21.1.2008

De Bruin, Y. B., Hakkinen, P., Lahaniatis, M., Papameletiou, D., Del Pozo, C., Reina, V., Van Engelen, J., Heinemeyer, G., Viso, A. C., Rodriguez, C. and Jantunen, M.

Journal of Exposure Science and Environmental Epidemiology. 2007; 17: S55-S66. Article. IF 2.492

This paper analyzes the way risk management measures (RMMs) for consumer products have been used to date in authority and industry risk assessments.

A working concept for consumer product RMMs is developed, aimed at controlling, limiting or avoiding exposures, and helping to insure the safe use (or handling) of a substance as part of a consumer product. Particular focus is placed on new requirements introduced by REACH (registration, evaluation, and authorization of chemicals). A RMMs categorization approach is also developed, dividing consumer product RMMs into those that are product integrated and those that are communicated to consumers. For each of these categories, RMMs for normal use, accidental use or misuse need to be distinguished. The level of detail for documenting, assessing and communicating RMMs across supply chains can vary, depending on the type of the assessment ( tiered approach).

Information on RMMs was collected from published sources to demonstrate that a taxonomical approach using standard descriptors for RMMs libraries is needed for effective information exchange across supply chains.

Measurement of acetaldehyde: what levels occur naturally and in response to alcohol?

Eriksson, C. J.

Novartis Found Symp. 2007; 285: 247-55; discussion 256-60.

The aim of the present paper is to update the status regarding human acetaldehyde levels in blood, breath and saliva during normal ethanol oxidation, i.e. without deficiency in, or inhibition of, aldehyde dehydrogenase activity.

The previous conclusion according to which no detectable (<0.5 microM), adequately determined 'free and/or loosely bound' acetaldehyde has not yet been found in venous blood, more or less, still holds. The only new findings within this context consist of low venous blood acetaldehyde levels (1-3 microM on average) observed in some women during the use of oral contraceptives or during the high oestradiol phases of normal menstrual cycle. Breath acetaldehyde levels are about 10-20 and 20-40nM at blood ethanol concentrations of about 10 and 20mM, respectively. Theoretically calculated corresponding blood acetaldehyde levels in pulmonary blood would be about 2-4 and 4-8 microM.

The acetaldehyde in the breath most likely reflects pulmonary blood acetaldehyde, microbial and tissue acetaldehyde production in the aerodigestive tract. As well as with breath acetaldehyde, salivary acetaldehyde levels also correlate positively with the blood ethanol concentrations. At blood ethanol concentrations of about 10 and 20 mM the average acetaldehyde concentration in saliva is about 15-25 and 20-40 microM, respectively. Saliva acetaldehyde represents mostly microbial acetaldehyde formation in the oral cavity, but also, to some extent, ethanol oxidation in nearby tissues. More studies are still needed to clarify the proportion of the underlying sources for blood, breath and salivary acetaldehyde at different ethanol concentrations.

The problem with rapid acetaldehyde oxidation, which may markedly affect the recovery of low acetaldehyde levels, also needs to be solved.

The role of genes in growth and later health

Eriksson, J. G.

Nestle Nutr Workshop Ser Pediatr Program. 2008; 61: 69-77.

Genetic factors are of importance for the development of the metabolic syndrome and type 2 diabetes, but despite extensive research the identification of the underlying genes has not been fruitful.

This report focuses on the interactions between intrauterine growth and genes in relation to adult health outcomes based upon findings from the Helsinki Birth Cohort Study.

Candidate genes for type 2 diabetes and the metabolic syndrome have been focused upon and we report on interactions between polymorphisms of the peroxisome proliferator-activated receptor (PPAR)gamma-2, plasma cell glycoprotein (PC-1) and the glucocorticoid receptor (GR) genes and - prenatal growth in relation to adult health outcomes. In elderly individuals the effects of the Pro12Pro/Pro12Ala polymorphisms of the PPARgamma-2 gene depend on their body size at birth. Individuals, who had a small body size at birth and were carriers of the Ala allele, seem to be protected against insulin resistance and type 2 diabetes in later life. Similar gene environment interactions will be described in relation to the PC-1 and the GR genes.

