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ABSTRACT: Early diagnosis and dietary treatment with a gluten-free diet might slow down the progression of associated autoimmune diseases in celiac disease, but the data are contradictory. We investigated the course of autoimmune thyroid diseases in newly diagnosed celiac disease patients before and after gluten-free dietary treatment.
Twenty-seven consecutive adults with newly diagnosed celiac disease were investigated at the time of diagnosis and after 1 year on gluten-free diet. Earlier diagnosed and subclinical autoimmune thyroid diseases were recorded and examined. Thyroid gland volume and echogenicity were measured by ultrasound. Autoantibodies against celiac disease and thyroiditis, and thyroid function tests were determined. For comparison, 27 non-celiac controls on normal gluten-containing diet were examined.
At the time of diagnosis, the celiac disease patients had more manifest (n = 7) or subclinical (n = 3) thyroid diseases than the controls (10/27 vs. 3/27, p = 0.055). During the follow-up, the thyroid volume decreased significantly in the patients with celiac disease compared with the controls, indicating the progression of thyroid gland atrophy despite the gluten-free diet.
Celiac patients had an increased risk of thyroid autoimmune disorders. A gluten-free diet seemed not to prevent the progression of autoimmune process during a follow-up of 1 year.
Scandinavian journal of gastroenterology 11/2011; 47(1):43-8. · 2.08 Impact Factor
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New England Journal of Medicine 10/2008; 359(13):1408-9; author reply 1409. · 53.30 Impact Factor
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ABSTRACT: Previous studies suggest that hyperthyroid patients remain at increased risk of cardiovascular morbidity after restoring euthyroidism. The aim of this study was to compare the rate and causes of hospitalization of hyperthyroid patients treated with radioactive iodine (RAI) with those of an age- and gender-matched reference population in a long-term follow-up study.
A population-based cohort study with a median follow-up time of 9 years was conducted among 2611 hyperthyroid patients treated with RAI between 1969 and 2002 in Tampere University Hospital, and among 2611 reference subjects. Information on hospitalizations was obtained from the nationwide Hospital Discharge Registry. New events were analysed as the main outcome, including only the first hospitalization due to a given indication.
The rate of hospitalization due to cardiovascular disease (CVD) was higher among patients with hyperthyroidism than among the control population [637.1 vs. 476.4 per 10 000 person-years, rate ratio (RR) 1.12, 95% confidence interval (CI) 1.03-1.21]. The risk remained elevated up to 35 years after the RAI treatment. Hospitalizations due to atrial fibrillation (RR 1.35), cerebrovascular disease (RR 1.31), diseases of other arteries and veins (RR 1.22), hypertension (RR 1.20) and heart failure (RR 1.48) were more frequent in the patients than controls, while no such difference was found for coronary artery disease. Hospitalizations due to cancer, infectious and gastrointestinal diseases, and fractures were also more common in patients than in controls.
Hyperthyroidism increases hospitalizations due to CVDs. The excess risk is sustained decades after treatment. Patients treated for hyperthyroidism constitute a high-risk group for CVD and may benefit from preventive interventions.
Clinical Endocrinology 04/2008; 68(3):450-7. · 3.17 Impact Factor
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ABSTRACT: Patients treated with radioiodine (RAI) for hyperthyroidism have been reported to be at increased risk for death. It is not clear whether the increased mortality is due to hyperthyroidism itself or the effect of RAI.
Our objective was to compare the mortality of hyperthyroid patients treated with RAI with that of an age- and gender-matched reference population.
We conducted a population-based cohort study.
A total of 2793 patients who received RAI treatment for hyperthyroidism in Tampere University Hospital between 1965 and 2002, and 2793 reference subjects were followed for a median of 9 yr.
