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991.
Sergey V. Nesterov Chunlei Han Maija Mäki Sami Kajander Alexandru G. Naum Hans Helenius Irina Lisinen Heikki Ukkonen Mikko Pietilä Esa Joutsiniemi Juhani Knuuti 《European journal of nuclear medicine and molecular imaging》2009,36(10):1594-1602
Purpose
Carimas? (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation using 15O-labelled water.Methods
Four observers with various levels of experience in nuclear medicine independently analysed 20 MP studies (10 rest flow: “rest”, 10 adenosine-induced hyperaemia: “stress”). Each study was analysed twice. The linear mixed model for repeated measures was fitted to the data to calculate intraclass correlation coefficients (ICC), differences between the repeats (the intraobserver differences) and differences between the observers (the interobserver differences). Also, Pearson correlation coefficients (r) were calculated and Bland-Altman plots were drawn. The reproducibility of MP was assessed on global, regional and segmental levels. Thereafter, this analysis was applied in 48 consecutive clinical patients with suspected coronary heart disease (CHD).Results
For the experienced observer the Pearson r for all segments was 0.974 at rest and 0.978 at stress (p?<?0.0001), and the repeatability coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per min (14.9%), correspondingly. The ICC reflected very good overall reproducibility. The intraobserver and interobserver differences were small, and the difference between the most and the least experienced observers at stress was 8.5% for the global MP. The clinical accuracy of the perfusion in the detection of CHD was excellent (positive predictive value 91% and negative predictive value 88%) against invasive angiography.Conclusion
The results demonstrate high reproducibility of myocardial perfusion quantitation with 15O-labelled water PET using Carimas?. The results support the feasibility of robust analysis and good clinical accuracy. 相似文献992.
Karoline V Gleixner Yüksel Filik Daniela Berger Christina Schewzik Gabriele Stefanzl Irina Sadovnik Lina Degenfeld-Schonburg Gregor Eisenwort Mathias Schneeweiss-Gleixner Konstantin Byrgazov Wolfgang R Sperr Jií Mayer Thomas Lion Peter Valent 《American journal of cancer research》2021,11(9):4470
Ponatinib is a tyrosine kinase inhibitor (TKI) directed against BCR-ABL1 which is successfully used in patients with BCR-ABL1 T315I+ chronic myeloid leukemia (CML). However, BCR-ABL1 compound mutations may develop during therapy in these patients and may lead to drug resistance. Asciminib is a novel drug capable of targeting most BCR-ABL1 mutant-forms, including BCR-ABL1T315I, but remains ineffective against most BCR-ABL1T315I+ compound mutation-bearing sub-clones. We demonstrate that asciminib synergizes with ponatinib in inducing growth-arrest and apoptosis in patient-derived CML cell lines and murine Ba/F3 cells harboring BCR-ABL1 T315I or T315I-including compound mutations. Asciminib and ponatinib also produced cooperative effects on CRKL phosphorylation in BCR-ABL1-transformed cells. The growth-inhibitory effects of the drug combination ‘asciminib+ponatinib’ was further enhanced by hydroxyurea (HU), a drug which has lately been described to suppresses the proliferation of BCR-ABL1 T315I+ CML cells. Cooperative drug effects were also observed in patient-derived CML cells. Most importantly, we were able to show that the combinations ‘asciminib+ponatinib’ and ‘asciminib+ponatinib+HU’ produce synergistic apoptosis-inducing effects in CD34+/CD38- CML stem cells obtained from patients with chronic phase CML or BCR-ABL1 T315I+ CML blast phase. Together, asciminib, ponatinib and HU synergize in producing anti-leukemic effects in multi-resistant CML cells, including cells harboring T315I+ BCR-ABL1 compound mutations and CML stem cells. The clinical efficacy of this TKI combination needs to be evaluated within the frame of upcoming clinical trials. 相似文献
993.
994.
995.
The Immunosuppressive Properties of the HIV Vpr Protein Are Linked to a Single Highly Conserved Residue, R90 下载免费PDF全文
996.
Pollard I 《Seminars in Fetal & Neonatal Medicine》2007,12(2):106-113
Epidemiological evidence suggests that an adverse prenatal environment can have profound long-term health consequences throughout postnatal life. This chapter discusses the underlying mechanisms implicated in the consumption of mood-altering recreational drugs and teratogenicity in the fetus. The way metabolic parameters in pregnancy influence the pharmacokinetic characteristics of drugs and alcohol and the developmental stage of neurotoxicity are reviewed. The general underlying mechanisms that link multifaceted interactions between drug characteristics, gene polymorphisms, dietary deficiencies, changed endocrine indices and fetal programming are outlined, with specific examples throughout the text. As developmental injury is of significant social concern, the final section questions whether society provides adequate support for making appropriate and informed lifestyle choices to alleviate preventable transgenerational harm. 相似文献
997.
