Aini Bloigu

Elevated Circulating Levels of Inflammatory Cytokines in Patients With Abdominal Aortic Aneurysm

The basic feature in the pathogenesis of abdominal aortic aneurysm (AAA) is the degradation of extracellular matrix components. This process is induced partly by cytokines secreted from inflammatory and mesenchymal cells. Circulating levels of inflammatory cytokines were studied in AAA patients and compared with subjects suffering from atherosclerotic disease only. Furthermore, the predictive value of cytokine concentrations was evaluated for aneurysm expansion rate. Circulating levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured in 50 AAA patients (40 men, 10 women), 42 patients with coronary heart disease (CHD) (23 men, 19 women), and 38 controls whose angiogram was normal (17 men, 21 women). No differences in cytokine concentrations were found between the CHD patients and the controls. AAA disease was found to be associated with significantly higher IL-1 beta and IL-6 concentrations in both male patients (median concentrations of 19.40 pmol/L and 6.45 pmol/L, respectively) and female patients (19.26 pmol/L and 7.99 pmol/L) than in either the CHD patients or the controls (P < .005). TNF-alpha levels were slightly higher in the AAA patients (1.64 pmol/L in the males and 1.59 pmol/L in the females) than in the other groups (P < .05). IFN-gamma levels were elevated significantly in the female AAA patients (3.75 pmol/L) compared with levels found in the other female (P < .05) or male (P < .01) patient groups. The measured cytokine concentrations were not related to the size of the aneurysm or the maximal thickness of the thrombus within the aneurysm. IFN-gamma concentration showed a significant positive correlation to the aneurysm expansion (R = .37, P < .02) and negative correlation to the concentration of aminoterminal propeptide of type III procollagen during 6-month follow up (R = -.42, P < .005). The results show that circulating levels of inflammatory cytokines are elevated in patients with AAA disease, suggesting that the production of these cytokines is increased in these patients compared with CHD patients and controls. Elevated INF-gamma concentrations seem to predict an increased rate of expansion in AAA.

Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study.

CONTEXT There are only a few large prospective studies involving evaluation of the effect of maternal thyroid dysfunction on offspring and observations are inconsistent. OBJECTIVE The objective of the study was to investigate the effects of thyroid dysfunction or antibody positivity on perinatal outcome. SETTING AND PARTICIPANTS The study included prospective population-based Northern Finland Birth Cohort 1986 including 9247 singleton pregnancies. First-trimester maternal serum samples were analyzed for thyroid hormones [TSH, free T(4) (fT4)] and antibodies [thyroid-peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab)]. Mothers were classified by their hormone and antibody status into percentile categories based on laboratory data and compared accordingly. MAIN OUTCOMES Outcomes were perinatal mortality, preterm delivery, absolute and gestational age-adjusted birth weight, and absolute and relative placental weight. RESULTS The offspring of TPO-Ab- and TG-Ab-positive mothers had higher perinatal mortality, which was not affected by thyroid hormone status. Unadjusted and adjusted (for maternal age and parity) risk for increased perinatal mortality was an odds ratio of 3.1 (95% confidence interval 1.4-7.1) and 3.2 (1.4-7.1) in TPO-Ab- and 2.6 (1.1-6.2) and 2.5 (1.1-5.9) in TG-Ab-positive mothers. TPO-Ab-positive mothers had more large-for-gestational age infants (2.4 vs. 0.8%, P = 0.017), as did mothers with low TSH and high fT4 concentrations vs. reference group (6.6 vs. 2.5%, P = 0.045). Significantly higher placental weights were observed among mothers with low TSH and high fT4 or high TSH and low fT4 levels as well as among TPO-Ab-positive mothers. CONCLUSIONS First-trimester antibody positivity is a risk factor for perinatal death but not thyroid hormone status as such. Thyroid dysfunction early in pregnancy seems to affect fetal and placental growth.