Record linkage with Statistics Finland identified all-cause mortality of 453 vs. 406 per 10,000 person-years in the patients and controls [rate ratio (RR) 1.12; 95% confidence interval 1.03-1.20]. Cerebrovascular diseases accounted for most of the increased mortality among patients (RR 1.40), and mortality from cancer increased (RR 1.29) as well. The risk of death increased in patients older than 60 yr at treatment. Mortality increased with the dose of RAI and was elevated in patients with nodular thyroid disease, but not in those with Graves' disease. Previous treatment with partial thyroidectomy decreased, whereas antithyroid medication did not affect mortality. In Cox regression analysis, RAI-treated hyperthyroidism (RR 1.56) and age (RR 1.10/1 yr) increased, and the development of hypothyroidism (RR 0.52) reduced mortality significantly.
Hyperthyroidism per se probably accounts for the increased cerebrovascular mortality after RAI treatment. Our results of increased cerebrovascular and cancer mortality emphasize the need for long-term vigilance concerning patients treated with RAI.
Journal of Clinical Endocrinology & Metabolism 07/2007; 92(6):2190-6. · 6.50 Impact Factor
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ABSTRACT: Concerns remain about risk of cancer after radioactive iodine (RAI) treatment for hyperthyroidism, especially in organs that concentrate iodine. The objective was to assess the long-term cancer risk from RAI treatment for hyperthyroidism.
A total of 2793 hyperthyroid patients treated with RAI at Tampere University Hospital between 1965 and 2002, and 2793 age- and sex-matched reference subjects were followed for an average of 10 years through the Finnish Cancer Registry.
Cancer incidence among hyperthyroid patients treated with RAI was higher than in the population-based control group (118.9 vs 94.9 per 10,000 person-years, rate ratio [RR], 1.25; 95% confidence interval [CI]: 1.08-1.46). Furthermore, incidence of stomach (RR, 1.75, 95% CI: 1.00-3.14), kidney (RR, 2.32; 95% CI: 1.06-5.09), and breast (RR, 1.53; 95% CI: 1.07-2.19) cancer was increased among RAI-treated patients. The relative risk of cancer increased with higher RAI dose administered. The increase in cancer incidence was statistically significant in patients treated at the age of 50-59 (RR, 1.44; 95% CI: 1.05-1.97) or older than 70 years (RR, 1.39; 95% CI: 1.05-1.82). There was a 5-year latent period after the RAI treatment before the cancer incidence began to differ between the RAI-treated hyperthyroid patients and the control group.
Cancer incidence, especially cancer of the stomach, kidney, and breast, was higher in patients treated with RAI for hyperthyroidism.
Cancer 06/2007; 109(10):1972-9. · 4.77 Impact Factor
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Hannu Päivä,
Juha Laakso,
Inkeri Ruokonen,
Mari Luomala,
Marika Saarela,
Tiina Solakivi, Saara Metso,
Matti Nikkilä,
Erkki Wuolijoki,
Reijo Laaksonen,
Terho Lehtimäki
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ABSTRACT: Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects.
Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA.
Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels.
There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.
Clinica Chimica Acta 10/2006; 371(1-2):97-101. · 2.54 Impact Factor
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Duodecim; lääketieteellinen aikakauskirja 02/2006; 122(21):2643-5.
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Terho Lehtimäki,
Petri Ojala,
Riikka Rontu,
Sirkka Goebeler,
Pekka J Karhunen,
Marja Jylhä,
Kari Mattila, Saara Metso,
Hannu Jokela,
Matti Nikkilä,
Erkki Wuolijoki,
Antti Hervonen,
Mikko Hurme
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ABSTRACT: To establish whether the relationship between interleukin-6 (IL-6) and plasma lipid and C-reactive protein (CRP) concentrations is different in Finnish nonagenarians than in middle-aged subjects with lower inflammatory status.
Cross-sectional.
Observational cohort study concentrating on the oldest old.
Nonagenarians (n=291, mean age+/-standard deviation 90+/-1; 68 men, 223 women) who lived in the Tampere municipality in southern Finland and a middle-aged control population from the same area (n=227, aged 44+/-8).
Plasma high sensitive CRP and lipid concentrations were analyzed using an automatic analyzer and IL-6 levels using enzyme-linked immunosorbent assay.
