Genetic Variation of 'Candidatus Liberibacter solanacearum' Haplotype C and Identification of a Novel Haplotype from Trioza urticae and Stinging Nettle.

'Candidatus Liberibacter solanacearum' (CLso) haplotype C is associated with disease in carrots and transmitted by the carrot psyllid Trioza apicalis. To identify possible other sources and vectors of this pathogen in Finland, samples were taken of wild plants within and near the carrot fields, the psyllids feeding on these plants, parsnips growing next to carrots, and carrot seeds. For analyzing the genotype of the CLso-positive samples, a multilocus sequence typing (MLST) scheme was developed. CLso haplotype C was detected in 11% of the T. anthrisci samples, in 35% of the Anthriscus sylvestris plants with discoloration, and in parsnips showing leaf discoloration. MLST revealed that the CLso in T. anthrisci and most A. sylvestris plants represent different strains than the bacteria found in T. apicalis and the cultivated plants. CLso haplotype D was detected in 2 of the 34 carrot seed lots tested, but was not detected in the plants grown from these seeds. Phylogenetic analysis by unweighted-pair group method with arithmetic means clustering suggested that haplotype D is more closely related to haplotype A than to C. A novel, sixth haplotype of CLso, most closely related to A and D, was found in the psyllid T. urticae and stinging nettle (Urtica dioica, Urticaceae), and named haplotype U.

High vitreous concentration of IL-6 and IL-8, but not of adhesion molecules in relation to plasma concentrations in proliferative diabetic retinopathy.

BACKGROUND/AIM: Inflammatory markers have been observed in proliferative diabetic retinopathy (PDR). We assessed vitreous concentrations of adhesion molecules and cytokines in PDR and non-diabetic controls and plasma concentrations to differentiate local inflammation from the breakdown of the blood-retina barrier. METHODS: 38 patients with PDR and 16 controls with macular hole or epiretinal membrane underwent vitrectomy. Vitreous and plasma soluble adhesion molecules [sE-selectin, intercellular adhesion molecule (sICAM)-1 and -3, platelet-endothelial cell adhesion molecule (sPECAM)-1, sP-selectin, vascular cell adhesion molecule (sVCAM)-1] and cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 (p70), tumour necrosis factor-α and -ß, γ-interferon] were detected by the multiplex assay. RESULTS: Levels of IL-6 and IL-8 were 26-fold (p = 0.001) and 6-fold higher (p = 0.001) in vitreous than in plasma in PDR. Vitreous IL-10 (p = 0.004), sPECAM-1, sE-selectin, sICAM-1 and sVCAM-1 were higher in PDR than controls (p = 0.001 for all). Adhesion molecule concentrations in vitreous in PDR were less than 10% of those in plasma. IL-10 was lower in vitreous than plasma (3.0 vs. 12.8 pg/ml, p = 0.007), and the vitreous IL-10/IL-8 ratio was significantly lower in PDR than in controls (0.10 vs. 0.55 pg/ml, p = 0.003). CONCLUSION: The elevated IL-6 and IL-8 levels in vitreous, but not in plasma, are evidence favouring local over systemic inflammation in PDR. Furthermore, there was imbalance between inflammatory and anti-inflammatory cytokines in the vitreous.

Oral, transdermal and vaginal combined contraceptives induce an increase in markers of chronic inflammation and impair insulin sensitivity in young healthy normal-weight women: a randomized study.

