Search

Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.

ObjectiveTo develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3–ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.

Joanna C Robson,1,2 Jill Dawson,3 Peter F Cronholm,4 Nataliya Milman,5 Katherine S Kellom,6 Susan Ashdown,7 Ebony Easley,8 John T Farrar,9 Don Gebhart,10,11 Georgia Lanier,10,11 Carol A McAlear,12 Jacqueline Peck,7 Raashid A Luqmani,7 Judy A Shea,13 Gunnar Tomasson,14 Peter A Merkel10,11 1Department of Rheumatology, Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK; 2School of Clinical Sciences, University of Bristol, Bristol, UK; 3Department of Population Health (HSRU), University of Oxford, Oxford, UK; 4Department of Family Medicine and Community Health, University of Pennsylvania, Philadelphia, PA, USA; 5Division of Rheumatology, Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada; 6PolicyLab, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 7Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 8Department of Family Medicine and Community Health, Mixed Methods Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; 9Biostatistics and Epidemiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 10Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 11Department of Biostatistics and Clinical Epidemiology, University of Pennsylvania, Philadelphia, PA, USA; 12Vasculitis Research, University of Pennsylvania, Philadelphia, PA, USA; 13School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 14Department of Public Health Sciences, University of Iceland, Reykjavik, Iceland Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients.Methods: Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation.Results: Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items.Conclusion: This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire. Keywords: ANCA-associated vasculitis, quality of life, patient-reported outcomes, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis

Lillian Barra,1 Patrick Liang,2 Susanne M Benseler,3 David A Cabral,4 Aurore Fifi-Mah,5 Yueyang Li,1 Nataliya Milman,6 Marinka Twilt,3 Elaine Yacyshyn,7 Christian Pagnoux8 1Division of Rheumatology, The University of Western Ontario, St Joseph’s Health Care, London, Ontario, 2Division of Rheumatology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, 3Division of Rheumatology, Department of Paediatrics, Alberta Children’s Hospital, University of Calgary, Calgary, Alberta, 4Division of Rheumatology, BC Children’s Hospital, Vancouver, British Columbia, 5Division of Rheumatology, South Health Campus, University of Calgary, Calgary, Alberta, 6Division of Rheumatology, Department of Medicine, University of Ottawa, Ottawa, 7Division of Rheumatology, University of Alberta, Edmonton, Alberta, 8Department of Rheumatology, Mount Sinai Hospital, Toronto, University of Toronto, Ontario, Canada Objective: Takayasu arteritis (TAK) is a large vessel vasculitis that predominately affects young women and can cause severe ischemic complications. Given the rarity of TAK, the management of this condition is challenging. We aim to describe current rheumatologist practices for the management of TAK and identify discrepancies and gaps in knowledge. Methods: An online survey (developed by the Canadian Vasculitis Network and approved by the Canadian Rheumatology Association) containing 48 questions with regard to the diagnosis, monitoring and treatment of TAK was distributed to 495 Canadian adult and pediatric rheumatologists by email. Results: Sixty-six rheumatologists completed the survey (13% response rate): the majority (73%) were from academic centers and ≤25% reported managing more than ten patients in their career. For establishing the diagnosis of TAK, they relied on a combination of signs and symptoms of ischemia, elevations of inflammatory markers and vascular imaging (typically computed tomography and magnetic resonance angiography). The frequency of monitoring for disease activity and the methods employed (clinical, laboratory or imaging) were variable. All physicians used corticosteroids for the treatment of TAK, but 42% would treat for at least 6–12months, 26% for 12–24 months and 23% would never stop corticosteroids. Fifty-three percent would always use an immunosuppressant (most commonly methotrexate or azathioprine) in addition to corticosteroids and the remainder would only start an immunosuppressant in patients with refractory or relapsing disease. Conclusion: Physician practices for the management of TAK are variable, suggesting that there are knowledge gaps, which may impact outcomes in patients with TAK. Keywords: Takayasu arteritis, physician practice patterns, practice guidelines, large vessel vasculitis, aortitis

