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1.
Nutr Metab Cardiovasc Dis ; 29(4): 343-350, 2019 04.
Article in English | MEDLINE | ID: mdl-30718141

ABSTRACT

BACKGROUND AND AIMS: Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients. METHODS AND RESULTS: Patients in Alpha Omega Cohort filled out a 203-item food-frequency questionnaire from which eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and LA intake were calculated. Circulating individual FA (% total FA) were assessed in cholesteryl esters (CE; n = 4066), phospholipids (PL; n = 838), and additionally in total plasma for DHA and LA (n = 739). Spearman correlation coefficients (rs) were calculated for dietary vs. circulating FA. Circulating FA were also compared across dietary FA quintiles, overall and in subgroups by sex, obesity, diabetes, statin use, and high alcohol intake. Patients were on average 69 years old and 79% was male. Moderate correlations between dietary and circulating levels were observed for EPA (rs∼0.4 in CE and PL) and DHA (rs ∼0.5 in CE and PL, ∼0.4 in total plasma), but not for ALA (rs ∼0.0). Weak correlations were observed for LA (rs 0.1 to 0.2). Plasma LA was significantly lower in statin users and in patients with a high alcohol intake. CONCLUSIONS: In post-MI patients, dietary EPA and DHA were well reflected in circulating levels. This was not the case for LA, which may partly be influenced by alcohol use and statins.


Subject(s)
Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Feeding Behavior , Linoleic Acid/blood , Myocardial Infarction/blood , Aged , Aged, 80 and over , Alcohol Drinking/blood , Biomarkers/blood , Cross-Sectional Studies , Diet Records , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/drug therapy , Netherlands , Prospective Studies
2.
Eur J Clin Nutr ; 71(2): 245-251, 2017 02.
Article in English | MEDLINE | ID: mdl-27827396

ABSTRACT

OBJECTIVE: The aim of this study was to examine the relations between intakes of total, saturated, mono-unsaturated, poly-unsaturated and trans fatty acids (SFA, MUFA, PUFA and TFA), and their dietary sources (dairy, meat and plant) with markers of type 2 diabetes risk. SUBJECTS/METHODS: This was a cross-sectional analysis of baseline data of 5675 non-diabetic, middle-aged participants of the Netherlands Epidemiology of Obesity (NEO) study. Associations between habitual dietary intake and fasting and postprandial blood glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of ß-cell function (HOMA-B) and Disposition Index were assessed through multivariable linear regression models with adjustments for demographic, lifestyle and dietary factors. RESULTS: Mean (s.d.) intakes in percent of energy (En%) were 34.4 (5.8) for total fatty acids, 12.4 (2.9) for SFA, 12.2 (2.4) for MUFA, 6.9 (1.9) for PUFA and 0.6 (0.2) for TFA. As compared with carbohydrates, only SFA was weakly inversely associated with fasting insulin, HOMA-IR and HOMA-B. When stratified by dietary source, all fatty acids from meat were positively associated with fasting insulin - total fatty acidsmeat (per 5 En%: 10.0%; 95% confidence interval: 4.0, 16.3), SFAmeat (per 1 En%: 3.7%; 0.4, 7.2), MUFAmeat (per 1 En%: 5.0%; 2.0, 8.1), PUFAmeat (per 1 En%: 17.3%; 6.0, 29.7) and TFAmeat (per 0.1 En%: 10.5%; 3.2, 18.3). Similarly, all fatty acids from meat were positively associated with HOMA-IR and HOMA-B and inversely with Disposition Index. CONCLUSIONS: Our study suggests that the relations between fatty acid intakes and markers of type 2 diabetes risk may depend on the dietary sources of the fatty acids. More epidemiological studies on diet and cardiometabolic disease are needed, addressing possible interactions between nutrients and their dietary sources.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diet/methods , Dietary Fats/blood , Fatty Acids/blood , Postprandial Period/physiology , Biomarkers/blood , Blood Glucose/analysis , Cross-Sectional Studies , Dairy Products/analysis , Diabetes Mellitus, Type 2/etiology , Dietary Fats/administration & dosage , Dietary Fats/analysis , Energy Intake/physiology , Fasting/blood , Fatty Acids/administration & dosage , Fatty Acids/analysis , Female , Humans , Insulin/blood , Linear Models , Male , Meat/analysis , Middle Aged , Netherlands , Plants, Edible/chemistry , Risk Factors
3.
Int J Obes (Lond) ; 38(6): 794-800, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24030518