STUDY QUESTION: What is the effect of alternative administration routes of combined contraceptives (CCs) on androgen secretion, chronic inflammation, glucose tolerance and lipid profile? SUMMARY ANSWER: The use of oral, transdermal and vaginal CCs impairs glucose tolerance and induces chronic inflammation. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Oral CCs worsen insulin sensitivity and are associated with increased levels of circulating inflammatory markers, whereas the metabolic effects of transdermal and vaginal CCs have been reported to be minimal. This is the first study comparing three different administration routes of CCs on metabolic variables. STUDY DESIGN, SIZE AND DURATION: This randomized (computer-generated) open-label 9-week follow-up study was conducted at the Oulu University Hospital, Finland. Fasting blood samples were collected at baseline and thereafter at 5 and 9 weeks of treatment, and serum levels of 17-hydroxyprogesterone, androstenedione, testosterone, C-reactive protein (CRP), sex hormone-binding globulin (SHBG), glucose, insulin, C-peptide, total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were measured. Oral glucose tolerance tests were performed and plasma levels of pentraxin 3 (PTX-3) were measured at 0 and 9 weeks. The randomization list, with an allocation ratio of 1:1:1 and block size of six, was computer generated and constructed by a pharmacist at the Oulu University Hospital. The research nurse controlled the randomization list and assigned participants to their groups at the first visit. PARTICIPANTS AND SETTING: Forty-two of 54 healthy women who entered the study used oral contraceptive pills (n = 13), transdermal contraceptive patches (n = 15) or contraceptive vaginal rings (n = 14) continuously for 9 weeks. Inclusion criteria were regular menstrual cycles, at least a 2-month washout as regards hormonal contraceptives and no medication. MAIN RESULTS AND THE ROLE OF CHANCE: Serum levels of SHBG increased and consequently the free androgen index (FAI) decreased in all study groups from baseline to 9 weeks of treatment [FAI, oral: 1.3 (95% confidence interval, CI: 0.94; 1.62) to 0.40 (0.25; 0.54); transdermal: 1.2 (0.96; 1.4) to 0.36 (0.30; 0.43); vaginal: 1.6 (1.1; 2.1) to 0.43 (0.29; 0.58), P < 0.001 in all groups]. Insulin sensitivity was reduced at 9 weeks in all three groups according to the Matsuda index [oral: 7.3 (5.5; 9.0) to 5.6 (3.9; 7.3); transdermal: 9.1 (6.7; 11.4) to 6.6 (4.5; 8.8); vaginal: 7.7 (5.9; 9.5) to 5.4 (3.9; 7.0), P= 0.004-0.024]. Levels of HDL cholesterol, triglycerides and CRP rose in all three groups [CRP, oral: 0.70 (0.38; 1.0) to 5.4 (1.0; 9.9) mg/l; transdermal: 0.77 (0.45; 1.1) to 2.9 (1.4;4.4) mg/l; vaginal: 0.98 (0.52; 1.4) to 3.7 (-0.25; 7.7, a negative value due to skewed distribution to right) mg/l, P≤ 0.002 in all groups] and PTX-3 levels increased in the oral and transdermal study groups (P = 0.007 and P = 0.002). WIDER IMPLICATIONS OF THE FINDINGS: Although the long-term consequences of the present results remain undetermined, these findings emphasize the importance of monitoring glucose metabolism during the use of CCs, especially in women with known risks of type 2 diabetes or cardiovascular diseases. BIAS, LIMITATIONS, GENERALIZABILITY: The number of subjects was relatively low. Moreover, the 9-week exposure to CCs is too short to draw conclusions about the long-term health consequences. However, as the subjects were healthy, normal-weight young women, the possible alterations in the glucose and inflammatory profiles among women with known metabolic risks might be even greater. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Academy of Finland, the Sigrid Jusélius Foundation, the Finnish Medical Foundation, the Research Foundation of Obstetrics and Gynecology, Oulu University Scholarship Foundation, the North Ostrobothnia Regional Fund of the Finnish Cultural Foundation, the Tyyni Tani Foundation of the University of Oulu and the Finnish-Norwegian Medical Foundation. No competing interests. TRIAL REGISTRATION NUMBER: NCT01087879.

First Report of "Candidatus Liberibacter solanacearum" Associated with Psyllid-Affected Carrots in Sweden.