Chronic Chlamydia pneumoniae Infection Is Associated With a Serum Lipid Profile Known to Be a Risk Factor for Atherosclerosis

Chlamydia pneumoniae infection has been associated with coronary heart disease. To evaluate the mechanisms of this association, we studied whether chronic C. pneumoniae infection affects serum lipid values similarly to acute infections. Triglyceride, total and HDL cholesterol concentrations, and C. pneumoniae antibodies were measured from paired serum samples of 415 Finnish males taken 3 years apart. Chronic infection, defined as persistent IgG and IgA antibodies, was found in 20%, and the antibodies were negative (IgG < 32 and IgA < 16 in both samples) in 15% of the cases studied. The serum triglyceride and total cholesterol concentrations were higher in the subjects with a chronic C. pneumoniae infection than in the subjects with no antibodies (1.23 versus 1.03 mmol/L and 6.41 versus 6.31 mmol/L, respectively). The HDL cholesterol concentrations and the ratios of HDL cholesterol to total cholesterol were significantly decreased in the subjects with chronic infection (1.24 versus 1.36 mmol/L, P = .026; and 0.19 versus 0.22, P = .018, respectively). Chronic C. pneumoniae infection seems to be associated with a serum lipid profile considered to increase the risk of atherosclerosis. This finding supports the hypothesis that infections play a role in the pathogenesis of atherosclerosis.

Risks of Overweight and Abdominal Obesity at Age 16 Years Associated With Prenatal Exposures to Maternal Prepregnancy Overweight and Gestational Diabetes Mellitus

OBJECTIVE The associations of prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus (GDM) with offspring overweight are controversial. Research estimating risk for offspring overweight due to these exposures, separately and concomitantly, is limited. RESEARCH DESIGN AND METHODS Prevalence of overweight and abdominal obesity at age 16 years and odds ratios (ORs) for prenatal exposures to maternal prepregnancy overweight and GDM were estimated in participants of the prospective longitudinal Northern Finland Birth Cohort of 1986 (N = 4,168). RESULTS The prevalence and estimates of risk for overweight and abdominal obesity were highest in those exposed to both maternal prepregnancy overweight and GDM (overweight prevalence 40% [OR 4.05], abdominal obesity prevalence 25.7% [3.82]). Even in offspring of mothers with a normal oral glucose tolerance test during pregnancy, maternal prepregnancy overweight is associated with increased risk for these outcomes (overweight prevalence 27.9% [2.56], abdominal obesity prevalence 19.5% [2.60]). In offspring of women with prepregnancy normal weight, the prevalence or risks of the outcomes were not increased by prenatal exposure to GDM. These estimates of risk were adjusted for parental prepregnancy smoking, paternal overweight, and offspring sex and size at birth. CONCLUSIONS Maternal prepregnancy overweight is an independent risk factor for offspring overweight and abdominal obesity at age 16 years. The risks are highest in offspring with concomitant prenatal exposure to maternal prepregnancy overweight and GDM, whereas the risks associated with GDM are only small.

Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life

CONTEXT Knowledge is scarce concerning the significance of thyroid dysfunction/antibodies during pregnancy in regard to pregnancy complications/later maternal morbidity. OBJECTIVE The aim of this study was to evaluate the association between maternal thyroid dysfunction/antibodies during pregnancy and pregnancy complications or later maternal hypertension, diabetes, and thyroid disease. DESIGN AND SETTING We studied a prospective population-based cohort, Northern Finland Birth Cohort 1986 (NFBC 1986), with follow-up of 20 yr. Medication and hospital discharge records were used to assess maternal morbidity to hypertension, diabetes, and thyroid diseases. PARTICIPANTS The study consisted of mothers of NFBC 1986 with early pregnancy serum samples for thyroid function and antibody analyses (n = 5805). Mothers were grouped and compared according to these test results. MAIN OUTCOME MEASURES We focused on preeclampsia and gestational diabetes during index pregnancy, later maternal hypertension, diabetes, and thyroid disease morbidity and total mortality. RESULTS Thyroid dysfunction and antibodies were not associated with pregnancy complications. Overt hypothyroidism was associated with subsequent maternal thyroid disease [hazard ratio (HR) (95% confidence interval), 17.7 (7.8-40.6)] and diabetes [6.0 (2.2-16.4)]. Subclinical hypothyroidism [3.3 (1.6-6.9)], TPO-Ab-positivity [4.2 (2.3-7.4)], and TG-Ab-positivity [3.3 (1.9-6.0)] were also associated with later thyroid disease. No association was found between thyroid dysfunction/antibodies and hypertension or overall mortality. CONCLUSIONS Thyroid dysfunction and antibodies during pregnancy seem to predict later thyroid disease. Overt hypothyroidism poses risk of diabetes.