ABSTRACT

BACKGROUND: Viscous or gel-forming dietary fibers can increase satiety by a more firm texture and increased eating time. Effects of viscous or gel-forming fibers on satiety by post-ingestive mechanisms such as gastric emptying, hormonal signals, nutrient absorption or fermentation are unclear. Moreover, it is unclear whether the effects persist after repeated exposure. OBJECTIVE: To investigate satiety and energy intake after single and repeated exposure to gelled fiber by post-ingestive mechanisms. DESIGN: In a two-arm crossover design, 32 subjects (24 female subjects, 21±2 y, BMI 21.8±1.9 kg m(-2)) consumed test foods once daily for 15 consecutive days, with 2 weeks of washout. Test foods were isocaloric (0.5 MJ, 200 g) with either 10 g gel-forming pectin or 3 g gelatin and 2 g starch, matched for texture and eating time. Hourly satiety ratings, ad libitum energy intake and body weight were measured on days 1 (single exposure) and 15 (repeated exposure). In addition, hourly breath hydrogen, fasting glucose, insulin, leptin and short-chain fatty acids were measured. RESULTS: Subjects rated hunger, desire to eat and prospective intake about 2% lower (P<0.015) and fullness higher (+1.4%; P=0.041) when they received pectin compared with control. This difference was similar after single and repeated exposure (P>0.64). After receiving pectin, energy intake was lower (-5.6%, P=0.012) and breath hydrogen was elevated (+12.6%, P=0.008) after single exposure, but not after repeated exposure. Fasting glucose concentrations were higher both after single and repeated exposure to pectin (+2.1%, P=0.019). Body weight and concentrations of insulin, leptin and short-chain fatty acids did not change during the study. CONCLUSIONS: Gelled pectin can increase satiety and reduce energy intake by post-ingestive mechanisms. Although the effects were small, the effects on satiety were consistent over time, whereas the effects on energy intake reduction were not.


Subject(s)
Dietary Fiber/administration & dosage , Energy Intake/physiology , Galactans/administration & dosage , Gastric Emptying/physiology , Mannans/administration & dosage , Pectins/administration & dosage , Plant Gums/administration & dosage , Satiation/physiology , Administration, Oral , Adult , Blood Glucose , Cross-Over Studies , Double-Blind Method , Eating , Fasting , Female , Humans , Hunger/physiology , Insulin , Leptin , Male
4.
Eur J Clin Nutr ; 67(5): 541-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23531781

ABSTRACT

This review asks the question if further research on trans fatty acids and cardiovascular health is needed. We therefore review the evidence from human studies on trans fatty acids and cardiovascular health, and provide a quantitative review of effects of trans fatty acid intake on lipoproteins. The results show that the effect of industrially produced trans fatty acids on heart health seen in observational studies is larger than predicted from changes in lipoprotein concentrations. There is debate on the effect of ruminant trans fatty acids and cardiovascular disease. Of special interest is conjugated linoleic acid (CLA), which is produced industrially for sale as supplements. Observational studies do not show higher risks of cardiovascular disease with higher intakes of ruminant trans fatty acids. However, CLA, industrial and ruminant trans fatty acids all raise plasma low-density lipoprotein and the total to high-density lipoprotein ratio. Gram for gram, all trans fatty acids have largely the same effect on blood lipoproteins. In conclusion, the detrimental effects of industrial trans fatty acids on heart health are beyond dispute. The exact size of effect will remain hard to determine. Further research is warranted on the effects of ruminant trans fatty acids and CLA on cardiovascular disease and its risk factors.


Subject(s)
Cardiovascular Diseases/etiology , Heart/drug effects , Linoleic Acid/adverse effects , Linoleic Acids, Conjugated/adverse effects , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Trans Fatty Acids/adverse effects , Animals , Cardiovascular Diseases/blood , Dietary Supplements , Humans
5.
J Hum Hypertens ; 26(2): 127-32, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21270839