Carrot (Daucus carota) plants with symptoms resembling those associated with the carrot psyllid Trioza apicalis and the bacterium "Candidatus Liberibacter solanacearum" (1-4) were observed in 70% of commercial fields in southern Sweden in August 2011, with approximately 1 to 45% symptomatic plants per field. T. apicalis, a pest of carrot in northern and central Europe, including Sweden, can cause as much as 100% crop loss and is associated with "Ca. L. solanacearum" (1-4). Symptoms on affected plants include leaf curling, yellow and purple discoloration of leaves, stunted growth of shoots and roots, and proliferation of secondary roots (3). Carrot plant and psyllid samples were collected from fields in the province of Halland. Total DNA was extracted from petiole and root tissues of 33 symptomatic and 16 asymptomatic plants (cvs. Nevis and Florida), with the cetyltrimethylammonium bromide (CTAB) buffer extraction method (2,3). DNA was also extracted from 155 psyllids (3). DNA samples were tested by PCR using primer pairs OA2/OI2c (5''-GCGCTTATTTTTAATAGGAGCGGCA-3'/5'-GCCTCGCGACTTCGCAACCCAT-3') and CL514F/R (5'-CTCTAAGATTTCGGTTGGTT-3'/5'-TATATCTATCGTTGCACCAG-3'), to amplify a portion of 16S rDNA and rplJ/rplL ribosomal protein genes, respectively, of "Ca. L. solanacearum" (2,3). A 1,168-bp 16S rDNA fragment was detected in the DNA from all 33 symptomatic and two asymptomatic plants, and a 668-bp rplJ/rplL fragment was amplified from the DNA of all 33 symptomatic and four asymptomatic plants, indicating the presence of liberibacter. DNA from 23 and 49 psyllid samples yielded similar amplicons with OA2/OI2c and CL514F/R primer pairs, respectively. Amplicons from the DNA of four carrot roots and three T. apicalis with each primer pair were cloned (pCR2.1-TOPO; Invitrogen, Carlsbad, CA) and three clones of each of the 14 amplicons were sequenced (MCLAB, San Francisco, CA). BLAST analysis of the 16S rDNA consensus sequences from carrot (GenBank Accession No. JN863095) and T. apicalis (GenBank Accession No. NJ863096) showed 100% identity to those of "Ca. L. solanacearum" previously amplified from carrot (GU373048 and GU373049) and T. apicalis (GU477254 and GU477255) from Finland (2,3). The rplJ/rplL consensus sequences from carrot (GenBank Accession No. JN863093) and T. apicalis (GenBank Accession No. JN863094) were 99% identical to the sequences of rplJ/rplL "Ca. L. solanacearum" ribosomal protein gene from carrots in Finland (GU373050 and GU373051). To our knowledge, this is the first report of "Ca. L. solanacearum" associated with carrot and T. apicalis in Sweden. The disease associated with this bacterium caused millions of dollars in losses to potato and several other solanaceous crops in North and Central America and New Zealand (1). This plant pathogen is also associated with significant economic damage to carrot crops observed in Finland (2,3). References: (1) J. E. Munyaneza. Southwest. Entomol. 35:471, 2010. (2) J. E. Munyaneza et al. Plant Dis. 94:639, 2010. (3) J. E. Munyaneza et al. J. Econ. Entomol. 103:1060, 2010. (4) A. Nissinen et al. Entomol. Exp. Appl. 125:277, 2007.

Midlife smoking, apolipoprotein E and risk of dementia and Alzheimer's disease: a population-based cardiovascular risk factors, aging and dementia study.

AIM: To elucidate the effect of midlife smoking on the risk of dementia and Alzheimer's disease (AD), and the possible modification of this relation by the apolipoprotein E (APOE) ε4. METHODS: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were randomly selected from population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). After an average follow-up of 21 years, 1,449 persons (73%) aged 65-79 years took part in a reexamination in 1998. RESULTS: Smoking in midlife increased the risk of dementia (odds ratio, OR: 4.93; 95% CI: 1.51-16.11) and AD (OR: 6.56; 95% CI: 1.80-23.94) among the APOE ε4 carriers, but not among the APOE ε4 noncarriers. CONCLUSION: Midlife smoking was associated with an increased risk of dementia and AD later in life only among those individuals carrying the APOE ε4 allele. These results suggest that the association between smoking and AD may be complex and vary according to genotype.

