18.9.2006

Antila, M., He, Q., de Jong, C., Aarts, I., Verbakel, H., Bruisten, S., Keller, S., Haanperä, M., Mäkinen, J., Eerola, E., Viljanen, M. K., Mertsola, J. and van der Zee, A.

J Med Microbiol. 2006; 55(Pt 8): 1043-51. IF 2.414

Bordetella holmesii is a Gram-negative bacterium first identified in 1995. It can cause pertussis-like symptoms in humans. B. holmesii contains insertion sequences IS481 and IS1001, two frequently used targets in the PCR diagnosis of Bordetella pertussis and Bordetella parapertussis infections.

To investigate the prevalence of B. holmesii in Finnish and Dutch patients with pertussis-like symptoms and whether B. holmesii has caused any false-positive results in diagnostic PCRs, B. holmesii-specific real-time PCRs were developed. The Finnish methods were conventional IS481 PCR and B. holmesii-specific real-time PCR (LightCycler, Roche) targeting the B. holmesii recA gene. The Dutch methods were IS481 and IS1001 PCRs with conventional or real-time formats and B. holmesii-specific real-time PCR targeting the homologue of IS1001. Of 11,319 nasopharyngeal swabs, 2804 were collected from Finnish patients from 2000 to 2003, and 8515 from Dutch patients from 1992 to 2003. B. holmesii DNA was not found in the samples analysed.

The results suggest that B. holmesii is not among the causative agents of pertussis-like symptoms in Finnish and Dutch patients and thus does not in practice confound IS481 and IS1001 PCRs.

Efficacy and safety of food fortification with calcium among adults in Finland

Hirvonen, T., Tapanainen, H., Valsta, L., Hannila, M. L., Aro, A. and Pietinen, P.

Public Health Nutrition. 2006; 9(6): 792-797. Article. IF 1.918

Objective To examine the efficacy and safety of foods fortified with calcium in the adult population in Finland.

Design A simulation study based on the FINDIET 2002 Survey, which estimated habitual food consumption, dietary supplement use and nutrient intakes using 48-hour recall and two 3-day food records, and an Internet survey of the consumption of fortified foods and dietary supplements.

Setting/participants Participants of FINDIET 2002 were 25-64 years old from five areas (n=2007). Participants of the Internet-based survey (n=1537) were over 15 years of age from all over the country.

Results If all potentially fortifiable foods were to be fortified with calcium, the proportion of participants with calcium intake below the recommended level (< 800 mg day(-1)) would decrease from 20.3% to 3.0% in men and from 27.8% to 5.6% in women compared with the situation where no foods were fortified. At the same time, the proportion of participants with calcium intake above the tolerable upper intake level (UL, > 2500 mg day(-1)) would increase from 0.6% to 12.7% in men and from 0.1% to 3.8% in women. However, in a probability-based model (11% of all fortifiable foods to be fortified with calcium) the proportion of participants with calcium intake below the recommended level would be 15.7% in men and 23.2% in women. The proportion with intake above the UL in this model would be 1.2% in men and 0.7% in women.

Conclusions Food fortification would be a relatively effective and safe way to increase the calcium intake of the Finnish adult population.

Prospective study of risk factors for attempted suicide among patients with bipolar disorder

Isometsä, E., Valtonen, H., Suominen, K., Mantere, O., Leppämäki, S. and Arvilommi, P.

Psychiatr Danub. 2006; 18 Suppl 1: 46.

There are few prospective studies on risk factors for attempted suicide among representative samples of psychiatric patients with bipolar disorders.

Methods: In the Jorvi Bipolar Study (JoBS), 1630 psychiatric in- and outpatients of three Finnish cities were screened with the Mood Disorder Questionnaire (MDQ). Using SCID-I/P interviews, 191 patients were diagnosed with bipolar disorders (90 bipolar I, 101 bipolar II). Information on suicide attempts during the follow-up was obtained for 176 patients (92%) at the six-month and for 161 patients (84%) at the 18-month follow-up.

Results: During the 18-month follow-up 20% of patients (35/176) attempted suicide. In Cox regression model, baseline previous suicide attempts (OR 3.8, 95% c.l. 1.7 to 8.8; p=0.001), hopelessness (OR 1.2, 95% c.l. 1.1 to 1.3; p<0.001), depressive phase at index episode (OR 2.4, 95% c.l. 1.1 to 5.3; p=0.03) and younger age (OR 0.94, 95% c.l. 0.91 to 0.97; p< 0.001) were independent risk factors for suicide attempts.