ABSTRACT

Cis-9, trans-11 conjugated linoleic acid (CLA) is a natural trans fatty acid that is largely restricted to ruminant fats and consumed in foods and supplements. Its role in blood pressure (BP) regulation is still unclear. We examined the effect of cis-9, trans-11 CLA on BP compared with oleic acid. A total of 61 healthy volunteers were sequentially fed each of 3 diets for 3 weeks, in random order, for a total of 9 weeks. The diets were identical except for 7% of energy (18.9 g in a diet of 10 MJ day(-1)) that was provided either by oleic acid, by industrial trans fatty acids or by cis-9, trans-11 CLA. We measured BP on two separate days at the end of each intervention period. At baseline, mean BP was 113.8±14.4 mm Hg systolic and 66.3±9.6 mm Hg diastolic. The effect of the CLA diet compared with the oleic acid diet was 0.11 mm Hg (95% confidence interval: -1.27, 1.49) systolic and -0.45 mm Hg (-1.63, 0.73) diastolic. After the industrial trans fatty acid diet, the effect was 1.13 mm Hg (-0.25, 2.51) systolic and -0.44 mm Hg (-1.62, 0.73) diastolic compared with the oleic acid diet. Our study suggests that short-term high intakes of cis-9,trans-11 CLA do not affect BP in healthy volunteers.


Subject(s)
Blood Pressure , Dairy Products , Dietary Fats/administration & dosage , Dietary Supplements , Food, Fortified , Linoleic Acids, Conjugated/administration & dosage , Meat , Oleic Acid/administration & dosage , Adolescent , Adult , Cross-Over Studies , Female , Humans , Male , Middle Aged , Netherlands , Time Factors , Treatment Outcome , Young Adult
6.
Obes Rev ; 12(9): 724-39, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21676152

ABSTRACT

Dietary fibres are believed to reduce subjective appetite, energy intake and body weight. However, different types of dietary fibre may affect these outcomes differently. The aim of this review was to systematically investigate the available literature on the relationship between dietary fibre types, appetite, acute and long-term energy intake, and body weight. Fibres were grouped according to chemical structure and physicochemical properties (viscosity, solubility and fermentability). Effect rates were calculated as the proportion of all fibre-control comparisons that reduced appetite (n = 58 comparisons), acute energy intake (n = 26), long-term energy intake (n = 38) or body weight (n = 66). For appetite, acute energy intake, long-term energy intake and body weight, there were clear differences in effect rates depending on chemical structure. Interestingly, fibres characterized as being more viscous (e.g. pectins, ß-glucans and guar gum) reduced appetite more often than those less viscous fibres (59% vs. 14%), which also applied to acute energy intake (69% vs. 30%). Overall, effects on energy intake and body weight were relatively small, and distinct dose-response relationships were not observed. Short- and long-term effects of dietary fibres appear to differ and multiple mechanisms relating to their different physicochemical properties seem to interplay. This warrants further exploration.


Subject(s)
Appetite/drug effects , Body Weight/drug effects , Dietary Fiber/administration & dosage , Energy Intake/drug effects , Dietary Fiber/classification , Dietary Fiber/metabolism , Fermentation , Humans , Obesity/prevention & control , Randomized Controlled Trials as Topic , Solubility , Viscosity
7.
Tijdschr Psychiatr ; 52(5): 349-52, 2010.
Article in Dutch | MEDLINE | ID: mdl-20458682

ABSTRACT

Differentiating panic disorder form epilepsy can be a difficult task. In this case study the task was made more complicated because the patient was being treated with the selective serotonin reuptake inhibitor (SSRI) citalopram which evoked a partial response, thereby delaying the diagnosis of epilepsy. Research results demonstrate that ssris can have not only an antidepressive and calming effect, they can also have an anticonvulsant effect. However, there are also signs that, as this case illustrates, in the long term the anticonvulsant effect can actually convert to proconvulsant effect.


Subject(s)
Citalopram/adverse effects , Epilepsy/diagnosis , Panic Disorder/diagnosis , Selective Serotonin Reuptake Inhibitors/adverse effects , Adult , Citalopram/therapeutic use , Diagnosis, Differential , Humans , Male , Panic Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use
8.
Food Chem Toxicol ; 48(2): 587-90, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19932729