First Report of "Candidatus Liberibacter solanacearum" Associated with Psyllid-Affected Carrots in Europe.

Carrot (Daucus carota) plants with symptoms resembling those of carrot psyllid (Trioza apicalis) damage (3,4) were observed in 14 commercial fields in southern Finland in August 2008; all cultivars grown were affected at approximately 5 to 35% symptomatic plants per field. T. apicalis, a pest of carrots in northern and central Europe, can cause up to 100% crop loss (3,4). Symptoms on affected plants included leaf curling, yellow and purple discoloration of leaves, stunted growth of shoots and roots, and proliferation of secondary roots (3,4). Given recent association of liberibacter with several annual crops affected by psyllids (1,2), an investigation on whether this bacterium is associated with symptoms of psyllid damage on carrots was conducted. Total DNA was extracted from petiole tissue of 20 symptomatic and 18 asymptomatic plants (cv. Maestro, Nanda, Nipomo, Nerac, and Fontana) sampled from 10 psyllid-infested fields in southern Finland, as well as 15 plants (cv. Primecut, Cheyenne, and Triple Play) grown from seed in an insect-free greenhouse, with the cetyltrimethylammoniumbromide (CTAB) method (2). DNA was also extracted from 10 carrot roots (cv. Nantura) of plants continuously exposed to field-collected carrot psyllid colonies in the laboratory. DNA samples were tested by PCR using primer pairs OA2/OI2c and CL514F/R to amplify a portion of 16S rDNA and rplJ/rplL ribosomal protein genes, respectively, of "Candidatus Liberibacter solanacearum" (1,2). A 1,168 bp 16S rDNA fragment was detected in DNA from 1 asymptomatic and 16 symptomatic plants and a 669 bp rplJ/rplL fragment was amplified from DNA from 19 symptomatic and 6 asymptomatic plants, indicating presence of liberibacter. DNA from all 10 root samples yielded similar amplicons with both primer pairs. DNA from all the greenhouse carrot plants yielded no amplicon. Amplicons from DNA from three petioles and three roots with each primer pair were cloned (pCR2.1-TOPO; Invitrogen, Carlsbad, CA) and three clones of each of the 12 amplicons were sequenced (MCLAB, San Francisco, CA). BLAST analysis of the 16S rDNA consensus sequences from petiole and root tissues (GenBank Accession Nos. GU373049 and GU373048, respectively) showed 99.9% identity to those of "Ca. L. solanacearum" amplified from Capsicum annuum (FJ957896) and Solanum lycopersicum (FJ957897) from Mexico, and "Ca. L. psyllaurous" from potato psyllids (EU812559). The rplJ/rplL consensus sequences from petioles and roots (GenBank Accession Nos. GU373051 and GU373050, respectively) were 97.9% identical to the analogous rplJ/rplL "Ca. L. solanacearum" ribosomal protein gene sequence from solanaceous crops in New Zealand (EU834131) and to "Ca. Liberibacter" sp. sequence from zebra chip-affected potatoes in California (FJ498803). To our knowledge, this is the first report of "Ca. L. solanacearum" associated with a nonsolanaceous species and the first report of this pathogen outside of North and Central America and New Zealand (1,2). References: (1) L. W. Liefting et al. Plant Dis. 93:208, 2009. (2) J. E. Munyaneza et al. Plant Dis. 93:552, 2009. (3) G. Nehlin et al. J. Chem. Ecol. 20:771, 1994. (4) A. Nissinen et al. Entomol. Exp. Appl. 125:277, 2007.

Point-of-care testing of group A streptococcal antigen: performance evaluated by external quality assessment.

