Corticobasal syndrome (CBS) is clinically characterized by progressive asymmetric rigidity and apraxia together with symptoms suggestive of cortical involvement and basal ganglia dysfunction. The spectrum of neurodegenerative diseases that can manifest with CBS is wide. The associations of CBS with corticobasal degeneration, progressive supranuclear palsy, Alzheimer's disease, frontotemporal lobar degenerations, Creutzfeldt-Jakob disease, or diffuse Lewy body pathology have been reported. We describe the case of a 71-year-old woman with CBS. The histopathological examination of brain tissue revealed concomitant pathology corresponding to the limbic stage of Lewy-related pathology and the intermediate stage of Alzheimer's-type pathology. To date, there have been only a few cases with a similar combination of pathology manifesting with the CBS phenotype that have been described in the literature. The extent and distribution of pathological changes in these cases were somewhat different from ours, and significance for clinical manifestation was attributed to only one of these pathologies. In our case, we assume that both types of pathology contributed to the development of the disease, considering the presumed specific spread of both types of pathological processes according to Braak's staging. Our case expands the spectrum of neurodegenerative pathological processes that may manifest with the typical CBS phenotype. Also, it points out the importance of identifying specific biomarkers that would enable more accurate in vivo differential diagnosis and more accurate determination of the underlying pathological processes of these diseases.

• Publikační typ
• kazuistiky MeSH

Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis. DESIGN: The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined. CONCLUSIONS: No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer.

• MeSH
• adenokarcinom farmakoterapie   chirurgie   radioterapie   MeSH
• adjuvantní chemoterapie MeSH
• adjuvantní radioterapie MeSH
• deoxycytidin analogy a deriváty   terapeutické užití   MeSH
• fluoruracil analogy a deriváty   terapeutické užití   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádory rekta farmakoterapie   chirurgie   radioterapie   MeSH
• neoadjuvantní terapie MeSH
• prognóza MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

The Heidenhain form of Creutzfeldt-Jakob disease (CJD) is a rare CJD variant with predominantly visual symptoms in the early stages. Clinical manifestations of metamorphopsia, hemianopia and Balint's syndrome correlate with the involvement of the posterior cortical regions. A 71-year old healthy and very active man was admitted because of impaired visual acuity, hemianopia, and gait disturbance progressing over one week. MRI found typical cortical hyperintensities in the occipital regions while rhythm slowing and sharp waves were seen in the occipital regions on EEG. Protein 14-3-3 was detected in the cerebrospinal fluid. Postmortem neuropathology revealed typical histopathological changes consistent with CJD. Moreover, we found deposits of phosphorylated tau protein in the limbic regions that met the criteria for primary age-related tauopathy (PART); representing an additional and interesting finding in our case.

• MeSH
• Creutzfeldtova-Jakobova nemoc diagnóza   patologie   MeSH
• diferenciální diagnóza MeSH
• difuzní magnetická rezonance MeSH
• elektroencefalografie MeSH
• fatální výsledek MeSH
• fosforylace MeSH
• komorbidita MeSH
• lidé MeSH
• mozek patologie   MeSH
• neurologické vyšetření MeSH
• poruchy zraku diagnóza   patologie   MeSH
• proteiny 14-3-3 MeSH
• proteiny tau chemická syntéza   MeSH
• senioři MeSH
• tauopatie diagnóza   patologie   MeSH
• týlní lalok patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

INTRODUCTION: Calcific aortic valve stenosis (CAVS) is a serious clinical problem. The strongest predictor of CAVS progression is the amount of calcium in the aortic valve. The pathogenesis of CAVS is largely consistent with the pathogenesis of atherosclerosis; however, about 50% of patients with CAVS do not exhibit significant atherosclerosis. Cardiovascular calcification is currently considered an actively regulated process, in which the important role is attributed to the RANKL/RANK/OPG (receptor activator of nuclear factor κB ligand/RANK/osteoprotegerin) axis. We measured OPG levels in the tissue of calcified, stenotic aortic valves in relation to the presence or absence of coronary artery disease (CAD). MATERIALS AND METHODS: Aortic valve samples were collected from 105 patients with calcified, mainly severe aortic stenosis, who were divided into two groups according to the presence of CAD. In Group A (n=44), there were normal coronary artery findings, while in Group B (n=61), there was angiographically demonstrated >50% stenosis of at least one coronary artery. The control Group C (n=21) consisted of patients without aortic stenosis and with normal angiographic findings on coronary arteries. RESULTS: The highest tissue concentrations of OPG [median (pmol/L), 25th-75th percentile] were found in Group A [6.95, 3.96-18.37], which was significantly different compared to the other two groups (P=.026 and .001, respectively). The levels of OPG in Group B [4.15, 2.47-9.16] and in Group C [2.25, 1.01-5.08] did not differ significantly (P=.078); however, the lowest concentrations of OPG were found in Group C. Neither age nor gender in our study had effect on tissue levels of OPG (P=.994 for gender; P=.848 for age). CONCLUSION: Calcified and narrowed aortic valves, compared to the normal valves, were accompanied by a change in tissue concentrations of OPG, which is, in addition, dependent on the presence or absence of CAD. The highest tissue concentrations of OPG in our work were found in patients with significant aortic stenosis without concomitant CAD.

