Random-regression models (RRM) are used in national genetic evaluations for longitudinal traits. The outputs of RRM are an index based on random-regression coefficients and its reliability. The reliabilities are obtained from the inverse of the coefficient matrix of mixed model equations (MME). The reliabilities must be approximated for large datasets because it is impossible to invert the MME. There is no extensive literature on methods to approximate the reliabilities of RRM when genomic information is included by single-step GBLUP. We developed an algorithm to approximate such reliabilities. Our method combines the reliability of the index without genomic information with the reliability of a GBLUP model in terms of effective record contributions. We tested our algorithm in the 3-lactation model for milk yield from the Czech Republic. The data had 30 million test-day records, 2.5 million animals in the pedigree, and 54,000 genotyped animals. The correlation between our approximation and the reliabilities obtained from the inversion of the MME was 0.98, and the slope and intercept of the regression were 0.91 and 0.02, respectively. The elapsed time to approximate the reliabilities for the Czech data was 21 min.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed. MATERIAL AND METHODS: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings. RESULTS: The medians of TFRC in all individual participating centers were > 12 weeks (range 14.0-36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks). CONCLUSION: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

• Klíčová slova
• Chemotherapy, chemother­apy, colorectal cancer,
• MeSH
• cetuximab * terapeutické užití   MeSH
• kolorektální nádory * farmakoterapie   patologie   genetika   MeSH
• leukovorin terapeutické užití   MeSH
• lidé MeSH
• prospektivní studie MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• studie proveditelnosti * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• cetuximab * MeSH
• leukovorin MeSH
• protinádorové látky imunologicky aktivní MeSH

Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

• MeSH
• colon transversum * chirurgie   MeSH
• kolorektální nádory * mozkomíšní mok   chirurgie   MeSH
• lidé MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Estimated breeding values (EBVs) and genomic enhanced breeding values (GEBVs) for milk production of young genotyped Holstein bulls were predicted using a conventional BLUP - Animal Model, a method fitting regression coefficients for loci (RRBLUP), a method utilizing the realized genomic relationship matrix (GBLUP), by a single-step procedure (ssGBLUP) and by a one-step blending procedure. Information sources for prediction were the nation-wide database of domestic Czech production records in the first lactation combined with deregressed proofs (DRP) from Interbull files (August 2013) and domestic test-day (TD) records for the first three lactations. Data from 2627 genotyped bulls were used, of which 2189 were already proven under domestic conditions. Analyses were run that used Interbull values for genotyped bulls only or that used Interbull values for all available sires. Resultant predictions were compared with GEBV of 96 young foreign bulls evaluated abroad and whose proofs were from Interbull method GMACE (August 2013) on the Czech scale. Correlations of predictions with GMACE values of foreign bulls ranged from 0.33 to 0.75. Combining domestic data with Interbull EBVs improved prediction of both EBV and GEBV. Predictions by Animal Model (traditional EBV) using only domestic first lactation records and GMACE values were correlated by only 0.33. Combining the nation-wide domestic database with all available DRP for genotyped and un-genotyped sires from Interbull resulted in an EBV correlation of 0.60, compared with 0.47 when only Interbull data were used. In all cases, GEBVs had higher correlations than traditional EBVs, and the highest correlations were for predictions from the ssGBLUP procedure using combined data (0.75), or with all available DRP from Interbull records only (one-step blending approach, 0.69). The ssGBLUP predictions using the first three domestic lactation records in the TD model were correlated with GMACE predictions by 0.69, 0.64 and 0.61 for milk yield, protein yield and fat yield, respectively.

• Klíčová slova
• animal model, dairy cattle, genomic breeding value, single-step prediction, test-day model,
• MeSH
• chov * MeSH
• genom genetika   MeSH
• genomika * MeSH
• genotyp MeSH
• laktace MeSH
• mléko metabolismus   MeSH
• regresní analýza MeSH
• skot genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot genetika   fyziologie   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The purpose of our study was to develop an approximation procedure to estimate reliabilities of single-step genomic BLUP breeding values in a test-day model for routine evaluation of milk yield in a dairy cattle population. Input data consisted of 20,220,047 first-, second-, and third-lactation test-day milk yield records of 1,126,102 Czech Holstein cows (each lactation being considered a separate trait), with 1,844,679 animals in the pedigree file and with genomic data from 2,236 bulls. Evaluation was according to a multi-lactation model. The procedure was based on the effective number of records per animal from milk recording as well as from genomic and pedigree relationships. Traits were analyzed individually, and genetic covariances among traits were subsequently taken into account. The use of genomic information increased average reliability in young bulls from 0.276 to 0.505, but increased reliability in proven bulls only from 0.828 to 0.855. The reliabilities of genomic breeding values in multi-trait evaluation for first, second and third lactations, respectively, averaged 0.652, 0.673, and 0.633 for young bulls and 0.907, 0.894, and 0.852 for proven bulls. For an index combining all 3 lactations, the average reliability of a single-step genomic BLUP prediction was 0.712 and 0.925 for younger and proven bulls, respectively. Increased reliability due to genotyping in the population of all genotyped and nongenotyped animals was very small (<0.01) because of the small proportion of genotyped animals in the population.