The purpose of this study was to evaluate the overall performance of rapid antigen detection (RAD) in group A streptococcus (GAS) in Finland by using the results of external quality assurance (EQA) samples. We also compared the performance of laboratory professionals to that of nursing professionals. Around 22,800 EQA results among a total of 383 laboratories and physician's offices were analysed. Vocational data on the personnel who carried out the tests were available for 10,088 EQA samples, 7,428 of which were tested by laboratory technicians and 2,531 by nursing staff. The best overall performance was found with GAS-negative samples: 99% of the reports were correct. In contrast, the overall performance was only 76% when the samples were weakly positive for GAS antigen. The laboratory technicians performed statistically significantly better than the nursing staff, with both strongly positive (correct results 98.9% vs. 95.1%, respectively; p<0.001) and weakly positive (79.3% vs. 65.3%, respectively; p<0.001) samples. With negative samples, no difference in performance between the laboratory and nursing staff was found (99.5% vs. 99.0%, respectively). The professional skills of the person performing the RAD test for GAS have a major impact on the sensitivity of the test. Based on the results of this study, we suggest that EQA-like artificial specimens could be used as a tool to improve and validate the quality of RAD testing in individual testing sites.

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease.

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD ( n = 133), stable CAD ( n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL ( P = 0.016, P = 0.043), Rgp44 ( P = 0.012, P = 0.004), Aa-HSP60 ( P = 0.032, P = 0.030), Tannerella forsythia ( P = 0.002, P = 0.004), Porphyromonas endodontalis ( P = 0.016, P = 0.020), Prevotella intermedia ( P = 0.038, P = 0.005), and with total IgA antibody concentration ( P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.

Low incidence of antibiotic resistance among invasive and nasopharyngeal isolates of Streptococcus pneumoniae from children in rural Philippines between 1994 and 2000.

The purpose of this study was to determine the prevalence of acquired antimicrobial resistance in Streptococcus pneumoniae isolated from nasopharyngeal swabs and blood and cerebrospinal fluid (CSF) specimens of 3,028 children hospitalized with signs or symptoms of pneumonia, sepsis, or meningitis in rural Philippines between 1994 and 2000. Pneumococci were identified using standard methods, serotyped, and their susceptibility to oxacillin, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole was determined using the disk diffusion method. Penicillin minimum inhibitory concentrations (MICs) of the oxacillin-resistant isolates were further tested. The clonality of the penicillin-nonsusceptible (PNSP) isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Altogether 1,048 isolates were analyzed, of which 35 were invasive and 1,013 nasopharyngeal isolates. None was resistant, but 22 (2.1%) were intermediately resistant to penicillin, 4 (0.2%) were resistant to chloramphenicol, 3 (0.2%) to erythromycin, 39 (3.7%) to tetracycline, and 4 (0.2%) to trimethoprim/sulfamethoxazole. Twelve of the 22 PNSP isolates were of serotype 14 and of sequence type 63. These included the two invasive PNSP isolates. PFGE profiling further identified three separate clusters among the sequence of type 63, serotype 14 (ST63(14)) isolates. Antimicrobial resistance in both invasive and nasopharyngeal pneumococcal pediatric isolates in rural Philippines is rare. In spite of this remote setting, the PNSP isolates of the serotype 14 clusters were of ST63 type, which has been described previously on other continents.

Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study.

BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's disease. Earlier studies have shown differences in brain structure according to the APOE epsilon4 status. OBJECTIVE: To assess possible differences in brain structure according to the APOE epsilon4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. METHODS: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. RESULTS: The SMCI epsilon4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. CONCLUSION: The rate of brain atrophy in certain brain areas may be increased in epsilon4-positive MCI subjects progressing to dementia.

Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study.

OBJECTIVE: To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective information on this association has been lacking. DESIGN, SUBJECTS AND SETTING: Six hundred and seventy six healthy men born between 1900 and 1920 from Finland, Italy and the Netherlands participated in a 10-year prospective cohort study. Cognitive functioning was assessed using the Mini-Mental State Examination (0-30 points, with a higher score indicating better cognitive performance). Coffee consumption was estimated in cups per day. A mixed longitudinal model was used to investigate the association between baseline coffee consumption and 10-year cognitive decline. Multiple adjustments were made. RESULTS: Men who consumed coffee had a 10-year cognitive decline of 1.2 points (4%). Non-consumers had an additional decline of 1.4 points (P<0.001). An inverse and J-shaped association was observed between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for three cups of coffee per day (0.6 points). This decline was 4.3 times smaller than the decline of non-consumers (P<0.001). CONCLUSIONS: Findings suggest that consuming coffee reduces cognitive decline in elderly men. An inverse and J-shaped association may exist between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for men consuming three cups of coffee per day.