Conclusions: During a medium-term follow-up as many as one fifth of psychiatric patients with bipolar disorder attempted suicide, which highlights the public health importance of suicidal behavior in bipolar disorder. Previous suicide attempts, hopelessness and depressive phase were the key indicators of risk.

ApoE polymorphism is associated with C-reactive protein in low-HDL family members and in normolipidemic subjects

Kahri, J., Soro-Paavonen, A., Ehnholm, C. and Taskinen, M. R.

Mediators of Inflammation. 2006. Article. IF 0.953

The study was aimed to compare inflammatory parameters between carriers of apoE4 isoforms (apoE4/3, apoE4/2, and apoE4/4 phenotypes) and those of carrying apoE3 isoform without apoE4 isoform (apoE3/3 phenotypes and apoE2/3 phenotypes).

The concentrations of serum hsCRP, sVCAM-1, sICAM-1, and sE-selectin were measured in 211 subjects from Finnish low-HDL families and in 157 normolipidemic subjects. The subjects with apoE4 isoform had lower concentrations of serum hsCRP both in low-HDL family members ( p < 0.05) and in normolipidemic subjects ( p < 0.01). The differences in serum CRP values remained significant after adjustment for age, BMI, smoking status, hypertension, gender, lipoprotein variables, and family number.

We conclude that apoE phenotype has a strong influence on serum CRP values.

Searching for genes affecting preferences for sweet foods; a Finnish family study

Keskitalo, K., Knaapila, A., Kallela, M., Palotie, A., Wessman, M., Peltonen, L., Tuorila, H. and Perola, M.

Chemical Senses. 2006; 31(5): A44-A44. Meeting Abstract. IF 2.506

Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study

Kivipelto, M., Ngandu, T., Laatikainen, T., Winblad, B., Soininen, H. and Tuomilehto, J.

Lancet Neurology. 2006; 5(9): 735-741. Article. IF 12.167

Background Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles.

Methods Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of beta coefficients and the dementia risk score was the sum of these individual scores (range 0-15).

Findings Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (>= 47 years), low education (< 10 years), hypertension, hypercholesterolaemia, and obesity. The dementia risk score predicted dementia well (area under curve 0.77; 95% CI 0.71-0.83). The risk of dementia according to the categories of the dementia risk score was 1.0% for those with a score of 0-5, 1.9% for a score of 6-7, 4.2% for a score of 8-9, 7.4% for a score of 10-11, and 16.4% for a score of 12-15. When the cut-off of 9 points or more was applied the sensitivity was 0.77, the specificity was 0.63, and the negative predictive value was 0.98.

Interpretation The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.

Microbial communities, biomass, and activities in soils as affected by freeze thaw cycles

Koponen, H. T., Jaakkola, T., Keinänen-Toivola, M. M., Kaipainen, S., Tuomainen, J., Servomaa, K. and Martikainen, P. J.

Soil Biology & Biochemistry. 2006; 38(7): 1861-1871. Article. IF 2.414

Two Finnish agricultural soils (peat soil and loamy sand) were exposed to four freeze-thaw cycles (FTC), with a temperature change from -17.3 +/- 0.4 degrees C to +4.1 +/- 0.4 degrees C. Control cores from both soils were kept at constant temperature (+6.6 +/- 2.0 degrees C) without FTCs. Soil N2O and CO2 emissions were monitored during soil thawing, and the effects of FTCs on soil microbes were studied. N2O emissions were extremely low in peat soil, possibly due to low soil water content. Loamy sand had high N2O emission, with the highest emission after the second FTC.

Soil freeze-thaw increased anaerobic respiration in both soil types during the first 3-4 FTCs, and this increase was higher in the peat soil. The microbial community structure and biomass analysed with lipid biomarkers (phospholipid fatty acids, 3- and 2- hydroxy fatty acids) were not affected by freezing-thawing cycles, nor was soil microbial biomass carbon (MIB-C). Molecular analysis of the microbial community structure with temperature gradient gel electrophoresis (TGGE) also showed no changes due the FTCs.

These results show that freezing and thawing of boreal soils does not have a strong effect on microbial biomass or community structure. (c) 2006 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery

Koskenkari, J. K., Kaukoranta, P. K., Rimpiläinen, J., Vainionpää, V., Ohtonen, P. P., Surcel, H. M., Juvonen, T. and Ala-Kokko, T. I.

Acta Anaesthesiologica Scandinavica. 2006; 50(8): 962-969. Article. IF 1.837

Background: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery.

Methods: Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed.

Results: High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P = 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P = < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P = 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected.