Plasma concentrations of IL-6 (4.39+/-5.25 vs 1.88+/-1.98 pg/mL) and CRP (3.54+/-4.98 vs 1.53+/-1.91 mg/L) were significantly higher in nonagenarians than in middle-aged subjects (P<.001). In nonagenarians, plasma CRP levels increased (P<.001) and plasma total cholesterol (P=.006), low-density lipoprotein cholesterol (P=.02), and high-density lipoprotein cholesterol (P=.002) levels decreased according to IL-6 quartiles. In middle-aged subjects, similar associations were not found.
The relationship between IL-6 and plasma CRP and cholesterol levels in nonagenarians with enhanced systemic inflammation differs from that of middle-aged subjects.
Journal of the American Geriatrics Society 10/2005; 53(9):1552-8. · 3.74 Impact Factor
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ABSTRACT: Chitosan is a deacetylated product of chitin. Microcrystalline form of chitosan has a large adsorption area claimed to decrease gastrointestinal absorption of cholesterol. However, the long-term effect of chitosan on plasma lipids is variable, the averaged influence being negligible or lacking in mildly-to-moderately hypercholesterolaemic (4.8-6.8 mmol/l) subjects. We evaluated whether this variation and inefficacy depend on apolipoprotein E genotype. 130 middle-aged, otherwise healthy men (n=55) and women (n=75) were randomized into two treatment groups for a 7 month trial. During a 1 month run-in period all participants received placebo. Subsequently, one half first took placebo twice daily for 3 months and then 1.2 g chitosan twice daily for 3 months, and the other half vice versa in a cross-over way. Altogether 84 participants completed the study. Plasma lipids and glucose were determined at the end of each phase of the study, and all subjects undergone to the cross-over phases were apolipoprotein E genotyped. Chitosan altered plasma total, low- and high density cholesterol, triglycerides, and blood glucose in neither apolipoprotein E epsilon 4 allele carriers (n=29) nor non-carriers (n=55), compared to placebo. In conclusions, chitosan is ineffective to decrease plasma lipids in apolipoprotein E epsilon 4 carrier and non-carrier phenotypes with mildly-to-moderately increased plasma cholesterol.
Basic & Clinical Pharmacology & Toxicology 09/2005; 97(2):98-103. · 2.18 Impact Factor
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Terho Lehtimäki,
Petri Ojala,
Riikka Rontu,
Sirkka Goebeler,
Pekka J. Karhunen,
Marja Jylhä,
Kari Mattila, Saara Metso,
Hannu Jokela,
Matti Nikkilä,
Erkki Wuolijoki,
Antti Hervonen,
Mikko Hurme
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ABSTRACT: Objectives: To establish whether the relationship between interleukin-6 (IL-6) and plasma lipid and C-reactive protein (CRP) concentrations is different in Finnish nonagenarians than in middle-aged subjects with lower inflammatory status.Design: Cross-sectional.Setting: Observational cohort study concentrating on the oldest old.Participants: Nonagenarians (n=291, mean age±standard deviation 90±1; 68 men, 223 women) who lived in the Tampere municipality in southern Finland and a middle-aged control population from the same area (n=227, aged 44±8).Measurements: Plasma high sensitive CRP and lipid concentrations were analyzed using an automatic analyzer and IL-6 levels using enzyme-linked immunosorbent assay.Results: Plasma concentrations of IL-6 (4.39±5.25 vs 1.88±1.98 pg/mL) and CRP (3.54±4.98 vs 1.53±1.91 mg/L) were significantly higher in nonagenarians than in middle-aged subjects (P<.001). In nonagenarians, plasma CRP levels increased (P<.001) and plasma total cholesterol (P=.006), low-density lipoprotein cholesterol (P=.02), and high-density lipoprotein cholesterol (P=.002) levels decreased according to IL-6 quartiles. In middle-aged subjects, similar associations were not found.Conclusion: The relationship between IL-6 and plasma CRP and cholesterol levels in nonagenarians with enhanced systemic inflammation differs from that of middle-aged subjects.