Contrast enhancement in EIT imaging of the brain.

We consider electrical impedance tomography (EIT) imaging of the brain. The brain is surrounded by the poorly conducting skull which has low conductivity compared to the brain. The skull layer causes a partial shielding effect which leads to weak sensitivity for the imaging of the brain tissue. In this paper we propose an approach based on the Bayesian approximation error approach, to enhance the contrast in brain imaging. With this approach, both the (uninteresting) geometry and the conductivity of the skull are embedded in the approximation error statistics, which leads to a computationally efficient algorithm that is able to detect features such as internal haemorrhage with significantly increased sensitivity and specificity. We evaluate the approach with simulations and phantom data.

Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.

Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28-31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z-score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors of coronary heart disease and total mortality among elderly men with and without preexisting coronary heart disease. Finnish cohorts of the Seven Countries Study.

OBJECTIVES: We attempted to determine whether elevated levels of the classic coronary heart disease risk factors are associated with increased coronary risk and all-cause mortality among elderly men with and without coronary heart disease at baseline. BACKGROUND: The strength of any association between the classic coronary risk factors and survival among elderly men with and without coronary heart disease has not been established. METHODS: The classic coronary risk factor levels and risk of coronary events and total mortality during a 5-year follow-up interval were studied among men aged 65 to 84 years. Coronary events were fatal myocardial infarction (n = 71), any myocardial infarction (n = 96) and, among the men without disease, other nonfatal coronary heart disease events (n = 80). RESULTS: Among the 171 men with prevalent coronary heart disease, significant (p < 0.05) risk factors for fatal myocardial infarction (n = 42) in multivariate analyses were low high density lipoprotein cholesterol (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1 to 0.8 for 1-mmol/liter increase), high ratio of total to high density lipoprotein cholesterol (OR 1.4, 95% CI 1.1 to 1.7 for 1-U increase), and smoking more than nine cigarettes daily (OR 6.0, 95% CI 1.5 to 24.9 vs. values in men who had never smoked). Among the 476 men without prevalent coronary heart disease, only high serum total cholesterol was a risk factor for fatal myocardial infarction (n = 29) (OR 1.4, 95% CI 1.0 to 2.0 for 1-mmol/liter increase). Among men with prevalent coronary heart disease, the only significant (p < 0.05) risk factor for total mortality was smoking more than nine cigarettes daily (OR 3.9, 95% CI 1.1 to 13.4 vs. values among men who had never smoked). Among men without prevalent coronary heart disease, only the use of antihypertensive medication (OR 2.0, 95% CI 1.2 to 3.3 between men with and without such medication) was a risk factor for total mortality. CONCLUSIONS: The classic risk factors for coronary heart disease appear to be of importance even in old age, especially among men with prevalent coronary heart disease.

Cancer pattern among hypertensive patients in North Karelia, Finland.

