29.10.2007

Gunnar, T., Engblom, C. and Ariniemi, K.

Journal of Chromatography A. 2007; 1166(1-2): 171-180. Article. IF 3.554

Innovative features and technical improvements in modem bench-top quadrupole gas chromatograph-mass spectrometer (GC-MS) have prepared the way for faster and more cost-effective applications while still maintaining sufficient chromatographic resolution, speed of MS data acquisition and reliability of analytical methodology. In this paper, a short wide-bore capillary column with low film thickness (5 m x 0.32 mm i.d., 0.1 mu m) was used a pre-fractionating column and only chosen heart-cuts were transferred to the second chromatographic dimension (15 m x 0.25 mm i.d., 0.25 mu m) by means of a pressure-adjusted continual flow type switching device for quantification of five common amphetamine-type stimulant drugs. The instrumental setting used, in combination with carefully optimized operational fast GC and MS parameters, markedly decreased the retention times of the targeted analytes, e.g., amphetamine 0.891 min and methamphetamine 1.037 min, and the total chromatographic runtime (1.700 min), as well as reducing the need for continuous cleaning of the MS ion source and increasing column life compared with conventional GC-MS approaches. The performance of the instrumental configuration and analytical method was evaluated in validation experiments and the method was also applied to authentic samples. The method demonstrates the potential of fast GC-MS in combination with a gas-phase microfluidic Deans switch device for analysing of (semi)volatile compounds, such as amphetamine-type stimulant (ATS) drugs. This should be particularly useful in modem laboratories aiming at cost-efficient analysis as well as the optimum use of available laboratory capacity and instrumentation. (c) 2007 Elsevier B.V. All rights reserved.

Voxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment

Hamalainen, A., Tervo, S., Grau-Olivares, M., Niskanen, E., Pennanen, C., Huuskonen, J., Kivipelto, M., Haenninen, T., Tapiola, M., Vanhanen, M., Hallikainen, M., Helkala, E. L., Nissinen, A., Vanninen, R. and Soininen, H.

Neuroimage. 2007; 37(4): 1122-1131. Article. IF 5.559

Recent research has shown an increased rate of conversion to dementia in subjects with mild cognitive impairment (MCI) compared to controls. However, there are no specific methods to predict who will later develop dementia.

In the present study, 22 controls and 56 MCI subjects were followed on average for 37 months (max. 60 months) and studied with magnetic resonance imaging (MRI) at baseline to assess changes in brain structure associated to later progression to dementia. Voxel-based morphometry (VBM) was used to investigate gray matter atrophy.

During the follow-up, 13 subjects progressed to dementia. At baseline, no differences were detected in age or education between the control and MCI subjects, but they differed by several neuropsychological tests. The stable and progressive MCI subjects differed only by CDR sum of boxes scores and delayed verbal recall, which were also significant predictors of conversion to dementia. At the baseline imaging, the MCI subjects showed reduced gray matter density in medial temporal, temporoparietal as well as in frontal cortical areas compared to controls. Interestingly, the progressive MCI subjects showed atrophy in the left temporoparietal and posterior cingulate cortices and in the precuneus bilaterally, and a trend for hippocampal atrophy when compared to the stable MCI subjects.

We conclude that widespread cortical atrophy is present already two and a half years before a clinical diagnosis of dementia can be set. (c) 2007 Elsevier Inc. All rights reserved.

A cluster of Candida krusei infections in a haematological unit

Hautala, T., Ikaheimo, I., Husu, H., Saily, M., Siitonen, T., Koistinen, P., Vuopio-Varkila, J., Koskela, M. and Kujala, P.

Bmc Infectious Diseases. 2007; 7. Article. IF 1.898

Background: Candida krusei infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of C. krusei in a haematological unit which had experienced an unusually high incidence of cases.

Methods: We searched for C. krusei contamination of the hospital environment and determined the level of colonization in patients and health care workers. We also analyzed the possible association between exposure to prophylactic antifungals or chemotherapeutic agents and occurrence of C. krusei. The C. krusei isolates found were genotyped by pulsed-field electrophoresis method in order to determine possible relatedness of the cases.