Cold temperature and low humidity are associated with increased occurrence of respiratory tract infections.

OBJECTIVE The association between cold exposure and acute respiratory tract infections (RTIs) has remained unclear. The study examined whether the development of RTIs is potentiated by cold exposure and lowered humidity in a northern population. METHODS A population study where diagnosed RTI episodes, outdoor temperature and humidity among conscripts (n=892) were analysed. RESULTS Altogether 643 RTI episodes were diagnosed during the follow-up period. Five hundred and ninety-five episodes were upper (URTI) and 87 lower (LRTI) RTIs. The mean average daily temperature preceding any RTIs was -3.7+/-10.6; for URTI and LRTI they were -4.1+/-10.6 degrees C and -1.1+/-10.0 degrees C, respectively. Temperature was associated with common cold (p=0.017), pharyngitis (p=0.011) and LRTI (p=0.048). Absolute humidity was associated with URTI (p<0.001). A 1 degrees C decrease in temperature increased the estimated risk for URTI by 4.3% (p<0.0001), for common cold by 2.1% (p=0.004), for pharyngitis by 2.8% (p=0.019) and for LRTI by 2.1% (p=0.039). A decrease of 1g/m(-3) in absolute humidity increased the estimated risk for URTI by 10.0% (p<0.001) and for pharyngitis by 10.8% (p=0.023). The average outdoor temperature decreased during the preceding three days of the onset of any RTIs, URTI, LRTI or common cold. The temperature for the preceding 14 days also showed a linear decrease for any RTI, URTI or common cold. Absolute humidity decreased linearly during the preceding three days before the onset of common cold, and during the preceding 14 days for all RTIs, common cold and LRTI. CONCLUSIONS Cold temperature and low humidity were associated with increased occurrence of RTIs, and a decrease in temperature and humidity preceded the onset of the infections.

Serological evidence of an association between Chlamydia pneumoniae infection and lung cancer

Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this cannot be explained by active or passive smoking alone. Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates. Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers. Smoking males with lung cancer (n = 230) and their age‐ and locality‐matched controls were selected among participants of the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum samples collected with a 3‐year interval before the lung cancer diagnosis. The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody (titer ≥ 16) and immune complex (titer ≥ 4). Relative risks were estimated by odds ratios (OR) adjusted for age, locality and smoking history by a conditional logistic regression model. Markers suggesting chronic C. pneumoniae infection were present in 52% of cases and 45% of controls and hence were positively associated with the incidence of lung cancer (OR 1.6; 95% confidence interval [CI] 1.0–2.3). The incidence was especially increased in men younger than 60 years (OR 2.9; 95% CI 1.5–5.4) but not in the older age group (OR 0.9; 95% CI 0.5–1.6). Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer, corroboration from other studies with larger number of cases and longer follow‐up is needed. Int. J. Cancer 74:31–34.