• MeSH
• aortální chlopeň metabolismus   patologie   MeSH
• aortální stenóza komplikace   metabolismus   patologie   MeSH
• ELISA MeSH
• kalcinóza komplikace   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen komplikace   metabolismus   patologie   MeSH
• osteoprotegerin analýza   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection. Meanwhile harmonized staging systems emerged in order to increase inter rater reproducibility. Therefore, a refined definition of Alzheimer's disease was recommended., a clearer picture of the neuropathological lesions diversity emerged secondarily to the systematic assessment of concomitant pathology highlighting finally a low rate of pure AD pathology. This brings new challenges to laboratory medicine in the field of cerebrospinal fluid (CSF) markers of Alzheimer's disease: how to further validate total Tau, phospho-TAU, Aß40 and Aß42 and new marker level cut-offs while autopsy rates are declining?

• MeSH
• Alzheimerova nemoc diagnóza   patologie   MeSH
• amyloidní beta-protein normy   MeSH
• biologické markery chemie   MeSH
• fosforylace MeSH
• lidé MeSH
• mozek patologie   MeSH
• progrese nemoci MeSH
• proteiny tau chemie   normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Fibrotic diseases are a group of pathologies with high incidence and mortality. Despite extensive research efforts, effective therapies are still not available. Understanding the molecular mechanisms driving the onset, progression and possible resolution of fibrosis is a prerequisite to the development of successful therapies. The central role of the TGF-β pathway and myofibroblasts in the pathogenesis of fibrosis is now generally accepted. The possible mechanisms of myofibroblast elimination or dedifferentiation, on the other hand, are still almost uncharted territory. Here we show that sustained expression of some components of MAPK signaling pathway (PDGFB, Ha-Ras(G12V) or the transcription factor EGR4) in primary chicken embryo dermal myofibroblasts results in a loss of autocrine TGF-β signaling and suppression of the myofibroblastic phenotype, characterized by the loss of alpha smooth muscle actin fibers and a substantial reduction in the production of extracellular matrix. Detailed analysis of the possible molecular mechanisms employed by EGR4 revealed FOXG1, BAMBI, NAB1, NAB2 and DUSP5 genes forming an EGR4 regulated network counteracting autocrine TGF-β signaling. We have also found that a combination of chemical inhibition of TGF-β signaling and perturbation of MAPK signaling with phorbol ester mimics the anti-fibrotic effects of PDGFB, Ha-Ras(G12V) and EGR4.