We propose that these findings reflect gene-early environment interactions and can be attributed to the phenomenon of developmental plasticity.

Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease

Hu, G., Jousilahti, P. and Tuomilehto, J.

European Heart Journal. 2007; 28(24): 3059-3066. Article. IF 7.286

Aims To evaluate the joint associations of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the incidence of coronary heart disease (CHD) and CHD mortality.

Methods and results Study cohorts included 49 775 Finnish subjects aged 25-74 without history of CHD and stroke. The multivariable-adjusted hazard ratios (HRs) of CHD incidence were 1.25, 1.69, 1.25, 1.83, 1.85, 2.39, 2.15, and 3.31 (P-value for trend < 0.001), respectively, among men with hypertension I (blood pressure 140-159/90-94 mmHg or using antihypertensive drugs at baseline but blood pressure < 160/95 mmHg) only, with hypertension II ( blood pressure >= 160/ 95 mmHg) only, with incident diabetes during follow-up only, with both hypertension I and incident diabetes, with both hypertension II and incident diabetes, with history of diabetes at baseline only, with both hypertension I and history of diabetes, and with both hypertension II and history of diabetes compared with men without either of these diseases. The corresponding HRs of CHD incidence among women were 1.52, 2.37, 2.45, 3.78, 4.56, 5.63, 6.10, and 7.41 (P-value for trend,0.001), respectively. The impact on CHD mortality associated with the different strata of hypertension and diabetes was almost the same or a little stronger compared with that on the CHD incidence.

Conclusion Hypertension and type 2 diabetes increase the CHD risk independently, and their combination increases the risk dramatically, particularly in women.

Source apportionment of population representative samples of PM(2.5) in three European cities using structural equation modelling

Ilacqua, V., Hanninen, O., Saarela, K., Katsouyanni, K., Kunzli, N. and Jantunen, M.

Sci Total Environ. 2007; 384(1-3): 77-92. IF 2.359

Apportionment of urban particulate matter (PM) to sources is central for air quality management and efficient reduction of the substantial public health risks associated with fine particles (PM(2.5)). Traffic is an important source combustion particles, but also a significant source of resuspended particles that chemically resemble Earth's crust and that are not affected by development of cleaner motor technologies. A substantial fraction of urban ambient PM originates from long-range transport outside the immediate urban environment including secondary particles formed from gaseous emissions of mainly sulphur, nitrogen oxides and ammonia. Most source apportionment studies are based on small number of fixed monitoring sites and capture well population exposures to regional and long-range transported particles. However, concentrations from local sources are very unevenly distributed and the results from such studies are therefore poorly representative of the actual exposures.

The current study uses PM(2.5) data observed at population based random sampled residential locations in Athens, Basle and Helsinki with 17 elemental constituents, selected VOCs (xylenes, trimethylbenzenes, nonane and benzene) and light absorbance (black smoke). The major sources identified across the three cities included crustal, salt, long-range transported inorganic and traffic sources. Traffic was associated separately with source categories with crustal (especially Athens and Helsinki) and long-range transported chemical composition (all cities).

Remarkably high fractions of the variability of elemental (R(2)>0.6 except for Ca in Basle 0.38) and chemical concentrations (R(2)>0.5 except benzene in Basle 0.22 and nonane in Athens 0.39) are explained by the source factors of an SEM model. The RAINS model that is currently used as the main tool in developing European air quality management policies seems to capture the local urban fraction (the city delta term) quite well, but underestimates crustal particle levels in the three cities of the current study.

Utilizing structural equation modelling parallel with traditional principal component analysis (PCA) provides an objective method to determine the number of factors to be retained in a model and allows for formal hypotheses testing.

Alexithymia, depression and sleep disturbance symptoms

Kronholm, E., Partonen, T., Salminen, J. K., Mattila, A. K. and Joukamaa, M.

Psychotherapy and Psychosomatics. 2008; 77(1): 63-65. Letter. IF 4.333

The effects of lifestyle intervention for hypertension on low back pain - A randomized controlled trial

Mattila, R., Malmivaara, A., Kastarinen, M., Kivelä, S. L. and Nissinen, A.