Conclusions: High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.

Leukocyte filter enhances neutrophil activation during combined aortic valve and coronary artery bypass surgery

Koskenkari, J. K., Rimpiläinen, J., Öhman, H., Surcel, H. M., Vainionpää, V., Biancari, F., Ala-Kokko, T. and Juvonen, T.

Heart Surgery Forum. 2006; 9(4): E693-E699. Article. IF 0.833

Objective. Cardiopulmonary bypass-induced systemic inflammatory reaction involving the expression of neutrophil surface adhesion molecules is the main mechanism leading to myocardial ischemia-reperfusion injury as well as multiorgan dysfunction. Patients undergoing prolonged cardiopulmonary bypass are especially at risk in this regard.

The aim of this prospective, randomized study was to evaluate the impact of continuous leukocyte filtration on the perioperative expression of neutrophil adhesion molecules along with the markers of systemic inflammation during combined coronary artery revascularization and aortic valve surgery due to aortic stenosis.

Patient and Methods. Twenty patients scheduled for combined coronary artery revascularization and aortic valve surgery due to aortic stenosis were randomized to undergo cardiopulmonary bypass with or without a leukocyte filter (LeukoGuard LG6). The expression of neutrophil adhesion molecules and proinflammatory cytokine response were measured.

Results. The use of the leukocyte filter significantly increased neutrophil CD11b expression (P-g = .003) compared to the control group, which was followed by a faster rise in interleukin-6 levels 5 minutes (median, 125 versus 34 pg/mL) and 2 hours after cardiopulmonary bypass (median, 158 versus 92 pg/mL, P-txg < .001), respectively. No marked differences in terms of levels of CD11a, CD62L, cardiac troponin-I, or oxyhemodynamics were observed.

Conclusions. The observed increased neutrophil activation and enhanced inflammatory response do not support the use of continuous leukofiltration in patients undergoing prolonged cardiopulmonary bypass.

Absence of endogenous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells

Lee-Rueckert, M., Vikstedt, R., Metso, J., Ehnholm, C., Kovanen, P. T. and Jauhiainen, M.

Journal of Lipid Research. 2006; 47(8): 1725-1732. Article. IF 3.909

In vitro experiments have demonstrated that exogenous phospholipid transfer protein (PLTP), i.e. purified PLTP added to macrophage cultures, influences ABCA1-mediated cholesterol efflux from macrophages to HDL. To investigate whether PLTP produced by the macrophages (i.e., endogenous PLTP) is also part of this process, we used peritoneal macrophages derived from PLTP-knockout (KO) and wild-type (WT) mice.

The macrophages were transformed to foam cells by cholesterol loading, and this resulted in the upregulation of ABCA1. Such macrophage foam cells from PLTP-KO mice released less cholesterol to lipid-free apolipoprotein A-I (apoA-I) and to HDL than did the corresponding WT foam cells. Also, when plasma from either WT or PLTP-KO mice was used as an acceptor, cholesterol efflux from PLTP-KO foam cells was less efficient than that from WT foam cells. After cAMP treatment, which upregulated the expression of ABCA1, cholesterol efflux from PLTP-KO foam cells to apoA-I increased markedly and reached a level similar to that observed in cAMP-treated WT foam cells, restoring the decreased cholesterol efflux associated with PLTP deficiency.

These results indicate that endogenous PLTP produced by macrophages contributes to the optimal function of the ABCAl-mediated cholesterol efflux-promoting machinery in these cells. Whether macrophage PLTP acts at the plasma membrane or intracellularly or shuttles between these compartments needs further study.

Enrolment of 22,000 adolescent women to cancer registry follow-up for long-term human papillomavirus vaccine efficacy: guarding against guessing

Lehtinen, M., Apter, D., Dubin, G., Kosunen, E., Isaksson, R., Korpivaara, E. L., Kyha-Österlund, L., Lunnas, T., Luostarinen, T., Niemi, L., Palmroth, J., Petäjä, T., Rekonen, S., Salmivesi, S., Siitari-Mattila, M., Svartsjö, S., Tuomivaara, L., Vilkki, M., Pukkala, E. and Paavonen, J.

International Journal of Std & Aids. 2006; 17(8): 517-521. Article. IF 1.211

Carcinoma, the second most common cancer among women. Vaccination of adolescents against HPV16/18 might prevent large proportion of cervical and other anogenital cancers. However, because of ethical reasons this cannot be proven by clinical studies.