ABSTRACT

Conjugated linoleic acid (CLA) is consumed widely as a supplement. It causes hepatomegaly in animals, but toxicological data in humans are limited. We therefore studied the effect of a high daily intake of CLA on liver and kidney function in healthy subjects. Twenty subjects received 14.6 g cis-9,trans-11 CLA and 4.7 g trans-10,cis-12 CLA isomers a day for 3 weeks. Liver and kidney function was measured at 0, 3, 7, 10, 16, and 21 days. Mean values of all tests remained within normal limits. Lactate dehydrogenase (mean+/-SD) increased from 290.9+/-43.6 to 322.5+/-60.7 U/L (p=0.04) on day 21. One subject exceeded the upper limit of normal of 450 U/L on day 21, to 472 U/L and another showed an isolated elevation to 555 U/L on day 7. Gamma-glutamyltranspeptidase increased from 12.1+/-5.9 to 13.5+/-6.2U/L (p=0.002). No one exceeded the upper limit of 50 U/L for men and 40 U/L for women. A daily intake of 19.3 g CLA for 3 weeks does not produce clinically relevant effects on markers of liver and kidney function in healthy volunteers.


Subject(s)
Kidney/drug effects , Linoleic Acids, Conjugated/administration & dosage , Liver/drug effects , Adolescent , Adult , Clinical Chemistry Tests , Dietary Supplements , Female , Humans , Kidney/physiology , Kidney Function Tests , L-Lactate Dehydrogenase/blood , Liver/physiology , Liver Function Tests , Male , Middle Aged , Reference Values , Young Adult , gamma-Glutamyltransferase/blood
9.
Br J Cancer ; 100(2): 334-43, 2009 Jan 27.
Article in English | MEDLINE | ID: mdl-19142186

ABSTRACT

Heat shock protein 90 (Hsp90) has been demonstrated to protect oncogenic variants of signalling molecules from degradation and may consequently serve as a therapeutic target for the treatment of oesophageal cancer for which adequate therapy is often lacking. We studied the expression of Hsp90 in tumour tissues of human oesophageal cancer and the impact of Hsp90 inhibition on oesophageal cancer cell lines using the drug 17-allylamino-17-demethoxygeldanamycin (17-AAG). Quantitative immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues from patients with oesophageal cancer. In squamous cell carcinoma, a marked upregulation of Hsp90 could be noted in dysplastic epithelium and invasive cancer compared with normal epithelium. In adenocarcinoma, Hsp90 was expressed in neoplastic epithelium and also in normal non-neoplastic glands weakly. The inhibition of Hsp90 using 17-AAG led to a significant decrease in cell proliferation and viability in human oesophageal cancer cell lines. Using a clonogenic cell survival assay, Hsp90 inhibition significantly sensitised the cells for gamma-photon irradiation. Heat shock protein 90 was found to be critical for proper signalling induced by both epidermal growth factor and insulin-like growth factor-1, in which the inhibition of signalling by 17-AAG correlated with the observed reduction in cell proliferation and viability. These results showed that Hsp90 was selectively expressed in oesophageal cancer tissue compared with the corresponding normal tissue, and the inhibition of Hsp90 resulted in decreased proliferation and viability as well as radiosensitisation of oesophageal cancer cells. Heat shock protein 90 represents a potential therapeutic target in the treatment of patients with oesophageal cancer, alone or in combination with radiotherapy.


Subject(s)
Benzoquinones/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , HSP90 Heat-Shock Proteins/metabolism , Lactams, Macrocyclic/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Apoptosis/drug effects , Apoptosis/radiation effects , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Female , Gamma Rays , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Humans , Immunoenzyme Techniques , Immunoprecipitation , Male , Prognosis , Signal Transduction/drug effects , Survival Rate , Tumor Cells, Cultured , Tumor Stem Cell Assay
11.
Dis Esophagus ; 19(4): 224-31, 2006.
Article in English | MEDLINE | ID: mdl-16866851

ABSTRACT

The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.


Subject(s)
Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Neoplasms, Squamous Cell/metabolism , Neoplasms, Squamous Cell/mortality , Receptor, ErbB-2/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Aged , Esophageal Neoplasms/genetics , Esophageal Neoplasms/therapy , Female , Gene Expression , Genes, erbB-2 , Humans , Immunohistochemistry , In Situ Hybridization , Male , Neoplasm Metastasis , Neoplasms, Squamous Cell/genetics , Neoplasms, Squamous Cell/therapy , Radiation Tolerance , Retrospective Studies , Survival Analysis
12.
Br J Cancer ; 94(10): 1478-84, 2006 May 22.
Article in English | MEDLINE | ID: mdl-16641897

ABSTRACT

The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-gamma secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-gamma upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Colonic Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Aged , Aged, 80 and over , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Female , Flow Cytometry , Humans , Immunotherapy , Lymph Nodes/immunology , Lymphatic Metastasis , Lymphocyte Activation , Male , Middle Aged , Neoplasm Staging , Sentinel Lymph Node Biopsy , Survival Rate
13.
Ann Rheum Dis ; 65(6): 804-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16219703

ABSTRACT

OBJECTIVE: To compare the contribution of changes on magnetic resonance imaging (MRI) and conventional radiography (CR) in the sacroiliac joints of patients with recent onset inflammatory back pain (IBP) in making an early diagnosis of spondyloarthritides. METHODS: The study involved 68 patients with IBP (38% male; mean (SD) age, 34.9 (10.3) years) with symptom duration less than two years. Coronal MRI of the sacroiliac joints was scored for inflammation and structural changes, and pelvic radiographs were scored by the modified New York (mNY) grading. Agreement between MRI and CR was analysed by cross tabulation per sacroiliac joint and per patient. RESULTS: A structural change was detected in 20 sacroiliac joints by MRI and in 37 by CR. Inflammation was detected in 36 sacroiliac joints by MRI, and 22 of these showed radiographic sacroiliitis. Fourteen patients fulfilled the mNY criteria based on CR. Classification according to the modified New York criteria would be justified for eight patients if it was based on MRI for structural changes only, for 14 if it was based on structural changes on CR, for 14 (partly) different patients if it was based on inflammation on MRI only, for 16 if it was based on inflammation and structural changes on MRI, for 19 if it was based on inflammation on CR combined with MRI, and for (the same) 19 if it was based on inflammation and structural damage on CR combined with MRI. CONCLUSIONS: CR can detect structural changes in SI joints with higher sensitivity than MRI. However, inflammation on MRI can be found in a substantial proportion of patients with IBP but normal radiographs. Assessment of structural changes by CR followed by assessment of inflammation on MRI in patients with negative findings gives the highest returns for detecting involvement of the SI joints by imaging in patients with recent onset IBP.


Subject(s)
Arthritis/pathology , Back Pain/etiology , Magnetic Resonance Imaging , Sacroiliac Joint/pathology , Adult , Arthritis/diagnostic imaging , Arthritis/immunology , Back Pain/immunology , Female , History, 16th Century , Humans , Male , Observer Variation , Predictive Value of Tests , Radiography , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/immunology , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/immunology , Spondylitis, Ankylosing/pathology
14.
Ann Rheum Dis ; 64(7): 988-94, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15958757

ABSTRACT

OBJECTIVE: To demonstrate the association between various measures of spinal mobility and radiographic damage of the spine in individual patients with ankylosing spondylitis, and to determine whether the assessment of spinal mobility can be a proxy for the assessment of radiographic damage. METHODS: Radiographic damage was assessed by the mSASSS. Cumulative probability plots combined the radiographic damage score of an individual patient with the corresponding score for nine spinal mobility measures. Receiver operating characteristic analysis was performed to determine the cut off level of every spinal mobility measure that discriminates best between the presence and absence of radiographic damage. Three arbitrary cut off levels for radiographic damage were investigated. Likelihood ratios were calculated to explore further the diagnostic properties of the spinal mobility measures. RESULTS: Cumulative probability plots showed an association between spinal mobility measures and radiographic damage for the individual patient. Irrespective of the chosen cut off level for radiographic progression, lateral spinal flexion and BASMI discriminated best between patients with and those without structural damage. Even the best discriminatory spinal mobility assessments misclassified a considerable proportion of patients (up to 20%). Intermalleolar distance performed worst (up to 30% misclassifications). Lateral spinal flexion best predicted the absence of radiographic damage, and a modified Schober test best predicted the presence of radiographic damage. CONCLUSION: This study unequivocally demonstrated a relationship between spinal mobility and radiographic damage. However, spinal mobility cannot be used as a proxy for radiographic evaluation in an individual patient.


Subject(s)
Spine/diagnostic imaging , Spondylitis, Ankylosing/diagnostic imaging , Adult , Cohort Studies , Female , Humans , Male , Movement , Probability , ROC Curve , Radiography , Spine/physiopathology , Spondylitis, Ankylosing/physiopathology
15.
Gut ; 54(12): 1714-20, 2005 Dec.
Article in English | MEDLINE | ID: mdl-15886302

ABSTRACT

AIM: The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (UC). METHODS: Biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control subjects. Cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. The use of scatter plot-gating and specific antibodies was established in a flow cytometry assay. RESULTS: Eosinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. Neutrophils were increased in number and activity during active but not inactive UC. In patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum. CONCLUSION: With this method, we confirm that neutrophils participate in the inflammatory process during active UC, and that they express a resting phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. Nevertheless, our new finding of high eosinophil activation during inactive UC suggests that eosinophils play a role in repair of injured epithelium.