Results: Twelve patients with invasive C. krusei infection and ten patients with potentially significant infection or mucosal colonization were documented within nine months. We were unable to identify any exogenic source of infection or colonization. Genetic analysis of the isolates showed little evidence of clonal transmission of C. krusei strains between the patients. Instead, each patient was colonized or infected by several different closely related genotypes. No association between medications and occurrence of C. krusei was found.

Conclusion: Little evidence of nosocomial spread of a single C. krusei clone was found. The outbreak may have been controlled by cessation of prophylactic antifungals and by intensifying infection control measures, e. g. hand hygiene and cohorting of the patients, although no clear association with these factors was demonstrated.

VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation

Jalkanen, S. and Salmi, M.

Arterioscler Thromb Vasc Biol. 2007. IF 6.883

Leukocyte extravasation from the blood into tissues is crucial for normal immune surveillance and in inflammation. Traditionally molecules belonging to selectin, chemokine, integrin, and immunoglobulin super families are thought to mediate the multiple adhesive and activation events needed for a successful emigration cascade. Recently, emerging evidence suggests that enzymes expressed on the surface of endothelial cells and leukocytes also contribute to the leukocyte extravasation cascade. Here we briefly review the role of vascular adhesion protein- 1 (VAP-1) and CD73, 2 cell surface enzymes, in leukocyte migration form the blood into the tissues. Importantly, specific enzyme inhibitors, gene-deficient mice, and recombinant enzymes have recently unambiguously shown that the catalytic activity of these enzymes regulates the leukocyte traffic. The concept of enzymatic regulation of leukocyte extravasation provides new insight into the multi-step adhesion cascade and opens new possibilities for inhibiting inappropriate inflammatory reaction through the use of small molecule enzyme inhibitors.

Nationwide trends in molecular epidemiology of methicillin-resistant Staphylococcus aureus, Finland, 1997-2004

Kerttula, A. M., Lyytikainen, O., Karden-Lilja, M., Ibrahem, S., Salmenlinna, S., Virolainen, A. and Vuopio-Varkila, J.

Bmc Infectious Diseases. 2007; 7. Article. IF 1.898

Background: In Finland, the annual number of MRSA notifications to the National Infectious Disease Register ( NIDR) has constantly increased since 1995, and molecular typing has revealed numerous outbreak isolates of MRSA. We analyzed the data on MRSA notifications of the NIDR, and MRSA isolates were identified mainly by pulsed-field gel electrophoresis ( PFGE) at the National Reference Laboratory ( NRL) in Finland during 1997-2004. One isolate representative of each major PFGE type was further characterized by multilocus sequence ( MLST)-, staphylococcal cassette chromosome mec ( SCCmec)-, and Panton-Valentine leukocidin ( PVL)- typing.

Results: The annual number of MRSA notifications to the NIDR rose over ten-fold, from 120 in 1997 to 1458 in 2004, and the proportion of MRSA among S. aureus blood isolates tripled, from < 1% during 1997 - 2003 to 2.8% in 2004. During the same period of time, 253 different strains among 4091 MRSA isolates were identified by PFGE: 215 were sporadic and 38 outbreak/epidemic strains, including 24 new strains. Two epidemic strains resembling internationally recognized MRSA clones accounted for most of the increase: FIN-16 ( ST125: 1A) from < 1% in 1997 to 25% in 2004, and FIN-21 ( ST228:1) from 6% in 2002 to 28% in 2004. Half of the ten most common strains carried SCCmec IV or V.

Conclusion: The predominant MRSA strains seem to change over time, which encourages us to continue implementing active control measures with each new MRSA case.

Reproductive history and carotid intima-media thickness

Kharazmi, E., Moilanen, L., Fallah, M., Kaaja, R., Kattainen, A., Kahonen, M., Jula, A., Kesaniemi, A. and Luoto, R.

Acta Obstetricia Et Gynecologica Scandinavica. 2007; 86(8): 995-1002. Article. IF 1.327

Background. Intima-media thickness (IMT) of the carotid arteries is a valid measure of preclinical atherosclerosis which may predict cardiovascular outcomes. Metabolic and hormonal changes associated with the reproductive history of women may contribute to the development of cardiovascular disease (CVD).