• MeSH
• aktiny genetika   metabolismus   MeSH
• dediferenciace buněk * MeSH
• forbolové estery farmakologie   MeSH
• kuřecí embryo MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• myofibroblasty cytologie   metabolismus   MeSH
• signální transdukce MeSH
• transformující růstový faktor beta metabolismus   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: Hereditary spherocytosis is an autosomal dominant inheritance disorder of the red blood cell membrane characterized by the presence of spherical-shaped erythrocytes (spherocytes) in the peripheral blood. The main clinical features include haemolytic anemia, variable jaundice, splenomegaly and cholelithiasis caused by hyperbilirubinemia from erythrocyte hemolysis. Splenectomy does not solve the congenital genetic defect but it stops pathological hemolysis in the enlarged spleen. If gallstones are present, it is appropriate to perform cholecystectomy at the time of splenectomy, although the patient has symptoms of gall bladder disease. We present the case of single incision laparoscopic surgical (SILS) concomitant splenectomy and cholecystectomy performed with conventional laparoscopic instruments in an 11-year-old girl with the diagnosis of hereditary spherocytosis. METHODS: A 2-3 cm umbilical incision was used for the placement of two 5 mm trocars and one 10 mm flexible videoscope. Conventional laparoscopic dissector, grasper, Ligasure, Harmonic Ace and hemoclips were the main tools during surgical procedure. We prefer Single Incision Laparoscopic Surgery Foam Port (Covidien) as the single umbilical device for introduction into the abdominal cavity. First, we performed cholecystectomy, then the gallbladder was put aside over the liver and after that we peformed splenectomy. To remove the detached spleen and gallbladder, a nylon extraction bag is introduced through one of the port sites. The spleen is than morcellated in the bag with forceps and removed in fragments. After that we removed them and the umbilical fascial incision was closed. RESULT: Splenectomy is the only effective therapy for this disorder and often it is performed in combination with cholecystectomy. Conventional surgery requires a wide upper abdominal incision for correct exposure of the gallbladder and spleen. Our experience shows that SILS splenectomy and cholecystectomy is feasible even in young children and despite the small number of cases in the world, we consider the combined laparoscopic approach safe and effective for the treatment of hereditary spherocytosis. CONCLUSION: According to actually published guidelines, the laparoscopic approach to concomitant splenectomy and cholecystectomy is recommended, but it depends on the availability of appropriately trained surgeons and suitable equipment.

• MeSH
• cholecystektomie laparoskopická MeSH
• dědičná sférocytóza chirurgie   MeSH
• dítě MeSH
• laparoskopie metody   MeSH
• lidé MeSH
• splenektomie * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Slovenská republika MeSH

Interactions between prion protein (PrP) and tau protein have long been discussed, especially in relation to the pathogenesis of neurodegenerative diseases. The presence of tauopathy in the genetic forms of Creutzfeldt-Jakob disease (CJD) brains is not uncommon. Molecular interactions between PrP and tau protein have been demonstrated in animal models; the role is attributed to the structural properties of misfolded isoform of the host-encoded prion protein (PrPSc) aggregates, especially amyloid, which contributes to the phosphorylation of tau protein, which is reflected in the frequent occurrence of tau pathology in inherited prion amyloidoses. The question is the relationship between PrPSc and hippocampal tau pathology without amyloid deposits (i.e. PART and ARTAG) in sporadic CJD (sCJD). The co-occurrence of these two proteinopathies in sCJD brains is quite rare. These pathological entities have been described in only a few cases of sCJD, all of them were older than 70 years. There have been speculations about the possibility of accelerating the course of pre-existing tauopathy or the possibility of accelerating the ageing process in the CJD brains. Here we present the clinical course and neuropathological findings of a patient with sCJD in whom the above mentioned tauopathies PART and ARTAG, considered to be typical for older age, were found as early as 58 years of age. According to the available information, this case represents an unusually early occurrence of age-related tauopathies not only in relation to sCJD, but also in general.

• MeSH
• Creutzfeldtova-Jakobova nemoc * genetika   MeSH
• lidé MeSH
• mozek metabolismus   MeSH
• prionová bílkovina genetika   MeSH
• priony * genetika   metabolismus   MeSH
• senioři MeSH
• tauopatie * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Súčasný výskyt ochorenia koronárnych artérii a ochorenia chlopní srdca je významným rizikovým faktorom u pacientov podstupujúcich resekčný výkon na pľúcach. Možnosť vykonať konkomitantnú (simultánnu) operáciu srdca aj pľúc je pre týchto pacientov vhodnou možnosťou. V prezentovanom prípade bola vykonaná intervencia na dvoch srdcových chlopniach, vykonaný bol trojnásobný aortokoronárny bypass a resekcia pľúc. Podobný chirurgický výkon doposiaľ publikovaný nebol. Kazuistika prezentuje 68-ročnú pacientku s trojcievnym koronárnym postihnutím, stredne závažnou stenózou aortálnej chlopne, závažnou insuficienciou trikuspidálnej chlopne, tumorom ľavého horného laloka pľúc. Pacientka podstúpila kombinovaný kardiochirurgický a torakochirurgický výkon, náhradu aortálnej chlopne, plastiku trikuspidálnej chlopne, trojnásobný aortokoronárny bypass a ľavú hornú lobektómiu pľúc. Na ôsmy pooperačný deň bola pacientka v stabilnom stave prepustená a v čase publikovania práce je v ambulantnom sledovaní. Simultánna operácia srdca a resekcia pľúc pre malignitu sa stáva štandardom liečebného postupu u pacientov, ktorí vyžadujú oba chirurgické zákroky. Najčastejším chirurgickým prístupom je stredná sternotómia, ktorá ponúka najlepší prístup pre kardiochirurgickú časť operácie a prijateľný prístup pre resekciu pľúc. Výnimku predstavuje lokalizácia tumoru v ľavom dolnom laloku pľúc, kedy je nutné použiť prístup torakotómiou, alebo častejšie vykonávať resekčný výkon na pľúcach počas mimotelového obehu. Ak použitie mimotelového obehu počas resekcie pľúc nie je nutné, väčšina autorov doporučuje prevedenie resekčného výkonu na pľúcach pred napojením pacienta na mimotelový obeh.