• Klíčová slova
• genomic prediction, reliability, single-step genomic BLUP, test-day model,
• MeSH
• chov metody   MeSH
• fenotyp MeSH
• genom * MeSH
• laktace * MeSH
• mlékárenství metody   MeSH
• mléko metabolismus   MeSH
• modely genetické MeSH
• reprodukovatelnost výsledků MeSH
• skot genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot genetika   fyziologie   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Estimated breeding values (EBV) for first-lactation milk production of Holstein cattle in the Czech Republic were calculated using a conventional animal model and by single-step prediction of the genomic enhanced breeding value. Two overlapping data sets of milk production data were evaluated: (1) calving years 1991 to 2006, with 861,429 lactations and 1,918,901 animals in the pedigree and (2) calving years 1991 to 2010, with 1,097,319 lactations and 1,906,576 animals in the pedigree. Global Interbull (Uppsala, Sweden) deregressed proofs of 114,189 bulls were used in the analyses. Reliabilities of Interbull values were equivalent to an average of 8.53 effective records, which were used in a weighted analysis. A total of 1,341 bulls were genotyped using the Illumina BovineSNP50 BeadChip V2 (Illumina Inc., San Diego, CA). Among the genotyped bulls were 332 young bulls with no daughters in the first data set but more than 50 daughters (88.41, on average) with performance records in the second data set. For young bulls, correlations of EBV and genomic enhanced breeding value before and after progeny testing, corresponding average expected reliabilities, and effective daughter contributions (EDC) were calculated. The reliability of prediction pedigree EBV of young bulls was 0.41, corresponding to EDC=10.6. Including Interbull deregressed proofs improved the reliability of prediction by EDC=13.4 and including genotyping improved prediction reliability by EDC=6.2. Total average expected reliability of prediction reached 0.67, corresponding to EDC=30.2. The combination of domestic and Interbull sources for both genotyped and nongenotyped animals is valuable for improving the accuracy of genetic prediction in small populations of dairy cattle.

• MeSH
• chov metody   statistika a číselné údaje   MeSH
• genetické markery genetika   MeSH
• genomika metody   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kvantitativní znak dědičný MeSH
• laktace genetika   MeSH
• mlékárenství metody   statistika a číselné údaje   MeSH
• rodokmen MeSH
• skot genetika   fyziologie   MeSH
• záznamy jako téma veterinární   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot genetika   fyziologie   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH

Pregnancy-associated plasma protein-A (PAPP-A) was described as a novel marker of acute coronary syndrome. The aim of our study was to investigate how serum pregnancy-associated plasma protein-A (PAPP-A) levels change in patients with ischaemic stroke and intracerebral haemorrhage and to evaluate if PAPP-A might be a marker not only of myocardial infarction but also a useful parameter in cerebrovascular disorders. 43 patients with acute cerebrovascular events were divided into 3 groups--patients with ischaemic stroke (n=16), patients with intracranial haemorrhage (n=10) and patients with both ischaemic stroke and coronary artery disease (n=17). The control group consisted of 12 subjects. PAPP-A was measured by TRACE (Time Resolved Amplified Cryptate Emission) technology. PAPP-A levels in patients with intracranial haemorrhage and those with both ischaemic stroke and coronary artery disease were increased in comparison with the control group (p<0.005, p<0.01, respectively) as well as with patients with ischaemic stroke only (p<0.01, p<0.05, respectively). A positive correlation between PAPP-A and total cholesterol in patients with both ischaemic stroke and coronary artery disease (r=0.497, p<0.05) was observed. Serum PAPP-A levels in all studied patients correlated positively with serum creatinine (r=0.395, p<0.05). PAPP-A levels are increased in patients with intracranial haemorrhage and in the patients whose ischaemic stroke is associated with coronary artery disease. The atherosclerotic process may contribute to increased serum PAPP-A levels. PAPP-A may be a marker of increased risk of atherothrombotic events in general.