To determine the long-term vaccine efficacy (VE) of HPV16/18 virus-like-particle (VLP) vaccine against cervical carcinoma in situ (CIS +) and invasive cervical carcinoma, the following three population-based cohorts of adolescent women have been enrolled: (1) women vaccinated with the HPV vaccine; (2) women vaccinated with hepatitis A control vaccine; and (3) unvaccinated control women.

These cohorts will be passively followed for cumulative incidence of CIS + endpoints by population-based cancer registry. Overall 24,046 16- to 17-year-old adolescent women from 18 cities in Finland were invited between May 2004 and June 2005 to participate in a phase III trial with bivalent HPV16/18 VLP vaccine. A total of 58,996 18- to 19-year-old women were invited in May 2005 to participate as unvaccinated controls. Women who reported their willingness to participate in an HPV vaccination trial had they been 1-2 years younger were eligible. Cumulative incidence (CI) of CIS + in our cohorts over 15 years is approximately 0.45%. VE of 70% against CIS+ with 80% power requires 3357-3189 HPV16/18 vaccine recipients, 3357-3189 other vaccine recipients, and 6714-9567 unvaccinated controls.

We have now enrolled 2404 HPV16/18 vaccine recipients, 2404 hepatitis A-vaccine recipients, and 5130 unvaccinated controls. This enrolment in addition to our earlier enrolment in another phase III trial guarantees enough power so that by 2020 we can ultimately provide data on the efficacy of HPV16/18 vaccination against CIS+.

Suicide attempters: a high vulnerability group or a group of suicides themselves?

Lönnqvist, J.

Psychiatr Danub. 2006; 18 Suppl 1: 34.

A nonfatal suicide attempt is the strongest known clinical predictor of eventual suicide. Suicides and attempted suicides are two overlapping populations that share common features, but are also distinguished by several factors. Suicide risk among suicide attempters is hundreds of times higher than in the general population. It is often estimated that about 10-15% of attempters eventually die by suicide. However, the risk is highest during the first months and years after the attempt and declines over time.

Long-term follow-up studies show that a history of a suicide attempt indicates suicide risk over the entire adult lifetime. The essential risk factor for suicide is a genuine intent to die. Most male and a substantial proportion of female suicides die in their first suicide attempt, a fact that necessitates early recognition of suicide risk, particularly among males. A suicide attempt indicates a severe risk of not only suicide but premature death in general. It appears that concentrating efficient treatment only on the most suicidal patients could prevent no more than two of five premature deaths.

More effort is therefore needed to prevent the excess mortality of suicide attempters by also addressing causes of death other than suicide.

Diabetes associated with a low serum uric acid level in a general Chinese population

Nan, H., Dong, Y., Gao, W., Tuomilehto, J. and Qiao, Q.

Diabetes Res Clin Pract. 2006. IF 1.236

OBJECTIVE: Serum uric acid (UA) is reported as an important marker of hypertension, coronary heart disease, and diabetes; diabetic subjects have low UA levels. The relationship between UA and fasting plasma glucose (FPG) and 2-h plasma glucose concentrations in non-diabetic subjects as well as in diabetic subjects in general population is not well known. This was investigated in a general Chinese population.

METHODS: A stratified, random cluster sampling method was performed to select a representative sample of general population aged 20-74 years in Qingdao in 2002. A total of 1288 men and 2344 women participated in the survey. The mean UA concentration was calculated for small glucose intervals and the trend was tested using general linear model.

RESULTS: The mean concentrations of UA were 381, 393, 371, and 345mumol/l in men with FPG of <6.1, 6.1-6.9, >/=7.0mmol/l (newly diagnosed diabetes), and in those with prior history of diabetes. They were 308, 322, 301, and 293mumol/l, respectively, in women. The UA levels declined with increasing FPG levels in individuals with newly diagnosed diabetes, with standardized coefficient of -0.26 in men and -0.20 in women, after multivariate adjustment for age, body mass index, triglycerides, and cardiovascular disease history. The relationship between 2-h glucose and UA was not as clear as that for FPG.

CONCLUSION: Serum UA levels tended to increase with increasing FPG levels in non-diabetic individuals, but decrease in diabetic individuals.

Validity of a food frequency questionnaire varied by age and body mass index

Paalanen, L., Männistö, S., Virtanen, M. J., Knekt, P., Räsänen, L., Montonen, J. and Pietinen, P.

Journal of Clinical Epidemiology. 2006; 59(9): 994-1001. Article. IF 2.538

Background and Objective: The validity of food frequency questionnaires (FFQs) in measuring food consumption and nutrient intake has to be assessed. The objective of this study was to assess the validity of a 128-item FFQ in specific subgroups of Finnish adults.