998.
de Vries MC Rodenburg RJ Morava E van Kaauwen EP ter Laak H Mullaart RA Snoeck IN van Hasselt PM Harding P van den Heuvel LP Smeitink JA 《European journal of pediatrics》2007,166(3):229-234
Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or psychomotor developmental delay and hypotonia
were the most frequent clinical disease presentations in eight children with combined oxidative phosphorylation enzyme complex
deficiencies carrying mutations in the polymerase gamma (POLG1) gene. Five out of eight patients developed severe liver dysfunction during the course of the disease. Three of these patients
fulfilled the disease criteria for Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme complexes
I and III, in combination with complex II, complex IV and/or PDHc in muscle, whereas in fibroblasts normal enzyme activities
were measured. All children carried homozygous or compound heterozygous mutations in the POLG1 gene, including two novel mutations in association with mtDNA depletion. Conclusion We suggest performing POLG1 mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture
is not Alpers syndrome. 相似文献
999.
Nutman A Postovsky S Zaidman I Elhasid R Vlodavsky E Kreiss Y Ben Arush MW 《Pediatric hematology and oncology》2007,24(1):53-61
The authors describe the case of a 19-year-old female patient with a primary primitive neuroectodermal tumor (PNET) of the thoraco-lumbar spinal cord, who presented with acute urinary retention and back pain for 2 months. Magnetic resonance imaging revealed an intradural extramedullary tumor, 6.5 cm long, in the region of the conus medullaris. Histological examination disclosed a small round cell tumor with immunohistochemical characteristics of a peripheral PNET. Metastatic workup showed no evidence of an intracranial tumor or metastases outside the neuroaxis. The patient received multidisciplinary treatment, including surgical excision, irradiation of the entire cranio-spinal axis, and high-dose chemotherapy with autologous stem cell rescue. Presently, 24 months after diagnosis, the patient remains in complete remission. 相似文献
1000.
Caliskan M Gatti G Sosnovskikh I Rotmensz N Botteri E Musmeci S Rosali dos Santos G Viale G Luini A 《Breast cancer research and treatment》2008,112(3):513-521
Background Paget’s disease of the breast is an uncommon presentation of breast malignancy, accounting for 1–3% of all the breast tumors
and presents in different histopathologic patterns: in association with an underlying invasive or non invasive carcinoma,
or without any underlying neoplasia. In the literature, different methods are used for the treatment. Mastectomy with or without
axillary dissection has been considered as the standard treatment procedure for many years. Several studies have already shown
that breast conservation with radiation therapy is an oncologically safe option. Regarding the axillary approach, several
studies have documented the presence of positive sentinel lymph node even in Paget’s disease alone. The objective of this
study was to retrospectively analyze outcome of patients affected by Paget’s breast disease and to define our institutional
experience. Patients and methods Between May 1996 and February 2003, 114 patients with confirmed Paget’s disease of the breast were retrieved and underwent
surgery at the European Institute of Oncology of Milan, Italy. The median age of the patients was 54 years at the time of
the diagnosis. In our study, the histopathological examination of the operated specimen revealed one hundred seven patients
with Paget’s disease associated with an underlying invasive or non invasive carcinoma, and seven patients without underlying
carcinoma. Patients underwent either conservative breast surgery or mastectomy, with or without sentinel lymph node biopsy
and/or axillary surgery. Each patient was evaluated after surgery at a multidisciplinary meeting to selecting systemic therapy.
Results Seven patients had “pure” Paget’s disease of the breast and one hundred seven had the disease associated with an underlying
carcinoma. As surgical techniques 71 mastectomies and 43 breast conserving surgeries have been performed. Complete axillary
dissection was done in patients with clinically positive lymph node and/or sentinel lymph node biopsy positive. Sentinel lymph
node biopsy was performed in nineteen patients with invasive component and five were positive and underwent axillary dissection.
Eleven sentinel lymph node biopsies were done in patients with non invasive component and none of them was positive. Adjuvant
systemic therapies were based on the final tumor, node and metastasis stage: thirty patients received adjuvant chemotherapy
alone, fourteen received endocrine treatment alone, twenty-six patients were evaluated to receive both chemo and endocrine
therapy. The median duration of follow up was 73 months and was updated in the last 6 months. Five patients developed local
recurrence, one had regional recurrence, another two had loco-regional recurrences and fourteen had distant metastasis as
a first event. Malignancy-related deaths were censored in the statistical analyses cancer for and due to another tumor in
eleven patients. Additionally, deaths were not related to malignancy totally in thirteen patients. Conclusions Screening examination and imaging techniques are fundamental. Breast conserving surgery combined with breast irradiation
for patients with invasive and non invasive breast carcinoma has become the treatment of first choice. All surgical conservative
approaches should include the complete nipple–areolar complex and margins of resected specimen free of tumor. Thanks to the
evolution of the conservative approach, good cosmetic result can be obtained. To be informed about the axillary lymph node
status and to avoid the patient to have a second surgical approach, sentinel lymph node biopsy should be performed. 相似文献