Methods. In a population-based cross-sectional study comprising 746 Finnish women, aged 45-74 years, associations of reproductive history ( assessed by questionnaire) and measures of subclinical atherosclerosis ( by ultrasonographic detection) were studied. Statistical methods included linear and logistic regression models.

Results. Mean carotid IMT was positively associated with parity, but after adjustment for age its statistical significance disappeared. Women with a history of stillbirth tended to have higher IMT than other women. History of hysterectomy was an independent determinant of carotid plaque in models with age, blood pressure, fasting blood glucose and cholesterol, body mass index (BMI), education and smoking (odds ratio (OR): 0.32; 95% confidence interval (CI): 0.11-0.96). But when oophorectomy (yes/no) was included in the model, this association lost its statistical significance (adjusted OR: 0.36; 95% CI: 0.11-1.22). A history of stillbirth was associated with an increased age-adjusted risk of plaque (OR = 3.43; 95% CI: 1.07-11.05), but in the fully adjusted model it lost its statistical significance (OR = 3.61; 95% CI: 0.86-15.23).

Conclusion. Stillbirth was associated with increased risk of atherosclerotic plaque. Atherosclerosis is a lifelong process to which stillbirth is related. However, due to the cross-sectional design of this study, the causality of this association remains unclear.

Carotid intima-media thickness and cognitive function in elderly women: A population-based study

Komulainen, P., Kivipelto, M., Lakka, T. A., Hassinen, M., Helkala, E. L., Patja, K., Nissinen, A. and Rauramaa, R.

Neuroepidemiology. 2007; 28(4): 207-213. Article. IF 2.352

Objective: Several vascular risk factors have been linked to cognitive decline. However, little is known about the association between the atherosclerotic process and cognitive impairment. We investigated whether carotid intima-media thickness (IMT) predicts the risk of cognitive impairment and whether the putative impairment is specific for some cognitive domains.

Methods: A 12-year population-based followup study was performed for a total of 91 women, aged 60-70 years at baseline. Ultrasonographically assessed carotid artery IMT and the Mini-Mental State Examination test were performed at baseline and 12-year follow-up. A detailed cognitive evaluation for memory and cognitive speed was performed in 2003. The mean of left and right carotid bifurcation IMT was used in the analyses for association with the risk for poor cognitive speed and memory.

Results: Increased IMT at baseline was an independent predictor for poor memory (beta = -5.004, 95% confidence interval = -7.74 to -2.27; p = 0.001) and cognitive speed ( beta = 2.562, 95% confidence interval = 1.19-4.94; p = 0.035) at 12-year follow-up after adjustment for age, education, depression, plasma LDL cholesterol, systolic blood pressure, cardiovascular disease, hormone replacement therapy, smoking, alcohol consumption and physical activity. The risk for poor memory ( p = 0.023 for linear trend) and cognitive speed ( p = 0.070 for linear trend) increased with increasing IMT tertiles.

Conclusions: Carotid IMT predicts an increased risk for cognitive impairment, particularly poor memory and cognitive speed, in elderly women. Copyright (c) 2007 S. Karger AG, Basel

Gene expression profiling during differentiation of human monocytes to macrophages or dendritic cells

Lehtonen, A., Ahlfors, H., Veckman, V., Miettinen, M., Lahesmaa, R. and Julkunen, I.

J Leukoc Biol. 2007; 82(3): 710-20. IF 4.572

Macrophages and dendritic cells (DC) are APC, which regulate innate and adaptive immune responses. Macrophages function locally mainly, maintaining inflammatory responses in tissues, whereas DC take up microbes, mature, and migrate to local lymph nodes to present microbial antigens to naive T cells to elicit microbe-specific immune responses. Blood monocytes can be differentiated in vitro to macrophages or DC by GM-CSF or GM-CSF + IL-4, respectively. In the present study, we performed global gene expression analyses using Affymetrix HG-U133A Gene Chip oligonucleotide arrays during macrophage and DC differentiation. During the differentiation process, 340 and 350 genes were up-regulated, and 190 and 240 genes were down-regulated in macrophages and DC, respectively. There were also more that 200 genes, which were expressed differentially in fully differentiated macrophages and DC. Macrophage-specific genes include, e.g., CD14, CD163, C5R1, and FcgammaR1A, and several cell surface adhesion molecules, cytokine receptors, WNT5A and its receptor of the Frizzled family FZD2, fibronectin, and FcepsilonR1A were identified as DC-specific.

