/1 vs 0.60 ± 0.16 g/1 (p <0.01); α1-antitrypsin 2.16 ± 0.38 g/1 vs 1.84 ± 0.43 g/1 (p < 0.001); haptoglobin 1.30 ± 0.50 g/1 vs 1.00 ± 0.30 g/1 (p < 0.001). Correlations existed between the acute phase reactants, being highest between ESR and fibrinogen (r = 0.53, p < 0.001).
  Clinica Chimica Acta 09/1988; · 2.54 Impact Factor