Methods: The study included 294 subjects (137 men and 157 women). A 3-day food record was used as the reference method.

Results: The mean intake of all nutrients except alcohol was higher measured with the FFQ than with the food records. In general, the Pearson correlations for energy adjusted nutrients between the FFQ and the food records were higher in women than in men. The correlations ranged from 0.14 (retinol) to 0.66 (fiber and alcohol) in men, and from 0.20 (long-chain n-3 fatty acids) to 0.70 (alcohol) in women. The results in subgroups showed that measuring nutrient intakes is more difficult among younger (30-50 years) women and overweight men and women than among others.

Conclusions: The study showed that the FFQ is a useful tool in epidemiologic studies in measuring the diet of Finnish adults given that the problems among specific subgroups are taken into account in interpretation. (c) 2006 Elsevier Inc. All fights reserved.

Determinants of functional disability and social adjustment in major depressive disorder: a prospective study

Rytsälä H. J., Melartin, T. K., Leskelä, U. S., Lestelä-Mielonen, P. S., Sokero, T. P. and Isometsä, E. T.

J Nerv Ment Dis. 2006; 194(8): 570-6. IF 1.738

We examined prospectively factors influencing social and occupational disability and social adjustment among patients with major depressive disorder.

The Vantaa Depression Study comprises a cohort of psychiatric inpatients and outpatients with major depressive disorder in the city of Vantaa, Finland. We prospectively interviewed 193 of 269 (72%) patients both 6 and 18 months after baseline. Axis I and II diagnoses were assessed via semistructured WHO Schedules for Clinical Assessment in Neuropsychiatry 2.0 and SCID-II interviews. Global disability and social and work adjustment were assessed. Patients' functional disability and social adjustment were alleviated concurrently with recovery from depression during the follow-up. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed.

Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support had significant influence.

Adequacy of, attitudes towards and adherence to treatments by depressed patients with or without suicidal behaviour

Sokero, P., Rytsälä, H., Melartin, T., Leskelä, U., Lestelä-Mielonen, P. and Isometsä, E.

Psychiatr Danub. 2006; 18 Suppl 1: 82.

Background: Suicidal patients with major depressive disorder (MDD) have been often found to be un- or undertreated. Their attitudes and adherence to treatments provided have been seldom investigated.

Method: In the Vantaa Depression Study, we compared MDD patients with no suicidal behaviour (NS, n=92), suicidal ideation (SI, n=92) or suicide attempts (SA, n=34) during the preceding index episode or at the baseline interview. We investigated differences in treatments received, self-reported attitudes and adherence to treatments during the following 6 months of their treatment.

Results: Due to their higher severity of depression, patients with SI or SA received antidepressants more often, more often received adequate antidepressant treatment, and had more frequent appointments with psychiatrists plus psychotherapeutic support from other professionals than the NS patients. The SI and SA patients had more favourable attitudes toward antidepressant treatment than the NS patients. This difference persisted even after adjusting for the confounding effect of severity of depression (HAM-D). Adherence to treatment did not to differ between groups during the follow-up.

Conclusions: Suicidal behaviour among psychiatric patients with MDD is not a factor that markedly influences treatments provided, neither is it associated with more negative attitudes towards, or adherence to treatment among psychiatric patients entering treatment.

Increased prostanoid dependency of arterial relaxation in Chlamydia pneumoniae-infected mice

Törmäkangas, L., Ketonen, J., Leinonen, M., Saikku, P. and Paakkari, I.

J Med Microbiol. 2006; 55(Pt 8): 1017-21. IF 2.318

Endothelial dysfunction plays an important role in the development of atherosclerosis. Previous studies have shown that inoculation with Chlamydia pneumoniae contributes to atherosclerotic development in rabbits and hypercholesterolaemic mice and causes endothelial dysfunction in apolipoprotein E-deficient mice. The effect of acute C. pneumoniae infection on endothelial function in normocholesterolaemic C57BL/6J mice was studied by measuring the force of contraction of the descending aorta after noradrenaline stimulation and in response to methacholine-induced relaxation. In addition, the effects of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the cyclooxygenase inhibitor diclofenac on relaxation were assessed. Pre-treatment of the aortas with L-NAME decreased the relaxation response in both the infected and uninfected groups and no significant difference was detected between these groups, whereas diclofenac significantly attenuated the relaxation response only in the infected animals.

In conclusion, infection shifted the balance of endothelium-derived relaxing factors from nitric oxide towards vasorelaxing prostanoids in C57BL/6J mice.