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91.
p15INK4b, p14ARF, and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors. 总被引:1,自引:0,他引:1
Federica Perrone Silvia Tabano Federica Colombo Gianpaolo Dagrada Sarah Birindelli Alessandro Gronchi Maurizio Colecchia Marco A Pierotti Silvana Pilotti 《Clinical cancer research》2003,9(11):4132-4138
PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) can arise sporadically or in association with neurofibromatosis type 1. Deletions at the 9p21 locus have been reported in these tumors. To additionally characterize the status of this chromosomal region, in this study we performed a comprehensive, mostly PCR-based molecular analysis of the three tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) located at the 9p21 locus in 26 cryopreserved MPNSTs. EXPERIMENTAL DESIGN: Fourteen neurofibromatosis type 1-related and 12 sporadic cases were investigated for homozygous deletion coupled with fluorescent in situ hybridization, promoter methylation, and mutational analysis, as well as m-RNA expression. RESULTS: The results showed that an inactivation of one or more genes occurred in 77% of MPNSTs and was mainly achieved through homozygous deletion (46%), which, in turn, encompassed all of the three tandemly linked genes in 83% of the deleted cases. Promoter methylation was at a less extent involved in gene silencing (18%), and no mutations were found. Loss of function at DNA level strongly correlated with loss of mRNA expression accounting for 80% of the cases. Because of the close relationship between p14(ARF) and TP53 and between p15(INK4b)/p16(INK4a) and Rb, these results support a model of a coinactivation of TP53 and Rb pathways in 75% of MPNSTs, with functional consequences on cell growth control and apoptosis. CONCLUSIONS: The inactivation of the 9p21 locus is a frequent and peculiar hallmark of MPNST genetic profile leading also to an impaired apoptosis that could be taken into account in treatment planning of these tumors. 相似文献
92.
Arsenio Spinillo Consultant Ezio Capuzzo Clinical Assistant Gaia Piazzi Registrar Federica Baltaro Registrar Mauro Stronati Consultant Alessandra Ometto Consultant 《BJOG : an international journal of obstetrics and gynaecology》1997,104(6):668-673
Objective To estimate the risk of specific adverse neonatal events resulting from the combined effects of prematurity and low birthweight in very preterm infants (delivered at 24–31 weeks of gestation)
Design A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation.
Setting Pavia, Italy.
Population Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation.
Methods To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation.
Results After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS 0 ( 50th centile of birthweight), infants with birthweight SDS < −1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42–9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04–75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41–7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age.
Conclusions A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does. 相似文献
Design A cohort study of specific adverse neonatal events in preterm infants born at between 24 and 31 weeks of gestation.
Setting Pavia, Italy.
Population Two hundred and thirty singleton infants with sonographically confirmed gestational age, delivered at 24 to 31 weeks of gestation.
Methods To evaluate the impact of a lower than expected birthweight on selected neonatal events independently of gestational age, we calculated birthweight standard deviation scores (differences between actual birthweight and fitted birthweight divided by fitted standard deviation) for each week of gestation.
Results After adjustment for gestational age and other confounders, there was a significant linear trend relating a decreasing birthweight SDS to an increased likelihood of neonatal death, intraventricular haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with infants with SDS 0 ( 50th centile of birthweight), infants with birthweight SDS < −1 (< 16th centile) had increased odds for neonatal death [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.42–9.6], grade III-IV intraventricular haemorrhage (OR 17.5, 95% CI 4.04–75.9), and neonatal acidosis (OR 3.22, 95% CI 1.41–7.4). The significance of birthweight SDS as a predictor of neonatal outcome, however, was lower than that of gestational age.
Conclusions A lower than expected birthweight affects the likelihood of several adverse neonatal events in very preterm infants. However, a decreasing birthweight SDS affects neonatal outcome less than decreasing gestation does. 相似文献
93.
K. Subramaniam R.H. Eikelboom R. Marino M.D. Atlas G.P. Rajan 《Clinical otolaryngology》2006,31(4):273-279
Objectives: To determine the quality of life (QOL) after stapes surgery and whether audiological parameters for hearing correlate with specific QOL factors. Design: A retrospective cross‐sectional study. Setting: A tertiary referral centre. Participants: A series of 35 patients who underwent stapes surgery of which three were excluded because they were <18 years of age, chronically or mentally ill, or in a dependant relationship. Response rate was 93% (30/32). Nine were further excluded because they had revision or bilateral surgery, or missing data. Twenty‐one patients were included in this study. Main outcome measures: The Glasgow Benefit Inventory (GBI) was used to evaluate general QOL and the Hearing Disability and Handicap Scale (HDHS) was used as a disease‐specific measure. The Belfast Rule of Thumb and Glasgow Benefit Plot assessed hearing outcomes. Results: Operative success was 86% using the Belfast Rule of Thumb and 95% had closure of the air–bone gap to within 20 dB. 81.8% of patients reported a better overall QOL as surgery. Glasgow Benefit Inventory Social and GBI Physical scores correlated positively with the HDHS speech component (P < 0.05). The duration of hearing loss correlated inversely with the average HDHS score (P < 0.05). Conclusion: The majority of patients report a better QOL as undergoing stapes surgery. Speech impacts on people's physical and social QOL of patients. Quality of life tools, in addition to objective audiologic measurements can provide clinicians with patients’ subjective perspective that helps guide clinical decision‐making and counselling. 相似文献
94.