Journal of the American Geriatrics Society 07/2005; 53(9):1552 - 1558. · 3.74 Impact Factor
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ABSTRACT: Antibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n = 51) and without (n = 35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p < 0.0001). The area under the ROC plot was 0.822 (95% CI, 0.727 to 0.918) for the antibody titer and 0.769 (95% CI, 0.661 to 0.876) for the HDL cholesterol concentration. Both the antibody titer and the plasma HDL cholesterol level were more accurate markers of CAD than the LDL cholesterol level. As a conclusion, our results indicate that the antibody titer against MDA-modified LDL discriminates between subjects with widespread CAD and those without CAD similarly as the HDL cholesterol concentration. Moreover, the antibody titer against MDA-modified LDL is inversely correlated with the risk of severe CAD.
Clinical Chemistry and Laboratory Medicine 01/2005; 43(4):357-60. · 2.15 Impact Factor
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ABSTRACT: To determine the cumulative incidence of hypothyroidism during long-term follow-up in patients treated for hyperthyroidism by radioactive iodine (131)I (RAI) therapy, the significance of clinical factors in predicting the development of hypothyroidism, and the outcome after a fixed 7 mCi (259 MBq) dose of RAI.
Prospective cohort study of patients treated for hyperthyroidism by RAI.
Since 1965, details on 2043 patients treated by RAI therapy in Tampere University Hospital were entered into a computerized register. Following RAI treatment, thyroid status was monitored every 1-3 months during the first year, and subsequently at 1-3-year intervals until June 2002 or until the patient died or moved out of the Tampere University Hospital district. results The cumulative incidence of hypothyroidism in patients with Graves' disease and toxic multinodular goitre at 1, 10 and 25 years was 24%vs. 4%, 59%vs. 15% and 82%vs. 32%, respectively. In a Cox regression model, previous partial thyroidectomy [risk ratio (RR) = 1.63 in patients with Graves' disease and RR = 1.59 in those with toxic multinodular goitre] and age at the first RAI treatment (RR = 0.998 and RR = 0.996 per year) were statistically significantly associated with the development of hypothyroidism both in patients with Graves' disease and in those with toxic multinodular goitre. Antithyroid medication preceding RAI therapy (RR = 0.47) decreased and female gender (RR = 1.53) increased the risk of hypothyroidism only in patients with Graves' disease. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 75% of patients, while two to six RAI treatments were needed in 25% of patients to achieve either a hypothyroid or a euthyroid state in both groups. None of the clinical factors studied was associated with the remission rate either in patients with Graves' disease or in those with toxic multinodular goitre. The remission rate did not differ between the patients who received a dose of RAI calculated according to the uptake of RAI and thyroid size and those who received an empirical dose of RAI. The fixed 7 mCi (259 MBq) dose of RAI cured 80% of patients.
RAI treatment is effective in treating hyperthyroidism in patients with Graves' disease, but hypothyroidism will develop in 82% of patients in 25 years. Because the development of hypothyroidism seems to be inevitable and unpredictable by any clinical factors, the objective of RAI treatment should be to minimize the persistence of hyperthyroidism with the simplest possible form of treatment. We recommend a fixed 7 mCi dose of RAI to be used as the first empirical dose in the treatment of hyperthyroidism, at least in Graves' disease.