Objective.The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis.Methods.Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments from 10 PROMIS item banks were selected with direct involvement of patients. Subjects completed PROMIS instruments using computer adaptive testing (CAT). The Medical Outcomes Study Short Form-36 (SF-36) was also administered. Cross-sectional construct validity was assessed by calculating correlations of PROMIS scores with SF-36 measures and physician and patient global scores for disease activity. Longitudinal construct validity was assessed by correlations of between-visit differences in PROMIS scores with differences in other measures.Results.During the study period, 973 subjects came for 2306 study visits and the PROMIS collection was completed at 2276 (99%) of visits. The median time needed to complete each PROMIS instrument ranged from 40 to 55 s. PROMIS instruments correlated cross-sectionally with individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. For example, PROMIS fatigue correlated with both the physical component score (PCS; r = −0.65) and with the mental component score (MCS; r = −0.54). PROMIS physical function correlated strongly with PCS (r = 0.81) but weakly with MCS (r = 0.29). Weaker correlations were observed longitudinally between change in PROMIS scores with change in PCS and MCS.Conclusion.Collection of data using CAT PROMIS instruments is feasible among patients with vasculitis and has some cross-sectional and longitudinal construct validity.

International audience; Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the management of anaemia and haematinic deficiencies in pregnancy and in the post-partum period as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, policymaking and epidemiology was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO) and the European Board and College of Obstetrics and Gynaecology (EBCOG). Members of the task force assessed the quantity, quality and consistency of the published evidence and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing the perinatal care of women in all settings and by policymakers in charge of decision making for the update of clinical practice in health-care establishments. They need to be tailored for application in individual patients or any population after consideration of the values and preferences of both health-care providers and patients, as well as equity issues; explicit assessment of harms and benefits of each recommendation; feasibility including resources, capacity and equipment; and implementability.

Item does not contain fulltext

PubMedID: 28864648 Objective. To arrive at consensus for candidate outcomes for disease activity assessment in largevessel vasculitis (LVV) in clinical trials. Methods.A Delphi survey including 99 items was circulated among international experts for 3 rounds. Results. Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. Conclusion. This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes. Copyright © 2017. All rights reserved. National Institute of Arthritis and Musculoskeletal and Skin Diseases: U01 AR51874 04, U54 AR057319 National Center for Research Resources: U54 RR019497 Sponsored by the Vasculitis Clinical Research Consortium, which has received support from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. Additional support for the work of the OMERACT Vasculitis Working Group was received through a Patient-Centered Outcomes Research Institute Pilot Project Grant. S.Z. Aydin, MD, Associate Professor, Division of Rheumatology, The Ottawa Hospital Research Institute, University of Ottawa; H. Direskeneli, MD, Professor of Rheumatology, Division of Rheumatology, Marmara University Faculty of Medicine; P.A. Merkel, MD, MPH, Professor of Medicine and Epidemiology, Division of Rheumatology, and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania. Address correspondence to Dr. P.A. Merkel, Section of Rheumatology, University of Pennsylvania, White Building, 5th Floor Penn, 3400 Spruce St., Philadelphia, Pennsylvania 19104, USA. E-mail: pmerkel@upenn.edu Accepted for publication June 3, 2017.

ObjectiveThe International Classification of Functioning, Disability and Health (ICF) is a framework and classification of health that describes health along 4 components: body functions, body structures, activities and participation, and contextual factors. This study examined the content of instruments that constitute the Outcome Measures in Rheumatology (OMERACT) core set of outcome measures for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) by mapping them to the ICF. MethodsThe content of the instruments included in the AAV core set were linked to the ICF by 2 independent investigators according to previously established ICF linkage rules. ResultsThe AAV core set includes 3 measures of disease activity (3 versions of the Birmingham Vasculitis Activity Score), 1 damage measure (Vasculitis Damage Index), 1 patient-reported outcome (Short Form 36 health survey), and death. Linking these instruments to the ICF revealed comprehensive coverage of the ICF components body functions and body structures, limited coverage of the ICF component activities and participation, and complete absence of coverage of contextual factors. ConclusionICF was found to be useful for thematic characterization of a heterogeneous group of outcome measures for AAV, i.e., a group of complex medical conditions. Linking of the instruments selected for the OMERACT AAV core set of outcome measures to the ICF classification revealed limitations in the representation of constructs related to life impact of AAV, represented by the ICF components activities and participation and contextual factors. Further research and methods development are needed to better incorporate important aspects of functioning and health relevant to patients into clinical trials of AAV.

