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11.
Wlodarska EK Konka M Zaleska T Ploski R Cedro K Pucilowska B Bekiesinska-Figatowska M Rydlewska-Sadowska W Ruzyllo W Hoffman P 《International journal of cardiology》2005,105(2):126-133
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritant disease with an autosomal dominant mode of transmission with incomplete penetrance and variable expression. Linkage analysis in affected families succeeds in identifying 9 loci determining 9 subtypes of the disease. Genotype phenotype correlation is unclear and the influence of various environmental factors is discussed. OBJECTIVES: Genotype phenotype correlation in 2 pairs of monozygotic twins with ARVC and the role of environmental factors are analyzed. PATIENTS AND METHODS: Among 40 pts with ARVC and their 195 relatives there were 2 pairs of monozygotic twins: brothers, age 47 y; and sisters, age 48 y. History, ECG, Holter monitoring, 2D and Doppler Echo, and MRI were analyzed. RESULTS: Twin brothers: ARVC was diagnosed in the proband after the episode of VT with LBBB morphology (enlarged right ventricle, focal hypokinesia of apex, MR evidence of adipose tissue in RV wall). Identical morphology of RV was seen in asymptomatic twin brother. The patient presenting arrhythmia has been rowing for 4 years. Twin sisters: diagnosis was done during family screening. Both were asymptomatic. RV morphology typical for ARVC was found discrete in one of them (bulges adipose tissue in the RV apex); the latter showed changes suggesting RV abnormality (mild segmental dilatation of infundibulum, adipose tissue in a free wall of the RV). No differences in previous viral infections and sports involvement were observed. CONCLUSIONS: 1. Clinical picture of ARVC in monozygotic twins is not identical. 2. Strenuous effort may be a factor triggering the arrhythmia in pts with ARVC. 相似文献
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Concurrent DNA Copy‐Number Alterations and Mutations in Genes Related to Maintenance of Genome Stability in Uninvolved Mammary Glandular Tissue from Breast Cancer Patients
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Piotr Madanecki Rafal Bartoszewski Magdalena Bałut Barbara Seroczyńska Kinga Kochan Adam Bogdan Małgorzata Butkus Rafał Pęksa Magdalena Ratajska Alina Kuźniacka Bartosz Wasąg Magdalena Gucwa Maciej Krzyżanowski Janusz Jaśkiewicz Zbigniew Jankowski Lars Forsberg J. Renata Ochocka Janusz Limon Michael R. Crowley Patrick G. Buckley Ludwine Messiaen Jan P. Dumanski Arkadiusz Piotrowski 《Human mutation》2015,36(11):1088-1099
Somatic mosaicism for DNA copy‐number alterations (SMC‐CNAs) is defined as gain or loss of chromosomal segments in somatic cells within a single organism. As cells harboring SMC‐CNAs can undergo clonal expansion, it has been proposed that SMC‐CNAs may contribute to the predisposition of these cells to genetic disease including cancer. Herein, the gross genomic alterations (>500 kbp) were characterized in uninvolved mammary glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array‐based comparative genomic hybridization showed 10% (6/59) of patients harbored one to 359 large SMC‐CNAs (mean: 1,328 kbp; median: 961 kbp) in a substantial portion of glandular tissue cells, distal from the primary tumor site. SMC‐CNAs were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC‐CNAs indicating genomic destabilization. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations and rare variants in genes related to maintenance of genomic integrity: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro), and TP53 (p.Arg306*). Co‐occurrence of gross SMC‐CNAs along with point mutations or rare variants in genes responsible for safeguarding genomic integrity highlights the temporal and spatial neoplastic potential of uninvolved glandular tissue in breast cancer patients. 相似文献
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Anna Kablak-Ziembicka Tadeusz Przewlocki Piotr Pieniazek Piotr Musialek Rafal Motyl Zbigniew Moczulski Wieslawa Tracz 《Journal of endovascular therapy》2006,13(2):205-213
PURPOSE: To assess flow velocities in the cerebral arteries after carotid artery stenting (CAS) in patients with unilateral versus bilateral lesions and analyze velocities in patients with neurological complications after CAS. METHODS: Ninety-two patients (68 men; mean age 63.2 +/- 8.4 years, range 44-82) with internal carotid artery (ICA) stenoses were divided according to unilateral (group I, n = 72) or bilateral (group II, n = 20) disease. Fifty age- and gender-matched patients without lesions in the extra- or intracranial arteries served as a control group. Transcranial color-coded Doppler ultrasound was performed prior to and within 24 hours after CAS in the test groups; systolic velocities were assessed ipsilateral (i) and contralateral (c) to the CAS site in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). RESULTS: Collateral flow via the anterior communicating artery (ACoA) was found in all group-II patients and 90% of group-I patients. After CAS, collateral flow through the ACoA ceased, and the velocity increased by 26% in the iMCA in group I compared to controls (p < 0.001). In group II, iMCA flow increased by 30% (p < 0.001) and flow via the ACoA (p < 0.001) increased, resulting in normalization of cMCA velocities (p = 0.928). In 89 (96.7%) subjects, CAS was uncomplicated. Hyperperfusion syndrome occurred in 2 (2.2%) patients, both with bilateral ICA stenoses; 1 (1.1%) transient ischemic attack was seen in a patient with unilateral disease. In the patients with hyperperfusion syndrome, the MCA velocities were 2.7- and 7.4-fold higher, respectively, versus before CAS and 2-fold higher than in controls. CONCLUSION: Uncomplicated CAS results in an iMCA velocity increase >25% compared to controls. MCA velocities in hyperperfusion syndrome were greatly increased versus before CAS and in controls. 相似文献
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Create a Chain of Survival: Extracorporeal Life Support Treatment of Severe Hypothermia Victims
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Rafal Pokrowiecki 《Drug delivery》2018,25(1):1504-1515
Along with the development of nanotechnological strategies for biomaterials associated with the prevention of infections, a myriad of clinically unproven techniques have been described to date. In this work, the aim was to perform a critical analysis of the literature available concerning antibacterial biomaterials for oral implantology and to provide a practical derivation for such a purpose. As anti-adhesive strategies may affect osseointegration, they should no longer be recommended for inclusion in this class of biomaterials, despite promising results in biomedical engineering for other, non-bone load bearing organs. Targeted, antibacterial drug delivery is most likely desirable in the case of intraosseous implants. Interfering factors such as the oral cavity environment, saliva, the bacterial microbiome, as well as, the characteristics of the alveolar mucosa and peri-implant space must be taken into account when calculating the local pharmacokinetics for antibacterial coatings. Effective release is crucial for tailoring antibacterial implant longevity providing minimal inhibitory concentration (MIC) for the desired amount of time, which for oral implants, should be at least the cumulative time for the osseointegration period and functional loading period within the tissues. These parameters may differ between the implant type and its anatomical site. Also, the functional drug concentration in the peri-implant space should be calculated as the amount of the drug released from the implant surface including the concentration of the drug inactivated by biological fluids of the peri-implant space or saliva flow throughout the effective release time. 相似文献
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Rafal Suwinski 《Journal of thoracic disease》2021,13(5):3315
It was commonly assumed in the past that blood-brain barrier could efficiently prohibit penetration of large peptide molecules, such as monoclonal antibodies, including programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. This belief has been recently revised by studies that demonstrate the presence of functional lymphatic vessels lining the dural sinuses. Furthermore, the activated circulating T cells have been shown to cross the blood-brain barrier. Such observations created strong rationale for attempts of immunotherapy for patients with brain metastases, used either alone or in combination with radiotherapy. The expected benefit from immunotherapy particularly refers to patients without targetable “driver” mutations who are not considered as candidates for novel targeted therapies. Current inference on efficacy and safety of combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) origins, in most, from the retrospective studies. The existing data suggest that use of immune checkpoint inhibitors (ICIs) with brain radiotherapy improves patients outcome, compared to brain radiotherapy alone. The available data also suggest that concurrent use of ICI and stereotactic radiation therapy (SRT) for brain metastases from NSCLC is tolerable and appears more effective than sequential combination of radiotherapy and ICI. Use of steroids appeared detrimental. Since a dependence between the risk of adverse events and type of ICI therapy as well as tumor pathology was found, further studies are required to establish optimal dosage, selection of drugs and sequence of ICI and brain radiotherapy in patients with brain metastases from NSCLC. 相似文献