Our results reveal significant differences in gene expression profiles between macrophages and DC, and these differences can partially explain the functional differences between these two important cell types.

Recommended and prescribed symptomatic treatment for acute maxillary sinusitis in Finnish primary care

Pulkki, J., Rautakorpi, U. M., Huikko, S., Honkanen, P., Klaukkas, T., Makela, M., Palva, E., Roine, R., Sarkkinen, H., Huovinen, P. and Varonen, H.

Rhinology. 2007; 45(3): 197-201. IF 1.096

We studied the use of symptomatic medication in the treatment of acute maxillary sinusitis (AMS) in primary care and whether this use is in accordance with national guidelines. The data was collected annually in the Antimicrobial Treatment Strategies (MIKSTRA) Program in 30 primary health care centres throughout Finland during one week in November in the years from 1998 to 2002. Physicians and nurses collected the data about the diagnoses, prescription-only medicines and over the counter medicines prescribed or recommended for all patients with an infection during the study weeks. The MIKSTRA data comprised of 23.002 first consultations for an infection: 2.448 patients were diagnosed as having AMS. Altogether, 41% of them received some symptomatic medicine. Antihistamines with or without sympathomimetics were the most commonly prescribed or recommended symptomatic medicines (23% of the patients). For comparison, systemic antibacterial agents were prescribed for 93% of the AMS patients. We conclude that Finnish physicians recommend or prescribe more symptomatic medication without proven efficacy for AMS than recommended by the national guidelines. Especially, the use of antihistamines with or without sympathomimetics, mostly the combination of acrivastine and pseudoephedrine, was common although antihistamines were recommended only for patients with allergy or nasal polyps.

Prevention of type 2 diabetes - Lessons we have learnt for implementation

Schwarz, P. E. H. and Peltonen, M.

Hormone and Metabolic Research. 2007; 39(9): 636-641. Review. IF 1.997

The challenge today is to implement successful diabetes prevention programs in general health care. Even if not all questions for the prevention of diabetes are answered, we have today overwhelming evidence that diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This information has to be translated now into well-defined strategies for screening and treating high risk population in daily practice. It is necessary then to develop and implement prevention programs into clinical practice considering scientific aspects and practical requirements during implementation. While translating the scientific evidence into population based intervention strategies more and more questions arise, mostly related to economic and structural requirements during implementation. At the end, giving the right answers to these questions will decide about the success of implemented prevention strategies. Here, we will try to answer some of the questions which arose during the implementation of a prevention management concept into clinical practice. We focus on the development of a structured prevention management program which will enable implementation of diabetes prevention into clinical practice.

A common variant of HMGA2 is associated with adult and childhood height in the general population

Weedon, M. N., Lettre, G., Freathy, R. M., Lindgren, C. M., Voight, B. F., Perry, J. R. B., Elliott, K. S., Hackett, R., Guiducci, C., Shields, B., Zeggini, E., Lango, H., Lyssenko, V., Timpson, N. J., Burtt, N. P., Rayner, N. W., Saxena, R., Ardlie, K., Tobias, J. H., Ness, A. R., Ring, S. M., Palmer, C. N. A., Morris, A. D., Peltonen, L., Salomaa, V., Smith, G. D., Groop, L. C., Hattersley, A. T., McCarthy, M. I., Hirschhorn, J. N. and Frayling, T. M.

Nature Genetics. 2007; 39(10): 1245-1250. Article. IF 24.176

Human height is a classic, highly heritable quantitative trait.

To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6), N=3,207). We estimate that rs1042725 explains similar to 0.3% of population variation in height (similar to 0.4 cm increased adult height per C allele).

There are few examples of common genetic variants reproducibly associated with human quantitative traits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.