Coexisting coronary artery disease and significant heart valve disease represent a considerable risk factor in patients undergoing pulmonary resection. The possibility to perform concomitant (simultaneous) heart and lung surgery could be a good option for many patients. In the presented case report, the intervention was performed on two valves, triple coronary artery bypass and pulmonary resection, which has not been published in literature to date. A 68-year-old woman with coronary artery disease, aortic valve stenosis, tricuspid valve regurgitation and pulmonary disease (malignant pathology) presented with triple vessel disease, moderate aortic valve stenosis, severe tricuspid regurgitation and tumorous infiltration in the upper lobe of the left lung. She underwent combined heart and pulmonary surgery – left upper lobectomy, aortic valve replacement, tricuspid valve repair and coronary artery bypass surgery. On the eighth day of surgery, she was discharged. She continues to do well on follow-up. Simultaneous cardiac surgery and pulmonary resection for malignancy become almost standard treatment of patients who require heart and lung surgery. The most often approach is midline sternotomy that enables a comfortable cardiac intervention as well as an acceptable access to lungs. The left lower lobectomy remains an exception, in which pulmonary resection during extracorporeal circulation (ECC) is more often an option of left thoracotomy. If the use of ECC is inevitable, some authors prefer pulmonary resection before starting up ECC if the location of the neoplasm does not require resection during ECC.

• MeSH
• chirurgická náhrada chlopně metody   MeSH
• hrudní chirurgické výkony * metody   MeSH
• komorbidita * MeSH
• koronární bypass metody   MeSH
• lidé MeSH
• mimotělní oběh využití   MeSH
• nádory plic * chirurgie   komplikace   MeSH
• nemoci srdečních chlopní * diagnóza   chirurgie   komplikace   MeSH
• senioři MeSH
• trikuspidální insuficience chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

This work is intended to study the effect of preoperative capecitabine and radiotherapy treatment on the levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) mRNAs in rectal carcinoma. 55 patients with locally advanced rectal carcinoma (cT3-4, N0, M0 or cT2-4,N+, M0) were treated with capecitabine 825 mg/m2 twice a day and pelvic radiotherapy 1,8 Gy daily up to cumulative dose of 45 Gy, boosting up to 50,4 Gy. Patients underwent surgery 6th week after the completion of chemoradiotherapy. Biopsies of rectal carcinoma were taken before starting therapy and 14 days after its cesation. Biopsies were examined for TS, DPD and TP mRNA levels. CEA in serum was examined to monitor relapses. Both TP and TS mRNA increase two weeks after starting therapy (p<0,001). TP mRNA median levels were elevated 2,3x after starting therapy. Moreover responders exhibit 1,5x higher induction than non-responders both before and after starting therapy, but difference is significant before therapy only (p=0,017). Non-responders have most frequent TS induction. Complete remission was observed in 17% and substantial responses with microscopic residuum only in additional 19% of cases were achieved. The pathologic downstaging rate was 76%. Our data show that TS and TP mRNA are induced by preoperative chemoradiotherapy in both responders and nonresponders. TP induction is in accordance with the expected role of TP in the activation of capecitabine and the known promoting role of TP in tissue fibrosis frequently associated with tumor regression.

• MeSH
• deoxycytidin aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• fluoruracil analogy a deriváty   terapeutické užití   MeSH
• genetické markery MeSH
• karcinoembryonální antigen krev   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• nádory rekta MeSH
• polymerázová řetězová reakce MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• pyrimidiny metabolismus   MeSH
• senioři MeSH
• staging nádorů MeSH
• thymidinfosforylasa genetika   MeSH
• thymidylátsynthasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH