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1.
J Air Transp Manag ; 99: 102175, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34876782

ABSTRACT

Transmission of SARS-CoV-2 between passengers on airplanes is a significant concern and reducing the transmission of SARS-CoV-2 or other viruses aboard aircraft could save lives. Solving the Airplane Seating Assignment Problem (ASAP) produces seating arrangements that minimize transmission risks between passengers aboard an aircraft, but the chosen risk model affects the optimal seating arrangement. We analyze previous risk models and introduce two new risk models, masked and unmasked, based on previous experiments performed aboard real aircraft to test aerosol dispersion of SARS-CoV-2 sized particles. We make recommendations on when each risk model is applicable and the types of seating arrangements that are optimal for each risk model.

2.
Public Health ; 189: 101-103, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33197730

ABSTRACT

OBJECTIVES: The first three months of the COVID-19 pandemic has disrupted healthcare systems, creating an environment by which deaths have occurred that are not directly due to COVID-19, but have occurred owing to the healthcare and societal environment resulting from COVID-19. The objective of this research is to quantify such excess deaths, partitioned by age group and gender. STUDY DESIGN: This is a data analysis. METHODS: Excess deaths by age and gender are estimated using provisional death data available from the Centers for disease control and prevention (CDC) over the time period from March 1, 2020 through May 30, 2020. Previous year fatality and population data are used as the benchmark. RESULTS: Several of the eighteen age and gender cohorts experienced statistically significant excess deaths. The results also indicate that COVID-19 has been protective for one of the age and gender cohorts. CONCLUSIONS: There have been more excess deaths in several age group and gender cohorts during the first three months of the pandemic, beyond direct deaths directly attributable to COVID-19. These non-COVID-19 excess deaths are most apparent in the 25- to 44-year age group for women and 15- to 54-year age group for men. Further research is needed to assess the cause of such excess deaths and introduce safeguards to reduce such deaths in the future.


Subject(s)
COVID-19/epidemiology , Mortality/trends , SARS-CoV-2 , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Centers for Disease Control and Prevention, U.S./statistics & numerical data , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Sex Distribution , United States/epidemiology , Young Adult
3.
J Intern Med ; 288(5): 581-592, 2020 11.
Article in English | MEDLINE | ID: mdl-32638487

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.


Subject(s)
Biomarkers/blood , Myocardial Infarction/complications , Proteomics , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Adrenomedullin/blood , Aged , Female , Growth Differentiation Factor 15/blood , Humans , Male , Middle Aged , Perilipin-2/blood , Receptors, TNF-Related Apoptosis-Inducing Ligand/blood , Receptors, Tumor Necrosis Factor/blood
4.
Public Health ; 128(9): 799-803, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25183564

ABSTRACT

Wearing a seatbelt can prevent motor vehicle crash deaths. While primary seatbelt laws are designed to encourage vehicle passengers to wear seatbelts by allowing law enforcement officers to issue tickets when passengers do not wear seatbelts, discomfort may discourage obese individuals from wearing a seatbelt. The objective of this study is to assess the association between state-level obesity and seatbelt usage rates in the US, and to examine the possible role played by seatbelt laws in these associations. The strength of the association between obesity rates, seatbelt usage, and primary seatbelt laws at the state level is investigated using data from 2006 to 2011. Linear regression analysis is employed. This model estimates that increasing the obesity rate by 1% in a state where a primary seatbelt law (by which law enforcement officers can issue a ticket when seatbelts are not worn) is in effect is associated with a 0.06% decrease in seatbelt usage. However the same percentage of increase in the obesity rate in a state where no primary seatbelt law is in effect is associated with a 0.55% decrease in seatbelt usage. The magnitude of the statistical association between state obesity rates and state-level seatbelt usage is related to the existence of a primary seatbelt law, such that obesity has less impact on seatbelt usage in states where primary seatbelt laws are in effect.


Subject(s)
Automobile Driving/legislation & jurisprudence , Obesity/epidemiology , Seat Belts/legislation & jurisprudence , Seat Belts/statistics & numerical data , Adult , Automobile Driving/statistics & numerical data , Female , Humans , Linear Models , Male , United States/epidemiology
5.
Scand J Immunol ; 78(6): 538-44, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24111715

ABSTRACT

Patients with chronic kidney disease (CKD) display a high prevalence of cardiovascular events and acute infections. Potential effector cells are the CD16(+) monocytes, known to be increased in the peripheral circulation in CKD. The aim of this study was to assess the expression of CD16 and CX3 CR1 on peripheral and in vivo extravasated monocytes in patients with CKD (GFR < 20 ml/min × 1.73 m²) using flow cytometry. In vivo extravasated monocytes were collected from a local inflammatory site, induced by a skin blistering technique. Soluble markers were assessed by Luminex. The number of CD16(+) monocytes was significantly higher in patients with CKD compared with healthy subjects, both in the peripheral circulation (P < 0.05) and at the site of induced inflammation (P < 0.001). Patients with CKD displayed significantly higher concentration of soluble CX3 CL1 both in the peripheral circulation (P < 0.01) and in the interstitial fluid (P < 0.001). In addition, patients with CKD had a significantly higher concentration of TNF-α in the peripheral circulation (P < 0.001). On the contrary, at the inflammatory site, concentrations of both TNF-α and IL-10 were significantly lower in patients with CKD compared with healthy controls (P < 0.05 for both). In conclusion, patients with CKD have an increased percentage of CD16(+) monocytes in both circulation and at the inflammatory site, and this finding is in concurrence with simultaneous changes in CX3 CR1. Together with distorted TNF-α and IL-10 levels, this may have potential impact on the altered inflammatory response in CKD.


Subject(s)
Monocytes/immunology , Receptors, Chemokine/metabolism , Receptors, IgG/immunology , Renal Insufficiency, Chronic/immunology , CX3C Chemokine Receptor 1 , Female , Humans , Inflammation/immunology , Interleukin-10/blood , Male , Middle Aged , Receptors, Chemokine/blood , Receptors, IgG/blood , Tumor Necrosis Factor-alpha/blood
6.
Clin Exp Immunol ; 168(1): 105-12, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22385245

ABSTRACT

In order to address neutrophil activation during inflammation we assessed the expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo extravasation. Extravasated neutrophils were collected from 11 healthy study subjects by a skin chamber technique and compared to neutrophils in peripheral blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following extravasation, demonstrated by both gene array and qPCR. Western blot demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This was confirmed further in neutrophils by flow cytometry and iEM that also demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral neutrophils with IL-1 resulted in transcription of NFκB and a number of downstream chemokines and the corresponding chemokines were also induced following in-vivo extravasation. The present results demonstrate that IL-1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL-1R1 as demonstrated by the induction of chemokines following IL-1 stimulation. The results indicate a potential role for IL-1 in the activation of neutrophils at inflammatory sites.


Subject(s)
Neutrophil Activation , Neutrophils/metabolism , Receptors, Interleukin-1 Type I/biosynthesis , Aged , Chemokines/biosynthesis , Chemokines/genetics , Female , Gene Expression , Humans , Interleukin-1/pharmacology , Interleukin-1alpha/blood , Interleukin-1beta/blood , Male , Middle Aged , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , NF-kappa B/biosynthesis , NF-kappa B/genetics , Neutrophils/immunology , Receptors, Interleukin-1 Type I/blood , Receptors, Interleukin-2/blood , Transcription, Genetic/drug effects
7.
Scand J Immunol ; 75(4): 419-25, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22229891

ABSTRACT

The cellular and soluble mediators of a dermal inflammation can be studied by the skin chamber technique. The aim of this study was to address the physiological effect of soluble mediators, released into the skin chamber, with special focus on neutrophil CD11b activation. Mediators released at the inflammatory site were studied by Milliplex and enzyme-linked immunosorbent assay (ELISA) and correlated with transmigration and CD11b activation in vivo and in vitro. Transmigration was studied by the skin chamber technique and by the transwell method, and expression of the CBRM1/5 epitope on activated CD11b was analysed by flow cytometry following in vivo and in vitro incubation with chamber fluid or recombinant interleukin-8 (IL-8). Leucocyte in vivo and in vitro transmigration both correlated with the concentrations of IL-1ß, tumour necrosis factor alpha (TNFα) and IL-8 at P < 0.05 (R > 0.7). Furthermore, CD11b was activated, in terms of exposure of the activation epitope, on neutrophils after 30 min of in vitro incubation with chamber fluid and correlated solely with the concentration of IL-8, P < 0.05 (R = 0.72). In vitro incubation with recombinant IL-8 confirmed a concentration-dependent expression of the activation epitope; however, induction of CBRM1/5 by recombinant IL-8 required a concentration that was significantly higher compared with that in chamber fluid. In addition, the CBRM1/5 epitope was analysed on in vivo extravasated neutrophils that displayed a significantly higher expression compared with circulating neutrophils, P = 0.04. We conclude that IL-8 is the major factor regulating the expression of CD11b activation epitope in neutrophils.


Subject(s)
Blister/immunology , CD11b Antigen/immunology , Interleukin-8/immunology , Cell Movement , Epitopes/immunology , Female , Humans , Male , Middle Aged , Neutrophils/cytology , Neutrophils/immunology
8.
Scand J Urol Nephrol ; 46(2): 148-55, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22214235

ABSTRACT

OBJECTIVE: Serum levels of the apolipoprotein B/apolipoprotein A-I ratio (ApoB/ApoA-I) have been shown to identify patients at risk of cardiovascular disease. The aim of this study was to evaluate whether raised ApoB/ApoA-I values are also predictive of renal outcome in patients with chronic kidney disease (CKD), as similar mechanisms seem to be involved in the development of atherosclerosis and glomerulosclerosis. Only patients with immunoglobulin A nephropathy (IgAN) were included, since they represent a homogeneous group of patients with CKD. MATERIAL AND METHODS: ApoB and ApoA-I, serum albumin, urine albumin and blood pressure were measured, and a highly sensitive C-reactive protein test was carried out, in 70 patients with IgAN and in 70 age- and gender-matched healthy control subjects. Patients were followed over a period of up to 11 years (median 3.8 years). End-stage renal disease (ESRD) was defined as reaching CKD stage 5 [estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m²]. RESULTS: Baseline ApoB/ApoA-I values greater than 0.9 for men and greater than 0.8 for women were associated with a risk of developing CKD stage 5 (risk ratio 5.7, p = 0.037), independently of baseline GFR and serum albumin. CONCLUSION: Patients with IgAN and an increased ApoB/ApoA-I ratio have a significantly higher risk of developing ESRD compared with patients with a low ratio. Controlled studies are warranted to demonstrate whether interventions focusing on the ApoB/ApoA-I ratio may have beneficial clinical effects.


Subject(s)
Apolipoprotein A-I/blood , Apolipoproteins B/blood , Glomerulonephritis, IGA/blood , Kidney Failure, Chronic/blood , Adult , Albuminuria/metabolism , Blood Pressure , C-Reactive Protein/metabolism , Female , Follow-Up Studies , Glomerular Filtration Rate , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/urine , Humans , Kaplan-Meier Estimate , Kidney Failure, Chronic/etiology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Risk Factors , Serum Albumin/metabolism
9.
Clin Nephrol ; 74(3): 198-208, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20860904

ABSTRACT

AIMS: The pan-European ECHO observational study evaluated cinacalcet in adult dialysis patients with secondary hyperparathyroidism (SHPT) in "real-world" clinical practice. A sub-analysis compared data for 7 European countries/country clusters: Austria, CEE (Czech Republic and Slovakia), France, Italy, Netherlands, Nordics (Denmark, Finland, Norway, and Sweden), and the UK/Ireland. METHODS: Data on serum intact parathyroid hormone (iPTH), phosphorous, calcium, as well as the usage of cinacalcet, active vitamin D analogues and phosphate binders were compared. RESULTS: 1,865 patients (mean age 58 years) were enrolled: median baseline iPTH levels ranged from 605 pg/ml in Austria to 954 pg/ml in the UK/Ireland. After ~1 year of cinacalcet, median iPTH reductions from baseline ranged from 38% in the UK/Ireland to 58% in the Netherlands. The proportion of patients achieving NKF/K-DOQITM iPTH targets (150 - 300 pg/ml) at Month 12 ranged from 14% in the UK/Ireland to 40% in CEE. In general, use of sevelamer decreased, while use of calcium-based phosphate binders increased, during cinacalcet treatment. Vitamin D changes were more variable. CONCLUSION: The iPTH level at which cinacalcet is initiated in clinical practice differs considerably among different countries: where cinacalcet was started at a lower iPTH level this resulted in better achievement of serum iPTH targets.


Subject(s)
Hyperparathyroidism, Secondary/drug therapy , Naphthalenes/therapeutic use , Adult , Aged , Aged, 80 and over , Cinacalcet , Europe , Female , Humans , Hyperparathyroidism, Secondary/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Parathyroid Hormone/blood , Prospective Studies , Renal Dialysis , Retrospective Studies , Treatment Outcome
10.
J Intern Med ; 268(1): 40-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20210836

ABSTRACT

OBJECTIVE: To examine clinical characteristics, presenting symptoms, use of therapy and in-hospital complications in relation to renal function in patients with myocardial infarction (MI). DESIGN: Observational study. SETTING: Nationwide coronary care unit registry between 2003-2006 in Sweden. SUBJECTS: Consecutive MI patients with available creatinine (n = 57,477). RESULTS: Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease Study formula. With declining renal function patients were older, had more co-morbidities and more often used cardio-protective medication on admission. Compared to patients with normal renal function, fewer with renal failure presented with chest pain (90% vs. 67%, P < 0.001), Killip I (89% vs. 58%, P < 0.001) and ST-elevation myocardial infarction (STEMI) (41% vs. 22%, P < 0.001). In a logistic regression model lower renal function was independently associated with a less frequent use of anticoagulant and revascularization in non-ST-elevation MI. The likelihood of receiving reperfusion therapy for STEMI was similar in patients with normal-to-moderate renal dysfunction, but decreased in severe renal dysfunction or renal failure. Reperfusion therapy shifted from primary percutaneous coronary intervention in 71% of patients with normal renal function to fibrinolysis in 58% of those with renal failure. Renal function was associated with a higher rate of complications and an exponential increase in in-hospital mortality from 2.5% to 24.2% across the renal function groups. CONCLUSION: Renal insufficiency influences the presentation and reduces the likelihood of receiving treatment according to current guidelines. Short-term prognosis remains poor.


Subject(s)
Myocardial Infarction/etiology , Renal Insufficiency, Chronic/complications , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Cardiotonic Agents/administration & dosage , Electrocardiography , Epidemiologic Methods , Female , Glomerular Filtration Rate , Hospitalization/statistics & numerical data , Humans , Kidney Function Tests/methods , Male , Middle Aged , Myocardial Infarction/mortality , Myocardial Infarction/therapy , Myocardial Revascularization/methods , Prognosis , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/physiopathology , Sweden/epidemiology
11.
Clin Nephrol ; 73(3): 221-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20178722

ABSTRACT

BACKGROUND: IgA nephropathy (IgAN), the most common chronic inflammatory kidney disease, implies a considerable risk of renal failure and premature cardiovascular disease. Metabolic activation of monocytes has been suggested to be an important link between chronic inflammation, oxidative stress and the development of atherosclerosis. Oxidative stress is also involved in the progression of kidney disease. In this study we investigated the degree of monocyte activation, measured by monocyte respiratory burst in patients with IgAN, since these patients represent a fairly homogenous group of patients with chronic kidney disease, and compared the results to those in healthy subjects. As anti- inflammatory effects have been ascribed to HMG-reductase inhibitors, we also examined whether treatment with atorvastatin influenced monocyte respiratory burst. METHODS: Monocyte respiratory burst, unstimulated and stimulated by fMLP and PMA, was measured by flow cytometry in 16 patients with biopsy proven IgAN before and after 1 month of treatment with 20 mg atorvastatin/ day. Baseline values were compared to measurements in healthy subjects. Blood and urine samples, before and after statin treatment, were also analyzed for ox-LDL, inflammatory markers (CRP, MCP-1, ICAM-1, TNFR II and NGAL/MMP-9) and renal functional parameters. RESULTS: At baseline, respiratory burst of PMA-stimulated monocytes was higher in patients with IgAN as compared to that in healthy subjects (p = 0.002). After atorvastatin treatment there was a significant reduction of unstimulated, fMLP- and PMA-stimulated monocyte respiratory burst compared to baseline values (p = 0.03, p = 0.003 and p = 0.002, respectively). For ox-LDL and inflammatory serum markers we observed no significant changes. CONCLUSION: Our study demonstrates a higher monocyte respiratory burst in patients with IgAN compared to in cells from healthy controls as well as a significant reduction of this parameter after short time and low dose atorvastatin treatment.


Subject(s)
Glomerulonephritis, IGA/metabolism , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Monocytes/metabolism , Pyrroles/therapeutic use , Respiratory Burst/drug effects , Adolescent , Adult , Aged , Atorvastatin , Biopsy , Biotransformation , Creatinine/blood , Creatinine/urine , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Follow-Up Studies , Glomerular Filtration Rate , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/pathology , Heptanoic Acids/pharmacokinetics , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Male , Middle Aged , Monocytes/drug effects , Oxidative Stress , Pyrroles/pharmacokinetics , Respiratory Burst/physiology , Treatment Outcome , Young Adult
12.
Scand J Immunol ; 70(4): 368-76, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19751271

ABSTRACT

The phenotypic alterations in monocytes induced by extravasation in vivo are still largely unknown. We addressed the question whether a general phenotype of extravasated monocytes exists and whether this phenotype differs between healthy individuals and statin treated patients with coronary artery disease (CAD). In vivo extravasated monocytes from CAD patients and healthy controls were collected by use of the skin blister method and compared with peripheral circulating monocytes by flow cytometry. The number of CD14(+)CD16(+) monocytes were significantly higher in the skin blister compared with peripheral circulation in both patients (P < 0.001) and controls (P = 0.005). In vivo extravasated monocytes had in comparison with peripheral monocytes a lower expression of CX(3)CR1, a higher expression of HLA-DR, CD86 and CD36 and a higher binding of acetylated low density lipoprotein (acLDL) (significant for all markers). Skin blister fluid from CAD patients, compared with healthy controls, induced a 20% increase in monocyte CD36 expression (P = 0.008) following 18 h of in vitro incubation. The results indicate that the integrated response to the in vivo extravasation process is similar in statin treated stable CAD patients and healthy controls, with respect to phenotypic alterations. Such differences in CAD patients may, however, occur as a response to the inflammatory milieu.


Subject(s)
B7-2 Antigen/metabolism , CD36 Antigens/metabolism , Cell Movement/immunology , HLA-DR Antigens/metabolism , Monocytes/metabolism , Receptors, Chemokine/metabolism , Receptors, IgG/metabolism , Aged , Blister/immunology , Blister/metabolism , Blister/pathology , CX3C Chemokine Receptor 1 , Cell Count , Coronary Artery Disease/drug therapy , Coronary Artery Disease/immunology , Coronary Artery Disease/metabolism , Female , GPI-Linked Proteins , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Lipoproteins, LDL/metabolism , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology
13.
Clin Exp Immunol ; 153(2): 196-204, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18460014

ABSTRACT

Coronary artery disease (CAD) is characterized by infiltration of monocyte derived cells in the intima of the vessel wall. We hypothesized that accumulation of these cells is caused partly by an altered monocyte transmigration process in CAD. To gain insight into this issue we applied the skin blister method that allows collection of in vivo transmigrated cells at sites of local inflammation. Nineteen patients with stable CAD and 19 matched controls were enrolled. Markers of inflammation and gradients of chemokines, as well as adhesion molecule expression and up-regulation capacity, were studied. The expression of inflammatory markers, such as C-reactive protein, interleukin (IL)-6, tumour necrosis factor-alpha and IL-10, was similar in patients and controls, indicating that patients were in a stable phase of the disease. Expression of adhesion molecules, CD11b and very late activation antigen-4, on peripheral monocytes did not differ between patients and controls. However, following in vivo transmigration, monocytes in patients with CAD had a significantly reduced expression and mobilization of CD11b. The effect on CD11b could not be reproduced by in vitro stimulation with blister fluid, representing a local inflammatory milieu, or in an in vitro system of transmigration. These findings point towards differences in monocyte CD11b expression and availability at an inflammatory site between patients with CAD and healthy controls.


Subject(s)
CD11b Antigen/immunology , Coronary Artery Disease/immunology , Leukocytes, Mononuclear/immunology , Aged , Atherosclerosis/immunology , Biomarkers/analysis , Blister/immunology , Case-Control Studies , Cell Movement , Coronary Artery Disease/drug therapy , Disease Progression , Female , Gene Expression , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Immunization , Integrin alpha4beta1/analysis , Interleukin-10/analysis , Interleukin-6/analysis , Male , Middle Aged , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/analysis
14.
Clin Exp Immunol ; 148(3): 573-82, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17386075

ABSTRACT

The transmigration of peripheral human monocytes to the interstitium is a fundamental step in the host-defence mechanism against infections. Little is known about the state of function of in vivo transmigrated interstitial monocytes prior to differentiation into macrophages and dendritic cells. We hypothesized that newly recruited interstitial monocytes have a preserved responsiveness against bacterial-related peptides, giving them a specific role in the immediate defence against invading pathogens. In order to test this hypothesis, we explored the responsiveness of in vivo transmigrated as well as peripheral monocytes, in terms of CD11b expression and H(2)O(2) production towards the bacterial-related peptide formylmethionylleucylphenylalanine (fMLP) by the use of a skin chamber technique. In addition, we analysed the concentration of interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor (TNF)-alpha in the skin blister exudates and in the circulation. We demonstrate that in vivo-transmigrated monocytes had a fivefold higher CD11b expression compared to monocytes obtained from the peripheral circulation. fMLP exposure induced a significantly higher CD11b expression on transmigrated cells compared to peripheral monocytes. In addition, newly recruited monocytes had a preserved H(2)O(2) production. The interstitial concentration of IL-8, MCP-1 and TNF-alpha was significantly higher in blister exudates compared to that in the peripheral circulation. Thus, in vivo transmigrated human monocytes preserve their capacity to respond towards bacterial peptides in terms of CD11b up-regulation and H(2)O(2) generation. These data strengthen a role for newly recruited interstitial human monocytes in the immediate defence against invading pathogens.


Subject(s)
Antigens, Bacterial/immunology , CD11b Antigen/metabolism , Hydrogen Peroxide/metabolism , Monocytes/immunology , Up-Regulation/immunology , Blister/immunology , Chemotactic Factors/metabolism , Chemotaxis, Leukocyte/immunology , Diffusion Chambers, Culture , Exudates and Transudates/immunology , Humans , Leukocyte Count , Middle Aged , N-Formylmethionine Leucyl-Phenylalanine/immunology , Respiratory Burst/immunology , Skin/immunology
15.
Kidney Int ; 71(6): 582-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17228360

ABSTRACT

The impact of high-flux hemodialysis on clinical outcomes remains controversial. We have previously shown that in vivo transmigrated leukocytes from patients with low-flux bioincompatible hemodialysis have an impaired capacity to upregulate CD11b at the site of interstitial inflammation. In the present study, we investigated the in vivo capacity of transmigrated monocytes and granulocytes to express CD11b at the site of interstitial inflammation in 10 patients on biocompatible high-flux hemodiafiltration or high-flux hemodialysis and 12 healthy subjects, and the in vitro response to a bacteria-related peptide (N-formyl-methionyl-leucyl-phenylalanine (fMLP)). Leukocyte formation of hydrogen peroxide (H(2)O(2)) and leukocyte apoptosis were also studied. In patients, both monocytes and granulocytes had a preserved capacity to express CD11b following in vivo transmigration to sites of interstitial inflammation, compared with cells from healthy subjects. Furthermore, monocytes and granulocytes from patients showed a preserved ability to respond to challenge with fMLP in the extravascular milieu. The intracellular killing capacity of leukocytes (H(2)O(2) production) in the interstitium was similar as of cells from healthy subjects both before and after stimulation with fMLP. Following maximal receptor independent stimulation (phorbol 12-myristate 13-acetate), leukocytes from patients showed lower H(2)O(2) production at the site of intense inflammation, compared with cells from healthy subjects. Finally, leukocyte apoptosis in interstitial inflammation was similar in patients and healthy subjects. We conclude that in vivo transmigrated leukocytes from patients on biocompatible high-flux hemodiafiltration or high-flux hemodialysis have a preserved capacity to express CD11b at the site of interstitial inflammation. This may have important biological implications.


Subject(s)
CD11b Antigen/metabolism , Hemodiafiltration/methods , Leukocytes/immunology , Nephritis, Interstitial/immunology , Nephritis, Interstitial/therapy , Adult , Aged , Apoptosis/physiology , CD11b Antigen/genetics , Case-Control Studies , Cell Movement/physiology , Female , Gene Expression Regulation/drug effects , Humans , Hydrogen Peroxide/metabolism , Leukocytes/metabolism , Leukocytes/pathology , Male , Middle Aged , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , Nephritis, Interstitial/pathology
16.
Scand J Immunol ; 62(6): 539-45, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16316421

ABSTRACT

In vitro studies have demonstrated that antineutrophil cytoplasmic antibodies (ANCA) have the capacity to activate neutrophils. Whether circulating neutrophils in patients with vasculitis are activated is under debate. Eight consecutive patients with antiproteinase 3 (PR3) positive acute vasculitis were included in this prospective study. Neutrophil expression of adhesion molecules, Fc-receptors and the ANCA-antigen PR3 was analysed and clinical characteristics were documented at inclusion and after 1, 3, 6 and 9 months in the same individuals. As additional markers of inflammation and endothelial activation interleukin-8 and soluble vascular cell adhesion molecule-1 in serum were analysed at the same time points. The expression of adhesion molecules on circulating neutrophils, CD62L and CD11b after in vitro N-formyl-methionyl-leucyl-phenylalanine stimulation was significantly decreased at diagnosis and after 1 month but returned to normal levels after 3-9 months. The neutrophil expression of Fc-receptor IIIb (CD 16) was decreased at diagnosis but normalized after 1-9 months. The main finding was an activated neutrophil adhesion phenotype at diagnosis and after 1 month, with normalized expression of adhesion molecules at 3-9 months. A pathological regulation of adhesion molecules may have implications on the endothelial damage seen in vasculitis.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Neutrophil Activation , Neutrophils/enzymology , Neutrophils/immunology , Serine Endopeptidases/immunology , Vasculitis/enzymology , Vasculitis/immunology , Antibodies, Antineutrophil Cytoplasmic/biosynthesis , Antibodies, Antineutrophil Cytoplasmic/physiology , Antigens, CD/blood , GPI-Linked Proteins , Humans , Interleukin-8/blood , L-Selectin/metabolism , Myeloblastin , Neutrophil Activation/immunology , Neutrophils/metabolism , Prospective Studies , Receptors, IgG/blood , Serine Endopeptidases/blood , Vascular Cell Adhesion Molecule-1/metabolism , Vasculitis/blood
17.
J Intern Med ; 255(1): 82-8, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14687242

ABSTRACT

OBJECTIVE: Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years (range: 23-30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. RESULTS: In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7-67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively, corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6. CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI.


Subject(s)
Body Mass Index , Infant, Small for Gestational Age/blood , Insulin Resistance/physiology , Insulin-Like Growth Factor Binding Protein 1/blood , Adult , Biomarkers/blood , Blood Glucose/analysis , Body Height/physiology , Female , Humans , Infant, Newborn , Infant, Premature/physiology , Insulin/blood , Insulin-Like Growth Factor I/analysis , Triglycerides/blood
18.
Scand J Rheumatol ; 33(6): 423-7, 2004.
Article in English | MEDLINE | ID: mdl-15794203

ABSTRACT

BACKGROUND: The monoclonal anti-B cell antibody rituximab (Rituxin, Mabthera) may be of benefit in antibody-driven diseases, including systemic lupus erythematosus (SLE) nephritis. PATIENTS AND TREATMENT: Two female patients with biopsy-confirmed severe and active SLE nephritis despite treatment with cyclophosphamide (CyX) were given four rituximab infusions plus two additional CyX infusions. RESULTS: Both patients tolerated the treatment well and SLE activity improved. On repeat kidney biopsy after the combined treatment, Patient 1 showed a profound reduction of nephritis activity, and she was maintained on low-dose prednisolone only. A repeat biopsy after 1 year confirmed the sustained reduction of lupus nephritis activity. In Patient 2, rebiopsy after combined treatment also showed a significant reduction in disease activity. CONCLUSION: These cases provide histopathological documentation of a significant treatment benefit from rituximab plus CyX in two patients refractory to CyX alone. This combination is being explored further as salvage therapy for such CyX-resistant patients.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Cyclophosphamide/therapeutic use , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Adult , Antibodies, Monoclonal, Murine-Derived , Biopsy, Needle , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Follow-Up Studies , Humans , Immunohistochemistry , Kidney Function Tests , Risk Assessment , Rituximab , Severity of Illness Index , Sweden , Treatment Outcome
19.
Scand J Clin Lab Invest ; 63(2): 127-33, 2003.
Article in English | MEDLINE | ID: mdl-12751694

ABSTRACT

Impaired haemostasis is common in patients with end-stage renal disease, and may cause either thrombotic or bleeding complications. The purpose of this study was to assess whether plasma markers of coagulation activation in patients undergoing chronic haemodialysis (HD) can identify high-risk individuals, and to test the relevancy of type of vascular access or dialysis filter. We measured plasma levels of prothrombin fragment 1+2, fibrin D-dimers and tissue factor in 82 HD patients before and after dialysis. Clinical endpoints during the year following blood sampling were thrombosis in blood access, changes in blood access, other thromboembolic events, bleeding complications, ischaemic vascular disease, or death. We found elevated baseline levels of all three parameters in HD patients, compared to normal reference ranges. Plasma levels of all parameters (particularly fibrin D-dimers) were significantly higher in patients with prosthetic grafts and central venous dialysis catheters than in patients with native vessels. Patients with AV-fistulas or grafts who had bleeding complications (n=7) had significantly higher plasma levels of fibrin D-dimer and prothrombin fragment 1+2. Bleeding complications also occurred more frequently among the patients with prosthetic grafts (3/18) or central venous dialysis catheters (3/11) compared with those with grafts from native vessels (1/53). Other than a bleeding tendency, our data do no show any correlation between coagulation parameters and other clinical complications during haemodialysis. In conclusion, we found elevated plasma levels of markers of coagulation activation among HD patients. High levels of D-dimers and prothrombin fragment 1+2 correlated to bleeding diathesis instead of thromboembolism, and this tendency was most pronounced in patients with prosthetic grafts.


Subject(s)
Hemorrhage/etiology , Kidney Failure, Chronic/complications , Renal Dialysis/adverse effects , Thrombosis/etiology , Aged , Catheters, Indwelling/adverse effects , Female , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/blood , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Peptide Fragments/blood , Prostheses and Implants/adverse effects , Prothrombin , Reference Values , Renal Dialysis/methods , Thromboplastin/analysis , Thrombosis/blood , Ultrafiltration
20.
Scand J Immunol ; 57(2): 179-84, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12588665

ABSTRACT

Monocyte in vitro activation by antimyeloperoxidase (anti-MPO)- and antiproteinase-3 (anti-PR3)-positive sera, corresponding immunoglobulin G (IgG) fractions and monoclonal antibodies against MPO and PR3 was evaluated. The expression of adhesion molecules, l-selectin (CD62L) and CR3 (CD11b), involved in leucocyte endothelial adhesion, and metabolic activity, measured as the production of hydrogen peroxide, were analysed. Decreased expression of CD62L was demonstrated in monocytes after incubation with antineutrophil cytoplasmic antibody (ANCA)-positive sera. This finding was not accompanied by changes in CD11b expression. Metabolic activity was increased in monocytes after incubation with ANCA-positive IgG fractions as well as after incubation with monoclonal anti-MPO and anti-PR3. These findings support the concept that the pathophysiological effect of ANCA is partly mediated through the action on crucial events in monocyte activation, such as CD62L downregulation and oxygen radical production.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/immunology , L-Selectin/blood , Monocytes/metabolism , Adolescent , Adult , Aged , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Biotransformation , CD11b Antigen/metabolism , Fluorescent Antibody Technique , Humans , Hydrogen Peroxide/metabolism , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , L-Selectin/immunology , Middle Aged , Monocytes/drug effects , Monocytes/immunology , Myeloblastin , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , Peroxidase/immunology , Peroxidase/metabolism , Serine Endopeptidases/immunology , Serine Endopeptidases/metabolism , Tetradecanoylphorbol Acetate/pharmacology
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