Soolevähi laboratoorsete sõeluuringute võimalused

2007. aastal sotsiaalministri kinnitatud riiklik vähistrateegia aastateks 2007–2015 hõlmab kõiki vähitõrje valdkondi: ennetamist, varajast avastamist, sõeluuringuid, ravi ja teadusuuringuid. Strateegia eesmärgiks on saavutada rahvastiku haigestumise ja suremuse püsiv vähenemine pahaloomulistesse kasvajatesse (1). Eestis on käivitunud emakakaelavähi ja rinnavähi sõel uuringute süstemaatilised programmid (2). Selle aasta aprilli lõpus Tal l innas toimunud erialadevahel ise koostööseminari „Intestinum“ käigus algatati mõte käivitada Eestis kolorektaalvähi sõeluuringute programm, kasutades teiste maade kogemust ja uuringute tõenduspõhisust. Artiklis on toodud ülevaade soolevähi laboratoorsetest sõeluuringutest. Eesti Arst 2008; 87(7−8):541−54

Hematoloogiline analüüs: täiskasvanute referentsvahemikud ja kliiniliselt oluliste muutuste piirid

Hematoloogiliste testide paremaks hindamiseks ei piisa kirjanduses toodud “normidest” ega rakuloendajaid tootvate firmade soovitatud referentsväärtustest. Selles uurimuses on esmakordselt Eestis välja töötatud hematoloogiliste näitajate referentsväärtused ja kliiniliselt olulise muutuse piirid oma rahvastiku tervetel täiskasvanutel. Eesti Arst 2003; 82 (2): 452–45

Hematoloogilise automaatuuringu referentsväärtused Eesti täiskasvanutel

Taust ja eesmärk. Hematoloogiline automaatuuring (hemogramm) on üks kõige sagedasemaid uuringuid meditsiinilaboris. Kuigi paljudes Eesti laborites on hemogrammi uurimiseks kasutusel sama tootjafirma analüsaatorid, on referentsväärtused enamasti erinevad. Uuringu eesmärk oli välja töötada ühtsed hemogrammi populatsioonipõhised referentsväärtused Eesti täiskasvanutele. Metoodika. Referentsisikuteks kutsuti terved isikud ja vabatahtlikud esmased veredoonorid, kel ei esinenud kroonilisi haigusi ja kes ei tarvitanud ravimeid. Uuringumaterjaliks oli EDTA-veri. Proovid koguti neljas raviasutuses ja analüüsiti 3 tunni jooksul Sysmex XE- ja XN-seeria analüsaatoritel. Arvesse võeti ilma analüsaatori veateadeteta tulemused. Vereproovide põhjal ei tohtinud uuritaval olla põletikku ega latentset rauapuudust. Referentsvahemike leidmiseks kasutati mitteparameetrilist järkude meetodit, arvutati 90% usaldusvahemikud referentspiiridele. Tulemused. Analüüsiti 314 asümptomaatilise isiku vereproove, millest pärast väljaarvamiskriteeriumite rakendamist saadi andmeanalüüsiks 259 isiku tulemused (127 naist ja 132 meest). Leiti referentsvahemikud ja usalduspiirid järgmistele parameetritele: RBC (erütrotsüüdid), Hb (hemoglobiin), Hct (hematokrit), MCV (erütrotsüütide keskmine maht), MCH (keskmine hemoglobiini hulk erütrotsüüdis), MCHC (keskmine hemoglobiini kontsentratsioon erütrotsüüdis), RDW (erütrotsüütide suurusjaotuvus), Plt (trombotsüüdid), MPV (trombotsüütide keskmine maht), Pct (trombokrit), P-LCR (trombotsüütide suurte vormide suhtarv), PDW (trombotsüütide suurusjaotuvus), IPF (ebaküpsete trombotsüütide suhtarv), WBC (leukotsüüdid), IG# (ebaküpsed granulotsüüdid), Neut# (neutrofiilid), Lymph# (lümfotsüüdid), Mono# (monotsüüdid), Baso# (basofiilid), Eo# (eosinofiilid). Järeldused. Töötati välja Eesti täiskasvanute ühtsed populatsioonipõhised hemogrammi referentsväärtused. Uuringu tulemused võimaldavad referentsväärtusi laborites ühtlustada, et aidata kaasa patsiendi hemogrammi tulemuste täpsemale tõlgendamisele

Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations

Hypertension is a complex disease that affects a large proportion of adult population. Although approximately half of the inter-individual variance in blood pressure (BP) level is heritable, identification of genes responsible for its regulation has remained challenging. Genome-wide association study (GWAS) is a novel approach to search for genetic variants contributing to complex diseases. We conducted GWAS for three BP traits [systolic and diastolic blood pressure (SBP and DBP); hypertension (HYP)] in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) S3 cohort (n = 1644) recruited from general population in Southern Germany. GWAS with 395 912 single nucleotide polymorphisms (SNPs) identified an association between BP traits and a common variant rs11646213 (T/A) upstream of the CDH13 gene at 16q23.3. The initial associations with HYP and DBP were confirmed in two other European population-based cohorts: KORA S4 (Germans) and HYPEST (Estonians). The associations between rs11646213 and three BP traits were replicated in combined analyses (dominant model: DBP, P = 5.55 × 10–5, effect –1.40 mmHg; SBP, P = 0.007, effect –1.56 mmHg; HYP, P = 5.30 × 10−8, OR = 0.67). Carriers of the minor allele A had a decreased risk of hypertension. A non-significant trend for association was also detected with severe family based hypertension in the BRIGHT sample (British). The novel susceptibility locus, CDH13, encodes for an adhesion glycoprotein T-cadherin, a regulator of vascular wall remodeling and angiogenesis. Its function is compatible with the BP biology and may improve the understanding of the pathogenesis of hypertension

HYPEST study: profile of hypertensive patients in Estonia

<p>Abstract</p> <p>Background</p> <p>More than one third of adult population in Estonia has problems with elevated blood pressure (BP). The <it>Hypertension in Estonia </it>(HYPEST) study represents the country's first hypertension-targeted sample collection aiming to examine the epidemiological and genetic determinants for hypertension (HTN) and related cardiovascular diseases (CVD) in Estonian population. The HYPEST subjects (n = 1,966) were recruited across Estonia between 2004-2007 including clinically diagnosed HTN cases and population-based controls. The present report is focused on the clinical and epidemiological profile of HYPEST cases, and gender-specific effects on the pathophysiology of hypertension.</p> <p>Methods</p> <p>Current analysis was performed on 1,007 clinically diagnosed HTN patients (617 women and 390 men) aged 18-85 years. The hypertensives were recruited to the study by BP specialists at the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the Cardiology Clinic, Tartu University Hospital, Estonia. Longitudinal BP data was extracted retrospectively from clinical records. Current and retrospective data of patient's medical history, medication intake and lifestyle habits were derived from self-administrated questionnaire and each variable was examined separately for men and women. Eleven biochemical parameters were measured from fasting serum samples of 756 patients.</p> <p>Results</p> <p>The distribution of recruited men and women was 39% and 61% respectively. Majority of Estonian HTN patients (85%) were overweight (BMI ≥ 25 kg/m²) and a total of 79% of patients had additional complications with cardiovascular system. In men, the hypertension started almost 5 years earlier than in women (40.5 ± 14.5 vs 46.1 ± 12.7 years), which led to earlier age of first myocardial infarction (MI) and overall higher incidence rate of MI among male patients (men 21.2%, women 8.9%, <it>P </it>< 0.0001). Heart arrhythmia, thyroid diseases, renal tubulo-intestinal diseases and hyperlipidemia were more prevalent in hypertensive women compared to men (<it>P </it>< 0.0001). An earlier age of HTN onset was significantly associated with smoking (<it>P </it>= 0.00007), obesity (BMI ≥ 30 kg/m²; <it>P </it>= 0.0003), increased stress (<it>P </it>= 0.0003) and alcohol consumption (<it>P </it>= 0.004).</p> <p>Conclusion</p> <p>Understanding the clinical profile of HTN patients contributes to CVD management. Estonian hypertension patients exhibited different disease and risk profiles of male and female patients. This well-characterized sample set provides a good resource for studying hypertension and other cardiovascular phenotypes.</p

Õnnitlus. Dr Sirje Suuroja 70

Eesti Arst 2013; 92(1):4

Cas9-induced large deletions and small indels are controlled in a convergent fashion.

Repair of Cas9-induced double-stranded breaks results primarily in formation of small insertions and deletions (indels), but can also cause potentially harmful large deletions. While mechanisms leading to the creation of small indels are relatively well understood, very little is known about the origins of large deletions. Using a library of clonal NGS-validated mouse embryonic stem cells deficient for 32 DNA repair genes, we have shown that large deletion frequency increases in cells impaired for non-homologous end joining and decreases in cells deficient for the central resection gene Nbn and the microhomology-mediated end joining gene Polq. Across deficient clones, increase in large deletion frequency was closely correlated with the increase in the extent of microhomology and the size of small indels, implying a continuity of repair processes across different genomic scales. Furthermore, by targeting diverse genomic sites, we identified examples of repair processes that were highly locus-specific, discovering a role for exonuclease Trex1. Finally, we present evidence that indel sizes increase with the overall efficiency of Cas9 mutagenesis. These findings may have impact on both basic research and clinical use of CRISPR-Cas9, in particular in conjunction with repair pathway modulation