Early Pregnancy Reference Intervals of Thyroid Hormone Concentrations in a Thyroid Antibody-Negative Pregnant Population

BACKGROUND Thyroid dysfunction and antibodies are increasingly recognized as risk factors during pregnancy. Thyroid function changes during pregnancy and there is a need for gestational age-specific reference intervals for thyroid hormones. The aim of this study was to calculate gestational age-specific thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) reference intervals in an iodine-sufficient thyroid antibody-negative population. METHODS The study population consisted of a large, prospective population-based cohort, the Northern Finland Birth Cohort 1986 (singleton births, n = 9362), with extensive data throughout gestation. The subjects underwent serum sampling in early pregnancy. Samples were assayed for TSH, fT4, fT3, thyroid-peroxidase, and thyroglobulin antibodies (n = 5805). All mothers with thyroid antibodies or previous thyroid diseases were excluded when calculating gestational age-specific percentile categories for TSH, fT4, and fT3. Also, associations between body mass index (BMI) and thyroid hormones were established. RESULTS The upper reference limit for TSH was 2.5 multiples of median (2.7-3.5 mU/L, depending on gestational week). The lower reference limit was as low as 0.07 mU/L. Reference intervals for fT4 rose during early pregnancy and decreased thereafter, ranging between 11-22 pmol/L. Reference intervals for fT3 were uniform throughout gestation, ranging between 3.4 and 7.0 pmol/L. BMI was associated positively with early pregnancy TSH and fT3 concentrations and negatively with fT4 concentrations. CONCLUSIONS These gestational age-specific reference intervals for thyroid hormones provide a framework for clinical decision making. Overweight and obesity are increasing problems among fertile women and they are associated with possibility of thyroid dysfunction during pregnancy.

Persistence of Antibodies to Pneumococcal Capsular Polysaccharide Vaccine in the Elderly

Persistence of antibodies to 23-valent pneumococcal vaccine was assessed among 62 subjects aged 65-88 years. IgG antibodies were measured by standardized EIA to serotypes 4, 6B, 9V, 14, 19F, and 23F before and 1 month, 1 year, and 3 years after vaccination. After satisfactory antibody responses (fold increases from 2.6 to 5.3), 3-year geometric mean concentrations (GMCs) had waned to close (for types 4, 9V, and 23F) or similar (for types 6B and 19F) to their prevaccination values. Type 14 was exceptional: 1-month GMC was 7.7-fold and 3-year GMC was 3.0-fold in comparison to the prevaccination GMC. Antibody concentrations decreased at an equal rate irrespective of serotype and age or sex of the vaccinee. The major factor predicting the persistence of antibodies above the prevaccination level was the magnitude of the original antibody response. Present results suggest that pneumococcal revaccination of the elderly may be needed as early as 3-4 years after the initial vaccination.

Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma

Background: Respiratory infections are well known triggers of asthma exacerbations, but their role in stable adult asthma remains unclear. Methods: 103 asthmatics and 30 control subjects were enrolled in the study. Sputum was induced by inhalation of 3% NaCl solution. Oropharyngeal swab specimens were obtained from the posterior wall of the oropharynx. Respiratory specimens were analysed by RT-PCR for rhinovirus, enterovirus and respiratory syncytial virus and by PCR for adenovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis. Results: Sputum samples from two of the 30 healthy controls (6.7%), five of 53 patients with mild asthma (9.4%), and eight of 50 with moderate asthma (16.0%) were positive for rhinovirus. Rhinovirus positive asthmatic subjects had more asthma symptoms and lower forced expiratory volume in 1 second (FEV1) (79% predicted) than rhinovirus negative cases (93.5% predicted; p = 0.020). Chlamydia pneumoniae PCR was positive in 11 healthy controls (36.6%), 11 mild asthmatics (20.8%), and 11 moderate asthmatics (22%), and PCR positive asthmatics had lower FEV1/FVC than negative cases (78.2% v 80.8%, p = 0.023). Bordetella pertussis PCR was positive in 30 cases: five healthy controls (16.7%), 15 mild asthmatics (28.3%), and 10 moderate asthmatics (20%). Bordetella pertussis positive individuals had lower FEV1/FVC (77.1% v 80.7%, p = 0.012) and more asthma symptoms than B pertussis negative cases. Conclusions: Rhinovirus, C pneumoniae, and B pertussis are found in the sputum or pharyngeal swab specimens of asthmatic subjects without concurrent symptoms of infection or asthma exacerbation, as well as in some healthy controls. Positivity is associated with lower lung function and more frequent asthma symptoms.