The purpose of this study was to measure the content of iron (Fe) in liver tissue samples from urbanized Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver tissue samples from urbanized Danes. Normal liver tissue samples were obtained at autopsy from 50 Greenlandic Inuit (27 men, 23 women) with a median age of 61 years (range 23-83) and from 72 Danes (42 men, 30 women) with a median age of 62 years (range 15-87). In the entire series, there was no significant difference between liver iron in Inuit compared with Danes. Likewise, there was no significant gender difference concerning liver iron content, either in Inuit or in Danes. The median iron content (with 5-95 percentile) in Inuit was 17.23 mmol/kg dry liver (5.80-91.80) and in Danes 16.51 mmol/kg dry liver (7.83-39.05). However, when stratified according to age, a trend was revealed showing that Inuit men and womenor = 50 years had a lower liver iron content than Danes (p = 0.05 and p = 0.08) whereas Inuit men and women50 years had a higher liver iron content than Danes (p = 0.18 and p = 0.02). There was a significant correlation between liver iron content and age in both Inuit men (rs = 0.49, p = 0.01) and in women (rs = 0.64, p = 0.003), but not in Danes. In Inuit, the median hepatic iron index (liver iron content divided by age) was 0.33 in men and 0.32 in women. The median estimated iron content in the whole liver was 6.54 mmol (365 mg) in Inuit men and 5.41 mmol (302 mg) in Inuit women (p = 0.6). There was no correlation between hepatic iron index and age. In Danes, the median hepatic iron index was 0.46 in men and 0.29 in women (p = 0.01). There was a significant inverse correlation between hepatic iron index and age in the two genders and in the entire series (rs = -0.71, p = 0.0001). The results indicate that young and middle-aged urbanized Inuit have slightly smaller iron stores than urbanized Danes, whereas elderly Inuit have higher iron stores than Danes. In Danes, iron stores plateau at 30 to 40 years of age in men and some years after the menopause in women. In Inuit, iron stores continue to increase in old age, probably to due a lifelong dietary intake of haem iron.

In Denmark, the number of women in reproductive age havingRoux-en-Y gastric bypass surgery increased in the period 2007-2010. The malabsorption related to the operation implies apredisposition to macro- and micronutrient deficiencies, whichin pregnancy may influence the development of the foetus. Thearticle concerns the need for managing the malabsorptionsyndrome, iron deficiency in particular, both in antenatal care,during pregnancy, delivery and in the lactation period. Wesuggest frequent follow-up in these patients and intravenousiron therapy, when oral iron treatment is inadequate.

Juvenile haemochromatosis caused by a homozygous Gly320Val mutation in the haemojuvelin (HJV) gene was diagnosed in a 12-year-old Danish girl and her 10-year-old sister. Both appeared healthy without clinical or biochemical signs of organ damage. They had iron overload (plasma transferrin saturation 81 and 80%, plasma ferritin 3,671 and 1,356 microgram/l, liver iron content of 375 and 361 micromol/g dry weight, normal myocardial iron content. Their parents were both HJV heterozygous with normal iron status. The girls began phlebotomy treatment with favourable effect.

Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP.

OBJECTIVE: To compare haemoglobin concentrations in Greenlanders and Danes.METHODS: Haemoglobin was measured in a population survey in 1993-1994 comprising 234 indigenous Greenlandic individuals (115 men) aged 19-82 yr. and in Copenhagen County 1983-1984 comprising 2804 Caucasian Danes (1444 men) aged 30-60 yr. The Greenlandic participants were residents in the capital Nuuk (n=70), the town Ilulissat (n=74), and four settlements in the Uummannaq district (n=90). The significance of differences was assessed by Student's t-test, and the xi2-test. Correlations were assessed by Spearman's correlation coefficient (rs).RESULTS: Greenlanders: Haemoglobin levels were not correlated with age or consumption of traditional foods, and were not significantly different in the three residential areas. Mean haemoglobin was higher in men, 146+/-9.6 (SD) g/L, than in women, 132+/-9.6 g/L (p32 microg/L (n=104) was 146+/-9.3 g/L, and in iron-replete women (n=68) 133+/-10.4 g/L (p50 yr of age. Danes: Mean haemoglobin in men was 154+/-10.0 g/L and in women 138+/-10.4 g/L (p32 microg/L) was 154+/-10.7 g/L, and in iron-replete women (n=1003) 140+/-9.6 g/L (p50 yr of age.CONCLUSION: Haemoglobin concentrations in Greenlanders were significantly lower than in Danes both in men (p

OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic individuals (109 men) aged 19-82 yr. The participants were residents in the capital Nuuk (n=73) with a predominantly Western style of living, the town Ilulissat (n=60) with a mixture of Western and Greenlandic style of living, and the small town Uummannaq (n=91) with a predominantly Greenlandic style of living. Consumption of traditional foods was assessed by questionnaire.RESULTS: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p200 microg/L) was lowest in Nuuk (men: 13.8%, women: 2.3%) intermediate in Ilulissat (men, 11.1%; women, 9.1%) and highest in Uummannaq (men, 32.1%; women, 21.1%). The prevalence of iron depletion (ferritin CONCLUSION: The observed differences in estimated body iron stores in Greenlanders from the three residential areas can be explained by differences in the dietary intake of haem iron.

We evaluated the influence of Helicobacter pylori (H. pylori) infection assessed by the levels of H. pylori serum IgG-antibodies, on iron status (serum ferritin and haemoglobin) in 2794 Danes (1425 men), aged 30-60 years. The seroprevalence of H. pylori antibodies increased with age (p0.01). Median serum ferritin levels were significantly lower in seropositive than in seronegative men and postmenopausal women (men 114 micrograms/L vs. 120 micrograms/L, p = 0.01; premenopausal women 37 micrograms/L vs. 40 micrograms/L, p = 0.13; postmenopausal women 63 micrograms/L vs. 77 micrograms/L, p = 0.02). Seropositive subjects had a higher prevalence of iron deficiency (serum ferritin15 micrograms/L) than seronegative subjects. H. pylori infection has a negative influence on iron status. We hypothesize that this may be caused by increased blood losses from the gastric mucosa.

Chlamydia pneumoniae (C.pn.) is claimed to be of importance for the development of bronchial asthma in previously healthy individuals. This is a new and speculative theory. Earlier studies have mainly focused on C.pn. and exacerbation of asthma. If this new theory were true, one would expect titres of C.pn.-specific IgG to be higher or more common in patients compared with controls. It would also seem probable that pathobiological mechanisms as found in connection with other microorganisms could be demonstrated, i.e. presence of C.pn.-specific IgE and the capability of C.pn. to induce or enhance histamine release from basophil leukocytes. We therefore examined C.pn.-specific IgE, IgG and IgM in sera from 22 adults with bronchial asthma and 25 healthy controls. IgE was verified by passive sensitization of basophils from umbilical cord blood. The prevalence of IgE was approx. 69% and IgG approx. 23% in both groups. IgG-titres were between 1:16 and 1:64 in both groups. No IgM was found. Further, C.pn. could neither induce nor enhance histamine release from basophil leukocytes of patients or controls. We conclude that patients with bronchial asthma and healthy controls do not differ in relation to 1) C.pn.-specific IgE in sera, 2) the capability of C.pn. to induce or enhance histamine release from basophil leukocytes, since no such effect was found, or 3) previous C.pn. infection judged by the presence of specific IgG antibodies. Our results cannot support the theory that C.pn. is a cause of adult-onset asthma.