Clinical Endocrinology 12/2004; 61(5):641-8. · 3.17 Impact Factor
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ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor that participates in the regulation of vasodilatory function and is also linked to hypertension, whereas its stereoisomere, symmetric dimethylarginine (SDMA), is biologically inactive. Dietary components influence vascular functions and a high-fat meal seems to increase postprandial plasma ADMA levels. However, it has not been published whether diet influences plasma ADMA levels. In this study, we investigated the impact of diet on plasma ADMA and SDMA levels. Thirty-four mildly hypercholesterolemic, otherwise healthy women (n = 14) and men (n = 20) with a mean age of 46.2 years (range, 35 to 62 years) participated in the study. The subjects were examined twice at intervals of 2 months. Seven-day food records were used to analyze diet and alcohol intake. ADMA was measured by using high-performance liquid chromatography (HPLC)-tandem mass spectrometry. In a multivariate analysis (R2 = 0.20, P < .002), low amount of energy received from carbohydrates (r = -0.31, P = .009) and high plasma triglycerides (r = 0.30, P = .01) were predictors of high ADMA plasma levels. Alcohol drinkers had higher plasma ADMA concentrations than abstainers (0.50 +/- 0.13 v 0.42 +/- 0.11 micromol/L, P = .04). Plasma ADMA correlated with systolic (r = 0.60, P = .005) and diastolic blood pressure (r = 0.53, P = .02) in abstainers but not in alcohol drinkers. Plasma SDMA was not associated with any dietary components or with blood pressure. In conclusion, a high amount of dietary carbohydrates is strongly associated with low levels of plasma ADMA. Concentration of ADMA in plasma seems to be higher in alcohol drinkers than in abstainers.
Metabolism 08/2004; 53(8):1072-5. · 2.66 Impact Factor
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ABSTRACT: To evaluate the long-term effect of microcrystalline chitosan (MCC) on plasma lipids, especially the concentration of low-density lipoprotein (LDL) cholesterol, in subjects with a moderately increased concentration of plasma total cholesterol.
A total of 130 middle-aged men and women without severe disease and with a total cholesterol of 4.8-6.8 mmol/l and triglycerides below 3.0 mmol/l were randomised into two treatment groups. At the beginning of the 10-month trial, all participants received placebo 1.2 g twice daily during a 1-month run-in period. Subsequently, group 1 first received 1.2 g placebo twice daily for 3 months and then 1.2 g MCC twice daily for 3 months. Correspondingly, group 2 received 1.2 g MCC twice daily during the first and 1.2 g placebo twice daily during the second 3-month period. During the final 3-month follow-up period, both groups received MCC. Altogether, 83 participants completed the study.
No difference was detected in the change in the LDL-cholesterol concentration between the treatments during the crossover trial ( P=0.98 for interaction between time period and treatment group, repeated-measures analysis of variance for crossover design). In an otherwise similar analysis, no differences were detected between the treatments in the concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose.
Treatment with MCC had no effect on the concentrations of plasma lipids or glucose in healthy middle-aged men and women with moderately increased plasma cholesterol concentrations.
European Journal of Clinical Pharmacology 01/2004; 59(10):741-6. · 2.85 Impact Factor
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ABSTRACT: Oxidized low-density lipoprotein (LDL) autoantibodies (oxLDLab), apolipoprotein E (apoE) phenotype, postprandial triglyceride changes and LDL size are suggested to be risk factors for coronary artery disease (CAD). Our aim was to study the interaction between these new risk factors among patients with CAD and healthy controls.
oxLDLab from 31 men with angiographically verified CAD and 31 healthy men were analyzed by enzyme-linked immunosorbent assay. Isoelectric focusing and immunoblotting were used for apoE phenotyping. Triglyceride level was measured after 12 h of fasting and 3, 5 and 7 h after a high-fat meal. Nondenaturing gradient gel electrophoresis was used to separate LDL particles according to size.
oxLD- Lab levels increased according to apoE phenotype in the following order: E2 < E3 < E4 (p = 0.004, ANOVA). The postprandial response of triglycerides, the size of LDL particles and the concentration of LDL and high-density lipoprotein (HDL) cholesterol did not differ between apoE phenotypes, and the use of these variables as covariates did not change the statistically significant difference in oxLDLab levels between apoE phenotypes (p = 0.01, ANCOVA). oxLDLab levels did not differ between the patient and control groups.
We found an association between apoE allele epsilon2 and decreased levels of oxLDLab, which was independent of the postprandial response of triglycerides, the size of LDL particles and plasma LDL and HDL cholesterol levels. The mechanism by which apoE affects oxidation of LDL remains unknown.
Journal of Biomedical Science 10(3):345-51. · 2.01 Impact Factor