The objective of this study was to determine the site-specific cancer incidence of hypertensive patients and examine the effect of blood pressure-related variables on the risk of cancers with elevated incidence among the hypertensive patients. A record linkage study of Hypertension Register of the North Karelia Project and the Finnish Cancer Registry was conducted. The mean follow-up time was 16 years. A total of 20 529 hypertensive patients were studied. Main outcome measures were standardised incidence ratios and hazard ratios. The overall cancer incidence was close to that of the general population for both men and women. The incidence rate for the kidney cancer was significantly increased in hypertensive patients (standardised incidence ratio 1.34, 95% confidence interval (CI) 1.11-1.60), as well as incidence rates for cancers of pancreas (1.26, 1.02-1.54), and endometrium (1.22, 1.01-1.44) in hypertensive women. The incidence of lung cancer was significantly decreased (0.86, 0.77-0.95). The incidence of liver cancer was elevated with borderline significance (1.36, 0.99-1.82). In Cox regression models, the use of antihypertensive drugs at baseline was a significant predictor of kidney (hazard ratio for use of antihypertensive drugs 1.89, 95% CI 0.96-3.75) and pancreatic cancer (1.78, 0.99-3.22) in women but not in men. The incidence of endometrial cancer or liver cancer was not related to blood pressure levels or the use of antihypertensive drugs. In women, obesity was a significant predictor of cancers of the endometrium, kidney and liver. In conclusion, increased occurrence of some cancer types among hypertensive patients seem to be partly explained by obesity and the use of antihypertensive drugs.

Serum cholesterol and risk of accidental or violent death in a 25-year follow-up. The Finnish cohorts of the Seven Countries Study.

In the two most recent cholesterol-lowering drug trials, the achieved reductions in coronary heart disease mortality were offset by increases in mortality due to accidents and violence. A possible biochemical explanation has been suggested for an association between low serum cholesterol level and increased risk of death due to injury. We, therefore, examined the association between serum cholesterol level and risk of death from accidents or violence in the 25-year follow-up of two cohorts of Finnish men (N = 1580). Although a statistically nonsignificant, negative association was observed in one cohort (hazard ratio, 0.84, with a 1 mmol/L increase in cholesterol), the other cohort showed a statistically significant, positive association in multivariate analysis (hazard ratio, 1.39). We conclude that the observed associations between serum cholesterol and deaths from injury in the present study and in cholesterol-lowering trials are probably determined by other, presently unknown factors, or by chance.

Cigarette smoking and mortality risk: twenty-five-year follow-up of the Seven Countries Study.

BACKGROUND: Although most observations in the Seven Countries Study suggest that cigarette smoking is harmful for health, universality of this conclusion remains controversial. SUBJECTS AND METHODS: Cohort-specific and pooled smoking habits at baseline (1957-1964) in 12 763 men aged 40 through 59 years living in Europe, the United States, and Japan in relation to 25-year mortality follow-up. Pooled hazard ratios for smokers vs never smokers were calculated by the Cox proportional hazards model, adjusting for baseline country of residence, age, body mass index, serum cholesterol, systolic blood pressure, and clinical cardiovascular disease. RESULTS: Adjusted hazard ratios for all-causes death in smokers compared with never smokers were 1.3 (95% confidence interval, 1.2-1.4) for smokers of less than 10 cigarettes per day and 1.8 (95% confidence interval, 1.7-1.9) for smokers of 10 cigarettes per day or more. Hazard ratios were elevated for death due to coronary heart disease, all stroke, other arterial disease, lung cancer, other cancer, chronic obstructive pulmonary disease, and other disease in smokers compared with never smokers. Within country, a few instances in which never smokers had a higher cause-specific death rate than smokers of 10 cigarettes per day or more were attributable to random variation associated with low prevalence of never smokers and multiple comparisons. CONCLUSIONS: These findings confirm the association of cigarette smoking with elevated risk of mortality from all causes, several cardiovascular diseases, cancer, and chronic obstructive pulmonary disease. Risk associated with cigarette smoking is independent of culture.

Smoking and the risk of diabetes in elderly Finnish men. Retrospective analysis of data from a 30-year follow-up study.