Iron status was assessed by measuring serum ferritin and haemoglobin in a population survey in Copenhagen County, comprising 1359 nonpregnant women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal. Premenopausal women had lower serum ferritin (median 37 micrograms/l) than postmenopausal women (median 71 micrograms/l), p0.0001. Of premenopausal women, 17.7% had ferritin15 micrograms/l (depleted iron stores), and 23.1% had ferritin levels of 15-30 micrograms/l (small iron stores). Corresponding figures in postmenopausal women were 3.3% and 10.3%. Iron deficiency anaemia (ferritin15 micrograms/l and haemoglobin121 g/l) was observed in 2.6% of pre- and 0.36% of postmenopausal women. After menstruations had ceased, there was a steep rise in ferritin levels, being most pronounced during the first 7 postmenopausal years. Pre- and postmenopausal multipara had lower ferritin than nulli- and unipara (p0.04), indicating that pregnancy and childbirth had a long lasting reducing influence on iron stores. The use of oral hormonal contraceptives had a marked increasing effect on iron stores, being correlated to the number of years the women had been taking the pill.

Bone marrow haemosiderin iron grade and serum (S-) iron status markers (haemoglobin (Hb), S-iron, S-transferrin, transferrin saturation, S-ferritin) were measured in 31 patients with newly discovered small cell cancer of the lung (SCCL), and compared to the values in 53 healthy control subjects. Among SCCL patients, 2 had grade 0 (absent), 5 grade (1+) (trace), 8 grade 1+ (normal), and 16 grade 2+ (increased) marrow haemosiderin iron. Median S-ferritin values in the respective groups were 38 mug/l, 243 mug/l, 384 mug/l and 433 mug/l. There was no correlation between Hb, S-iron, S-transferrin or transferrin saturation and marrow iron grade. S-ferritin displayed a correlation with marrow iron grade (r(s) = 0.40, p

The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e. by L. pneumophila multiplying intracellularly. In this study, L. pneumophila was demonstrated to produce protease in guinea-pig and human alveolar macrophages infected in vitro. After 24 h infection, approximately 0.1 to 0.2 micrograms of protease per 10(6) bacteria was measured by ELISA in culture supernatants and lysates of the infected cells, whereas no protease could be detected immediately after infection. Immunogold labelling using anti-protease antibody showed the enzyme to be located within phagosomes and distributed throughout the macrophages. Recent observations have shown that this protease could modify host defence mechanisms through inhibition of bacterial killing by neutrophils and monocytes. The intracellular production of the enzyme in infected macrophages demonstrated here further supports a role for the protease in the pathogenesis of Legionnaires' disease.

Various elements (K, Fe, Cu, Zn, Br) were measured by X-ray flourescence spectrometry in cellular and connective tissue fractions of normal and cirrhotic liver samples obtained at autopsy. Normal livers: 32 subjects (16 males, 16 females) median age 69 years. Cirrhotic livers: 14 subjects (13 males, 1 female) with alcoholic cirrhosis, median age 55 years. Cellular and connective tissue fractions were separated by blending and sieving of the liver samples. Normal livers:K, Cu and Zn content was higher, and Br content lower in the cellular than in the connective tissue fractions. Median values in cellular/connective tissue fractions in mmol/kg/dry weight were: K, 121.04/48.67, p

Udgivelsesdato: 1990-Jan Haemophilus influenza and its extracellular products (EP) did not release histamine from basophil leukocytes in cell suspensions from normal individuals, patients with chronic bronchitis or patients allergic to either house dust mite, grass pollen, cat dander or to their own bacteria. However, the EP was found to enhance their basophil histamine release. IgE-mediated histamine release was examined by stimulation of the cells with anti-IgE or the specific allergens, and non-immunological histamine release by stimulating the cells with the calcium ionophore A23187 or Staphylococcus aureus. In all the experiments EP caused a significant increase in the histamine release. When H. influenzae endotoxins were removed from the EP, the potentiating effect of EP was completely abolished, whereas heating (80 degrees C, 30 min) or treatment of EP with proteinase did not influence the potentiating effect. These results indicate that H. influenzae endotoxin potentiates histamine release caused by IgE-mediated reactions or by non-immunological mechanisms.