• MeSH
• antikardiolipinové protilátky krev   MeSH
• biologické markery krev   MeSH
• cerebrovaskulární poruchy krev   diagnóza   MeSH
• cévní mozková příhoda krev   diagnóza   MeSH
• intrakraniální krvácení krev   diagnóza   MeSH
• lidé MeSH
• senioři MeSH
• těhotenský plazmatický protein A analýza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikardiolipinové protilátky MeSH
• biologické markery MeSH
• těhotenský plazmatický protein A MeSH

Paraneoplastic neurodegenerative diseases are defined as damage to central and peripheral nervous tissue related to a malignancy, in the absence of metastases. If they represent first disease manifestation, the diagnosis can pose a real problem. A case of 59-year-old woman is described, who suffered during her last nine months of life from meningoencephalitis, with cranial nerves pareses and progressive quadruparalysis. The CSF exhibited a temporary inflammatory response with slow improvement, whereas the clinical status progressed continually toward terminal bronchopneumonia. An extensive infectious agent search was negative. Though the result of the autoantibody panel available (anti Yo, Hu, Ri) was negative, the paraneoplastic degeneration remained a part of the differential diagnosis. Post-mortem examination revealed residual brain stem meningoencephalitis and advanced cerebellar loss of Purkinje cells, in the presence of a neuroendocrine small cell lung carcinoma in the right lower lobe. The carcinoma only manifested intravitally, with paratracheal lymphadenomegaly on imaging. Rapid progress in the diagnostics of autoimmune neurodegeneration with the increasing spectrum of autoantibody detection tools has recently increased the possibilities of revealing clinically silent, primary manifesting neurodegeneration. In the future, it may also represent a target for therapeutic intervention.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom komplikace   patologie   MeSH
• meningoencefalitida etiologie   patologie   MeSH
• nádory plic komplikace   patologie   MeSH
• paraneoplastické neurologické syndromy diagnóza   etiologie   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

Many neurological diseases cause permanent ventilatory insufficiency. In the ambulatory care we consider regular observation of these patients as a very important. The detection of the early clinical symptoms initialises early ventilatory support. We prefer non-invasive mechanical ventilatory methods to invasive ones. Invasive home care ventilation is very difficult and needs adequate social, medical and economical conditions. We present one case.

• MeSH
• dospělí MeSH
• lidé MeSH
• respirační insuficience etiologie   terapie   MeSH
• služby domácí péče poskytované nemocnicí * MeSH
• svalové dystrofie komplikace   MeSH
• ventilace umělá s výdechovým přetlakem * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

UNLABELLED: Between April 1994 and May 1997 103 breast cancer patients (pts), pT1c-3a, pN0-1, M0, were randomised after surgery to adjuvant tamoxifen (20 mg per day) or to tamoxifen plus CMF (C 500 mg/m2, M 40 mg/m2 and F 600 mg/m2 on days 1st and 8th q 28 day) in 6 cycles. The median age (49-72 years, median 58), tumour size, number of involved lymphnodes (0-3), estrogens receptor status, grade (I-III) and type of operation were well balanced among the 50 pts on tamoxifen and the 53 pts on tamoxifen plus CMF pts, preferably postmenopausal. RESULTS: Grade of toxicity according to WHO criteria was not higher then two in both arms. Toxicity both haematological and non-haematological was higher in the group treated with chemotherapy (0 vs 32 resp. 20%) except weight gain (52% in both group). After median follow-up of 42 mos five recurrences in tamoxifen and seven in tamoxifen plus CMF pts were observed (p = NS). The projected 3-y DFS is 92% for tamoxifen and 88% for tamoxifen plus CMF (p = NS). The 3-y OS is 88% for tamoxifen and 80% for tamoxifen plus CMF pts (p = NS). CONCLUSIONS: Both regimens are equally effective with higher toxicity in the group with combined chemo- and hormonal therapy.

• MeSH
• adjuvantní chemoterapie MeSH
• antitumorózní látky hormonální škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory prsu mortalita   radioterapie   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• tamoxifen škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antitumorózní látky hormonální MeSH
• tamoxifen MeSH