OBJECTIVE: To assess the association of smoking with the risk of glucose intolerance (diabetes plus impaired glucose tolerance). RESEARCH DESIGN AND METHODS: A cohort consisting of 1,711 Finnish men born in 1900-1919 were followed up from 1959 to 1994. Smoking status was assessed in a similar way at each of the six surveys from 1959 to 1989, and subjects were classified as never, former, or current smokers. Diagnosis of diabetes and impaired glucose tolerance was made according to the oral glucose tolerance tests made in 1984 and 1989, and the 1985 World Health Organization criteria was applied. RESULTS: Association between smoking and glucose intolerance was estimated separately for 420 participants and 243 nonparticipants in 1989. Multiple logistic regression analyses show that odds ratios of glucose intolerance in 1984 for current smokers in 1984 were 0.36 (0.19-0.70) and 1.20 (0.52-2.78), respectively, in the participants and the nonparticipants in 1989. Among the nonparticipants in 1989, the odds ratio for current smokers in 1969 was 2.23 (1.00-4.96). A reduced risk of glucose intolerance in 1989 associated with smoking in the participants in 1989 was found to be significant from the beginning of the follow-up. The participants in 1989 were generally healthier and had a longer life expectancy than the nonparticipants in 1989. CONCLUSIONS: In a retrospective study of men, an increased risk of diabetes and impaired glucose tolerance in smokers was found among the nonparticipants, but a reduced risk was found among the participants in 1989. The difference observed might be attributed to the fact that the participants were constitutionally different from the nonparticipants.

Ultrasonographic manifestations of carotid atherosclerosis and glucose intolerance in elderly eastern Finnish men.

OBJECTIVE: To study the association of ultrasonographic manifestations of common carotid atherosclerosis with glucose intolerance in survivors of the cohort of men born in 1900-1919 in eastern Finland. RESEARCH DESIGN AND METHODS: Carotid ultrasonography was carried out for 182 men in 1989. Glucose tolerance status classified based on an oral glucose tolerance test in 1984 and 1989 surveys was used in both prospective and cross-sectional analyses. RESULTS: Carotid atherosclerosis was common in men aged 70-89 years. There was no significant difference in the maximal carotid intimal-medial thickness between diabetic and nondiabetic men and over different age-groups; it was 1.28, 1.33, and 1.36 mm in subjects with diabetes, impaired glucose tolerance, and normal glucose tolerance, respectively (P = 0.69). No association between the presence of a nonmineralized or a mineralized atherosclerotic lesion with diabetes was found. Fasting plasma insulin did not relate to ultrasonographically detectable atherosclerotic lesions. CONCLUSIONS: Hyperglycemia and hyperinsulinemia may not be main contributors to atherosclerosis in elderly men, partly because smoking is less common and total and LDL cholesterol concentrations are lower in diabetic men than in men with normal glucose tolerance.

Dietary factors determining diabetes and impaired glucose tolerance. A 20-year follow-up of the Finnish and Dutch cohorts of the Seven Countries Study.

OBJECTIVE: To investigate the role of diet as a predictor of glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: At the 30-year follow-up survey of the Dutch and Finnish cohorts of the Seven Countries Study, in 1989/1990, men were examined according to a standardized protocol including a 2-h oral glucose tolerance test. Information on habitual food consumption was obtained using the cross-check dietary history method. Those 338 men in whom information on habitual diet was also available 20 years earlier were included in this study. Subjects known as having diabetes in 1989/1990 were excluded from the analyses. RESULTS: Adjusting for age and cohort, the intake of total, saturated, and monounsaturated fatty acids and dietary cholesterol 20 years before diagnosis was higher in men with newly diagnosed diabetes in the survey than in men with normal or impaired glucose tolerance. After adjustment for cohort, age, past body mass index, and past energy intake, the past intake of total fat was positively associated with 2-h postload glucose level (P < 0.05). An independent inverse association with the past intake of vitamin C was observed (P < 0.05). These associations were independent of changes in the intake of fat and vitamin C during the 20-year follow-up. An increase in the consumption of vegetables and legumes, potatoes, and fish during the 20-year follow-up was inversely related with 2-h glucose level (P < 0.05). CONCLUSIONS: Although the regression coefficients were in general not very large, these results indicate that a high intake of fat, especially that of saturated fatty acids, contributes to the risk of glucose intolerance and NIDDM. Foods such as fish, potatoes, vegetables, and legumes may have a protective effect. In addition, the observed inverse association between vitamin C and glucose intolerance suggests that antioxidants may also play a role in the development of derangements in glucose metabolism.