Subject(s)
Colitis, Ulcerative/pathology , Eosinophils/physiology , Adult , Aged , Antigens, CD/metabolism , Biopsy , Cell Adhesion Molecules/metabolism , Cells, Cultured , Colitis, Ulcerative/drug therapy , Eosinophils/pathology , Female , Flow Cytometry/methods , GPI-Linked Proteins , Humans , Immunoenzyme Techniques , Intestine, Large/pathology , Male , Middle Aged , Neutrophil Activation , Remission Induction , Severity of Illness Index
16.
MAGMA ; 18(2): 59-62, 2005 May.
Article in English | MEDLINE | ID: mdl-15711849

ABSTRACT

A chemical-shift imaging technique was used for the study of small subcutaneous lesions. This study concerns micro-imaging of two females suffering from a tenosynovial giant cell tumor and an epidermal cyst. High-resolution water, fat and chemical-shift artifact-free images were obtained on a whole-body MR unit (1.5 T) equipped with a 23-mm microscopy surface coil and standard gradients (23 mT/m). A significant improvement in signal-to-noise ratio was achieved by reducing the receiver bandwidth to values below +/-10 kHz. The image data sets were acquired with resolution 0.1 x 0.13 mm in the plane, slice thickness 0.5 mm and with acquisition time less than 3 min. Spatial resolution, fat suppression, image texture and edge delineation were improved on spectroscopic images compared with those on conventional MR images.


Subject(s)
Algorithms , Epidermal Cyst/pathology , Giant Cell Tumors/pathology , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Skin Diseases/pathology , Soft Tissue Neoplasms/pathology , Adult , Female , Humans , Middle Aged , Synovial Membrane/pathology , Tendons/pathology
17.
Gut ; 53(12): 1806-12, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15542519

ABSTRACT

BACKGROUND AND AIMS: There is a clear need for a rapid, simple, safe, and sensitive method of determining the type and intensity of inflammation in the gut mucosa in clinical practice. In this study, we have evaluated the potential of a new method, the mucosal patch technique, in patients with and without apparent gut inflammation, as assessed by conventional diagnostic procedures. SUBJECTS AND METHODS: The technique tested is based on the idea that inflammatory mediators released from the rectal mucosa can be absorbed by and then extracted from cellulose patches brought into contact with the mucosa by use of an instrument with an inflatable balloon. Measurements were performed in healthy controls (n = 16) and in patients with active (n = 19) and inactive ulcerative colitis (UC, n = 8), collagen colitis (CC, n = 12), coeliac disease (n = 13), and irritable bowel syndrome (IBS, n = 13). RESULTS: Inflammatory mediators from neutrophils (myeloperoxidase (MPO)) and eosinophils (eosinophil cationic protein (ECP)) were increased on average 300- and 10-fold, respectively, in patients with active UC compared with healthy controls and were correlated with the endoscopic score. Patients with inactive UC, CC, coeliac disease, and IBS exhibited no endoscopic signs of inflammation. These patient groups had significantly lower levels of MPO and ECP than the active UC group but showed on average a four- to sevenfold increase in MPO compared with healthy controls. CONCLUSION: The mucosal patch technique was well tolerated by patients and easily applied by the investigator. Pronounced neutrophil and eosinophil involvement in UC was demonstrated. With the high sensitivity of the technique, low degree mucosal neutrophil activation could also be quantified in patients with CC and UC in clinical remission. The finding of increased neutrophil involvement in patients with IBS contributes to the pathophysiological ideas of this disease.


Subject(s)
Eosinophils/pathology , Inflammatory Bowel Diseases/diagnosis , Intestinal Mucosa/pathology , Irritable Bowel Syndrome/diagnosis , Neutrophil Activation , Adult , Biomarkers/analysis , Eosinophil Cationic Protein/analysis , Female , Humans , Inflammation Mediators/metabolism , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Irritable Bowel Syndrome/metabolism , Irritable Bowel Syndrome/pathology , Male , Middle Aged , Patient Compliance , Peroxidase/analysis , Rectum/metabolism , Specimen Handling/instrumentation , Specimen Handling/methods
18.
Ann Rheum Dis ; 63(12): 1601-4, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15297280

ABSTRACT

OBJECTIVES: To describe the influence of the reading order (chronological v paired) on radiographic scoring results in ankylosing spondylitis. To investigate whether this method is sufficiently sensitive to change because paired reading is requested for establishing drug efficacy in clinical trials. METHODS: Films obtained from 166 patients (at baseline, 1 year, and 2 years) were scored by one observer, using the modified Stoke Ankylosing Spondylitis Spinal Score. Films were first scored chronologically, and were scored paired 6 months later. RESULTS: Chronological reading showed significantly more progression than paired reading both at 1 year (mean (SD) progression 1.3 (2.6) v 0.5 (2.4) units) and at 2 years (2.1 (3.9) v 1.0 (2.9) units); between-method difference: p<0.001 at 1 year, and p<0.001 at 2 years. After 1 year, progression (>0 units) was found in 35/166 (21%) patients after paired reading and in 55/166 (33%) after chronological reading. After 2 years, these figures were 50/166 (30%) and 68/166 (41%), respectively. Sample size calculations showed that 94 patients in each treatment arm are required in a randomised clinical trial (RCT) to provide sufficient statistical power to detect a difference in 2 year progression if films are scored paired. CONCLUSION: Reading with chronological time order is more sensitive to change than reading with paired time order, but paired reading is sufficiently sensitive to pick up change with a follow up of 2 years, resulting in an acceptable sample size for RCTs.


Subject(s)
Randomized Controlled Trials as Topic/methods , Spondylitis, Ankylosing/diagnostic imaging , Adult , Chronology as Topic , Disease Progression , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Radiography , Reproducibility of Results , Research Design , Sensitivity and Specificity , Severity of Illness Index , Spondylitis, Ankylosing/drug therapy , Time Factors , Treatment Outcome
19.
Ann Rheum Dis ; 63(11): 1368-71, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15231507

ABSTRACT

To increase change between groups, randomised clinical trials (RCT) often include patients with high risk for a particular outcome, by inclusion criteria that select predictors for that outcome. This increases the statistical power, and fewer patients are required for that RCT. The way in which patient selection influences the power, and thus sample size required, depends on how an intervention reduces the individual risk: by an absolute or relative risk reduction model.


Subject(s)
Patient Selection , Randomized Controlled Trials as Topic , Rheumatology/methods , Humans , Sample Size
20.
Acta Radiol ; 44(5): 472-84, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14510752

ABSTRACT

PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on normal red bone marrow MR imaging in breast cancer patients with focal bone metastases. MATERIAL AND METHODS: Fifteen breast cancer patients who were examined before and after chemotherapy with T1-weighted-SE and long echo-time inversion-recovery turbo-spin-echo (long TE IR-TSE) sequences in the thoracolumbar spine and pelvis were retrospectively studied. Nine of them received G-CSF therapy after the administration of each chemotherapy course. Of these 9 patients, the MR follow-ups were performed during G-CSF in 4 patients and after G-CSF therapy in 5 patients. Six patients did not receive G-CSF. Signal intensity (SI) changes in normal bone marrow were evaluated visually in all patients and quantitatively in 13 patients. RESULTS: In all 4 patients investigated during G-CSF therapy a diffuse, homogeneous SI increase on long TE IR-TSE was observed visually and quantitatively in initially normal bone marrow. This change obscured some focal lesions in 2 patients. No such SI change was visible after G-CSF therapy (p = 0.008) or in patients not receiving G-CSF. On T1-weighted images an SI decrease was found both during and after G-CSF therapy, but an increase occurred in patients not receiving G-CSF. CONCLUSION: G-CSF-supported chemotherapy can induce diffuse SI changes in normal red bone marrow on MR imaging. On long TE IR-TSE, the changes are visible during G-CSF treatment and can lead to misinterpretations in the response evaluation of bone metastases to therapy.


Subject(s)
Bone Marrow/pathology , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Granulocyte Colony-Stimulating Factor/therapeutic use , Magnetic Resonance Imaging , Adult , Aged , Drug Therapy, Combination , Humans , Middle Aged , Retrospective Studies
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