男性与女性糖尿病患者致死性冠心病的额外危险:37个前瞻性队列研究的汇总分析 总被引:6,自引:0,他引:6
目的:估计男性和女性糖尿病患者致死性冠心病的相对危险。设计:前瞻性队列研究的汇总分析。数据来源:自1966年至2005年3月间Embase和Medline确认并发表的研究,加上源自亚太队列研究协作组的研究,采用正文词组与MeSH主题词相结合的策略进行检索。综述方法:对入选研究的要求为报告有或无糖尿病的男性与女性致死性冠心病的相对危险比较的估计值。如果对估计值仅做年龄调整(而其它因素来经调整——泽者注),则将该研究排除在外。结果:总共纳入37项2型糖尿病和致死性冠心病的研究,涉及447064例患者。糖尿病患者的致死性冠心病发生率显著高于非糖尿病患者(5.4%比1.6%)。与无糖尿病者相比,糖尿病患者发生致死性冠心病的总的相对危险,女性为3.50,95%可信区间为2.70~4.53,显著高于男性患者(2.06,95%可信区间1.81~2.34)。在除外8项仅根据年龄调整的研究后,两性之间危险的差异大大减小,但仍然具有极显著统计学意义。汇集29项经多因素调整估计值的研究,总的相对危险比(女性比男性)为1.46(1.14~1.88)。结论:糖尿病相关的致死性冠心病相对危险,女性比男性高出50%。这种额外的冠心病危险可以通过女性糖尿病患者具有更多不利的心血管危险因素特点以及倾向于对男性患者更注重治疗的可能偏差来解释。 相似文献
95.
Nocturnal frontal lobe epilepsy (NFLE) has become clinically relevant in recent years. NFLE represents a spectrum of clinical manifestations, ranging from brief, stereotyped, sudden arousals, often recurring several times per night, sometimes with a quasi-periodic pattern, to more complex dystonic-dyskinetic seizures and to prolonged "somnambulic" behaviour. Episodes of increasing intensity have been labelled as paroxysmal arousal (PA), nocturnal paroxysmal dystonia (NPD) and episodic nocturnal wandering (ENW). NFLE affects both sexes with a higher prevalence for men, is frequently cryptogenetic and displays a strong familial trait for parasomnias and epilepsy (NFLE). Seizures appear more frequently between 14 and 20 years of age, but can affect any age and tend to increase in frequency during life. Interictal and ictal scalp electroencephalography (EEG) are often normal, the use of sphenoidal leads may be helpful. Carbamazepine taken at night is often effective at low doses, but a third of the patients are resistant to anti-epileptic drugs (AED) treatment. A familial form, characterized by an autosomal dominant transmission, has also been described. Autosomal dominant nocturnal frontal lobe epilepsy is a genetic variant of NFLE, in itself both clinically and biologically heterogeneous. NFLE should be suspected in the presence of frequent stereotyped paroxysmal nocturnal motor events arising or persisting into adulthood. Videopolysomnography is mandatory to confirm the diagnosis. 相似文献
96.
A Olivieri G Santini C Patti T Chisesi C De Souza A Rubagotti S Aversa A Billio A Porcellini M Candela R Centurioni A M Congiu M Brunori S Nati M Spriano R Vimercati G Marino A Contu L Tedeschi I Majolino M Crugnola M R Sertoli 《Annals of oncology》2005,16(12):1941-1948
BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT. 相似文献
97.
98.
Antonio Leone Marzia Marino Claudia Dell’Atti Viola Zecchi Nicola Magarelli Cesare Colosimo 《Rheumatology international》2016,36(10):1335-1346
The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine. 相似文献
99.
In vitro development of engineered muscle using a scaffold based on the pressure‐activated microsyringe (PAM) technique
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Daniele Cei Adriana Malena Carmelo de Maria Emanuele Loro Federica Sandri Giulia del Moro Sara Bettio Lodovica Vergani Giovanni Vozzi 《Journal of tissue engineering and regenerative medicine》2017,11(1):138-152
The development of new human skeletal muscle tissue is an alternative approach to the replacement of tissue after severe damage, for example in the case of traumatic injury, where surgical reconstruction is often needed following major loss of natural tissue. Treatment to date has involved the transfer of muscle tissue from other sites, resulting in a functional loss and volume deficiency of donor sites. Approaches that seek to eliminate these problems include the relatively new solution of skeletal muscle engineering. Here there are two main components to consider: (a) the cells with their regenerative potential; and (b) the polymeric structure onto which cells are seeded and where they must perform their activities. In this paper we describe well‐defined two‐ and three‐dimensional polymeric structures able to drive the myoblast process of adhesion, proliferation and differentiation. We examine a series of polymers and protein adhesions with which to functionalize the structures, and cell‐seeding methods, with a view to defining the optimal protocol for engineering skeletal muscle tissue. All polymer samples were tested for their mechanical and biological properties, to support the validity of our results in the real context of muscle tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
100.