Spine. 2007; 32(26): 2943-2947. Article. IF 2.351

Study Design, Randomized controlled trial.

Objective. To assess the effects of a lifestyle intervention for hypertension on low back pain.

Summary of Background Data. According to prospective etiologic studies, a causal association exists between certain lifestyle factors and low back pain. These factors are similar to those that elevate the risk for hypertension. Nevertheless, no randomized controlled trial has assessed effectiveness of lifestyle intervention for the treatment of hypertension on the prevalence of low back pain.

Methods. A total of 731 hypertensive employees from 45 worksites were assigned to multidisciplinary lifestyle interventions for hypertension in a rehabilitation center or to routine care in occupational or primary healthcare services during 12 months. Questionnaire data on low back pain were used to assess the effects of the intervention on the extent of low back pain and disability.

Results. The changes in prevalence and duration of low back pain, and related disability did not differ between the 2 groups, although there were favorable changes in some risk factors, such as body weight and physical inactivity. Subgroup analyses among patients with moderately heavy or heavy work showed that the prevalence of low back pain during the previous 12 months decreased more in the intervention than in the control group.

Conclusion. Multidisciplinary lifestyle intervention aimed to reduce hypertension is not effective at reducing prevalence of low back pain or disability. However, in the subgroup of persons doing moderate or heavy work, the intervention seemed to reduce prevalence of low back pain during the 1-year follow-up.

Depression and its association with diabetes, cardiovascular disease, and birth weight

Paile-Hyvarinen, M., Raikkonen, K., Forsen, T., Kajantie, E., Yliharsila, H., Salonen, M. K., Osmond, C. and Eriksson, J. G.

Annals of Medicine. 2007; 39(8): 634-640. Article. IF 4.594

Background. Diabetes increases the risk for depression.

Aim. To study the independent effects of diabetes mellitus (DM) and cardiovascular disease (CVD) on the prevalence of depression and to examine low birth weight as a possible common explanatory factor.

Methods. 2003 subjects from the Helsinki Birth Cohort Study underwent a 75-g oral glucose tolerance test and filled out the Beck Depression Inventory.

Results. Depressive symptoms were more prevalent among subjects with diabetes (23.5%) than among those with normal glucose tolerance (16.6%) (P < 0.001). A history of CVD also markedly increased the odds of having depressive symptoms (odds ratio (OR) =2.38, 95% confidence interval (CI) = 1.70-3.32, P < 0.001). The association between DM and depressive symptoms was, however, rendered non-significant when adjusting for the presence of CVD. Being born with a low birth weight doubled the risk for having depressive symptoms (OR=2.64, 95% CI=1.42-4.91, P=0.002) and magnified the association between CVD/DM and depression.

Conclusion. Diabetes has only a minor independent effect on concurrent occurrence of depressive symptoms, while cardiovascular disease seems to be a more important underlying factor. The association between disease and depression is in particular characteristic to individuals born with a low birth weight.

Hepatitis C virus proteins interfere with the activation of chemokine gene promoters and downregulate chemokine gene expression

Sillanpää, M., Kaukinen, P., Melen, K. and Julkunen, I.

J Gen Virol. 2008; 89(Pt 2): 432-43. IF 3.110

The hepatitis C virus (HCV) non-structural (NS) 3/4A protein complex inhibits the retinoic acid inducible gene I (RIG-I) pathway by proteolytically cleaving mitochondria-associated CARD-containing adaptor protein Cardif, and this leads to reduced production of beta interferon (IFN-beta).

This study examined the expression of CCL5 (regulated upon activation, normal T-cell expressed and secreted, or RANTES), CXCL8 (interleukin 8) and CXCL10 (IFN-gamma-activated protein 10, or IP-10) chemokine genes in osteosarcoma cell lines that inducibly expressed NS3/4A, NS4B, core-E1-E2-p7 and the entire HCV polyprotein. Sendai virus (SeV)-induced production of IFN-beta, CCL5, CXCL8 and CXCL10 was downregulated by the NS3/4A protein complex and by the full-length HCV polyprotein. Expression of NS3/4A and the HCV polyprotein reduced the binding of interferon regulatory factors (IRFs) 1 and 3 and, to a lesser extent, nuclear factor (NF)-kappaB (p65/p50) to their respective binding elements on the CXCL10 promoter during SeV infection. Furthermore, binding of IRF1 and IRF3 to the interferon-stimulated response element-like element, and of c-Jun and phosphorylated c-Jun to the activator protein 1 element of the CXCL8 promoter, was reduced when NS3/4A and the HCV polyprotein were expressed. In cell lines expressing NS3/4A and the HCV polyprotein, the subcellular localization of mitochondria was changed, and this was kinetically associated with the partial degradation of endogenous Cardif.

These results indicate that NS3/4A alone or as part of the HCV polyprotein disturbs the expression of IRF1- and IRF3-regulated genes, as well as affecting mitogen-activated protein kinase kinase- and NF-kappaB-regulated genes.

Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study

Vasankari, T., Holmstrom, P., Ollgren, J., Liippo, K., Kokki, M. and Ruutu, P.

BMC Public Health. 2007; 7: 291. IF 1.603

BACKGROUND: We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes.

METHODS: Medical records of all cases in 1995 - 1996 were abstracted to assess outcome of treatment. Outcome was divided into three groups: favourable, death and other unfavourable. Predictors of unfavourable outcome were assessed in univariate and multivariate analysis.

RESULTS: Among 629 cases a favourable outcome was achieved in 441 (70.1%), 17.2% (108) died and other unfavourable outcome took place in 12.7% (80). Significant independent risk factors for death were male sex, high age, non-HIV -related immunosuppression and any other than a pulmonary specialty being responsible for stopping treatment. History of previous tuberculosis was inversely associated with the risk of death. For other unfavourable treatment outcomes, significant risk factors were pause(s) in treatment, treatment with INH+RIF+EMB/SM, and internal medicine specialty being responsible at the end of the treatment.

CONCLUSION: We observed a significant association with unfavourable outcome for the specialty responsible for treatment being other than pulmonary, but not for the volume of cases, which has implications for system arrangements. Poor outcomes associated with immunosuppression and advanced age, with frequent comorbidity, stress a low threshold of suspicion, availability of rapid diagnostics, and early empiric treatment as probable approaches in attempting to improve treatment outcomes in countries with very low incidence of TB.

Visual impairment in persons with psychotic disorder

Viertio, S., Laitinen, A., Perälä, J., Saarni, S. I., Koskinen, S., Lönnqvist, J. and Suvisaari, J.

Social Psychiatry and Psychiatric Epidemiology. 2007; 42(11): 902-908. Article.

Background Persons with psychotic disorder may have poorer visual acuity (VA).

The aim of the study is to investigate in a general population the prevalence of impaired habitual VA and self-reported difficulties in vision among persons with different psychotic disorders.

Method A nationally representative sample of 6,663 persons aged 30 or older whose binocular VA for distance and for near vision was measured with current spectacles, if any. Diagnostic assessment of DSM-IV psychotic disorders used both SCID interview and case note data. Life-time ever diagnoses of psychotic disorders were classified into schizophrenia, other non-affective psychotic disorders and affective psychoses.

Results After adjusting for age and sex, schizophrenia was associated with significantly increased odds of having visual impairment for distance (OR 5.04, P < 0.0001) and for near vision (OR 6.22, P < 0.0001), while other psychotic disorders were not. Self-reported problems in VA were more common in persons with schizophrenia and other non-affective psychotic disorders than in the remaining study sample. Only 43.9% of persons with schizophrenia, compared with 69.7% in the total sample (chi(2) = 13.79, d.f. 1, P = 0.0002), had had their vision examined during the 5 years before the VA measurement.

Conclusions Because persons with schizophrenia attend vision examinations substantially less frequently than others, and their vision is notably weaker, regular ocular evaluations should be included in physical health monitoring in psychotic disorders.