Iron stores were evaluated by serum ferritin determinations in 948 menstruating and 141 non-menstruating female blood donors. Blood donation was associated with a decrease in ferritin. First-time donors (n = 163) had a geometric mean ferritin of 24 micrograms/l and multiple-time donors a value of 19 micrograms/l (p less than 0.01). In the donating population 31.5% had ferritin values less than 15 micrograms/l (i.e. depleted iron stores). Menstruating donors had lower mean serum ferritin than non-menstruating donors (p less than 0.001), and a higher frequency of ferritin values less than 15 micrograms/l (p less than 0.05). There was no relationship between ferritin levels and the number of pregnancies. The frequency of donations was more predictive of ferritin levels than the number of donations. Mean ferritin displayed a moderate fall up to the 2nd donation, and was hereafter relatively constant, whereas an increase in donation frequency was accompanied by a significant decrease in ferritin. Female donors, especially when phlebotomised greater than or equal to 3 times per year, should have their iron status checked at appropriate intervals by measurement of serum ferritin and should be advised regular iron supplementation.

The synovial fluid ferritin level in 49 patients (57 joints) with various rheumatic diseases was analysed. In rheumatoid arthritis (n = 22) the geometric mean ferritin level was 528 micrograms/l (range 56-3 100 micrograms/l), in other inflammatory arthritides (n = 12) 339 micrograms/l (105-2 835 micrograms/l) (p greater than 0.5), in calcium pyrophosphate arthropathy (n = 14) 507 micrograms/l (180-4 230 micrograms/l) (p greater than 0.5) and in non-inflammatory osteoarthritis (n = 9) 167 micrograms/l (14-725 micrograms/l) (p less than 0.05). Synovial fluid/serum ferritin ratios did not differ significantly in the four diagnostic groups; 4 patients had ratios less than 1.0. Synovial fluid ferritin was not correlated to total fluid cell count or differential cell count. Although ferritin content was significantly greater in inflammatory than in noninflammatory fluid (p less than 0.05), the wide scatter of the values and marked overlap between the different groups limit the value of measuring synovial fluid ferritin as a differential diagnostic test for rheumatic diseases.

Serum ferritin and biochemical liver tests (serum bilirubin, serum aspartate transaminase, serum gamma-glutamyl transpeptidase (gamma-GT), and serum alkaline phosphatase) were recorded at regular intervals from admission to recovery in six patients with acute viral hepatitis. There was a proportional, significant decrease in ferritin bilirubin, and transaminase were reached simultaneously, whereas gamma-GT and alkaline phosphatase remained elevated for a slightly longer time. The correlations between corresponding measurements of ferritin and biochemical liver tests were as follows: ferritin and alkaline phosphatase, r = 0.72, P less than 0.001; ferritin and bilirubin, r = 0.68, P less than 0.001; ferritin and transaminase, r = 0.53, P less than 0.001; ferritin and gamma-GT. r = 0.50, P less than 0.001. In viral hepatitis serum ferritin offers no diagnostic advantage compared with already established tests for hepatocellular damage.

To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA).In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints.An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak.A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that iron-treated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebo-treated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 60-70 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.

Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae) and Branhamella catarrhalis (B. catarrhalis) are often found in the lower respiratory tract of patients with chronic bronchitis. Earlier studies have shown that bacteria induce mediator release from human basophils and parenchymal lung mast cells. In this study the capability of bacteria to trigger or potentiate histamine release from superficially located mast cells in the airway epithelium was studied in cell suspensions obtained by bronchoalveolar lavage in patients with chronic bronchitis (CB). In approximately half of the patients H. influenzae and Staphylococcus aureus (S. aureus) were found to trigger histamine release, whereas no response was obtained by S. pneumoniae or B. catarrhalis. The mediator release was caused by a non-IgE-dependent mechanism. At lower concentrations of H. influenzae causing no histamine release the bacterium was found to enhance IgE-mediated histamine release triggered by anti-IgE antibody. The synergy was more pronounced in patients with CB than in controls. Since H. influenzae is found in the lower respiratory tract of the patients but not in normal individuals, the infection here may via histamine release lead to harmful effects on the airways of importance for precipitation and exacerbation of chronic bronchitis.

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles.