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1.
Apoptosis and its clinical impact   总被引:8,自引:0,他引:8  
Gastman BR 《Head & neck》2001,23(5):409-425
BACKGROUND: Apoptosis or programmed cell death is an orderly cascade that can be regulated and ultimately results in the demise of the cell. Induction of apoptosis can occur by various chemical and biologic agents. Initiation of apoptosis leads to activation of effector molecules particularly caspases. These proteases cleave distinct protein substrates, resulting in the morphologic changes seen in apoptosis. This form of cell death is involved in almost every physiologic and pathogenic process in the body. For this reason the ability to control apoptosis has important therapeutic ramifications. RESULTS: This article reviews the history of the investigation of apoptosis and summarizes the most important pathways and regulatory molecules involved in this process. The major regulators of apoptosis, including the Bcl-2, caspase, and inhibitor of apoptosis families, are examined. The two major apoptotic pathways, including the extrinsic/cell surface death receptor and the intrinsic/mitochondrial pathways, are discussed. A major emphasis is given to examining the relationship between apoptosis and certain disease processes. This review specifically focuses on the importance of apoptosis research in the development of new methods of management of cancer with an emphasis in head and neck oncology. CONCLUSIONS: Apoptosis is a rapidly growing field. The understanding of the mechanisms and effector molecules controlling this form of cell death is evolving. On the basis of increasing knowledge of how programmed cell death is regulated and the improvements in designing and developing gene therapies and chemicals that are more accurate in targeting specific molecules, the control of apoptosis will become more important in the clinical setting. This possibility will open the door for new therapeutic endeavors in many areas of medicine and specifically in the area of oncology.  相似文献   

2.
Gaucher disease (GD) is a rare, genetic lysosomal disorder leading to lipid accumulation and dysfunction in multiple organs. Involvement of the skeleton is one of the most prevalent aspects of GD and a major cause of pain, disability, and reduced quality of life. Uniform recommendations for contemporary evaluation and management are needed. To develop practical clinical recommendations, an international group of experienced physicians conducted a comprehensive review of 20 years’ of the literature, defining terms according to pathophysiological understanding and pointing out best practice and unmet needs related to the skeletal features of this disorder. Abnormalities of bone modeling, reduced bone density, bone infarction, and plasma cell dyscrasias accompany the displacement of healthy adipocytes in adult marrow. Exposure to excess bioactive glycosphingolipids appears to affect hematopoiesis and the balance of osteoblast and osteoclast numbers and activity. Imbalance between bone formation and breakdown induces disordered trabecular and cortical bone modeling, cortical bone thinning, fragility fractures, and osteolytic lesions. Regular assessment of bone mineral density, marrow infiltration, the axial skeleton and searching for potential malignancy are recommended. MRI is valuable for monitoring skeletal involvement: It provides semiquantitative assessment of marrow infiltration and the degree of bone infarction. When MRI is not available, monitoring of painful acute bone crises and osteonecrosis by plain X-ray has limited value. In adult patients, we recommend DXA of the lumbar spine and left and right hips, with careful protocols designed to exclude focal disease; serial follow-up should be done using the same standardized instrument. Skeletal health may be improved by common measures, including adequate calcium and vitamin D and management of pain and orthopedic complications. Prompt initiation of specific therapy for GD is crucial to optimizing outcomes and preventing irreversible skeletal complications. Investing in safe, clinically useful, and better predictive methods for determining bone integrity and fracture risk remains a need. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.  相似文献   

3.
16-days old rats were operated with either uni- or bilateral ligation of ductuli efferents and separation of testis and epididymis to the level of the inferior epididymal artery (non-union operation), induction of cryptorchidism or bilateral sham operation. The epididymides were weighed and the epididymides and deferent ducts were examined with light- and electron-microscopy at days 30, 37, 44 and 58. Bilateral non-union operated epididymides and cryptepididymides had a significantly lower weight increase than controls, but the histology and diameter of epididymal tubules were unchanged. This indicates a true growth retardation and reduced length of epididymal tubules of non-union operated and cryptepididymides. For bilateral operations a positive correlation was found between the weight of epididymis and plasma levels of total testosterone as reported earlier. Unilaterally operated epididymides had a weight development significantly below contralateral controls, despite normal plasma levels of testosterone. It is concluded that the reduced-weight of unilaterally operated epididymides is the result of diminished local androgen stimulation from the ipsilateral testis. Non-union of testis and epididymis may have pathogenetic significance in maldescent of testis by a retarded growth of the ductal system.  相似文献   

4.
白细胞介素(IL)-37是近年发现的具有抑制炎症作用的IL-1家族细胞因子,共有a~e五种不同的亚型,其中IL-37b是目前研究的热点。最近研究发现,IL-37在骨关节炎性疾病的发生发展中对炎性因子和炎性介质的调节起着重要作用,但其具体调节机制尚不完全清楚。本文主要综述IL-37的生物学特征、信号通路及其在骨关节炎性疾病的研究现况,旨在为骨关节炎性疾病的发病机制、分型和诊断积累理论基础,为IL-37在骨关节炎性疾病的诊疗应用提供新思路。  相似文献   

5.
目的:探讨宫、腹腔镜联合诊治女性不孕症的效果.方法:回顾分析2005年5月至2010年4月80例女性不孕症患者采用宫、腹腔镜联合诊治的临床资料.结果:手术时间平均(55±17) min,术中出血量平均(80±13) ml.80例不孕症患者中,盆腔炎37例,子宫内膜异位症30例,多囊卵巢6例,盆腔结核3例,子宫肌瘤3例,...  相似文献   

6.
目的 探讨总结与显微外科相关的特殊组织器官离断再植的方法与经验.方法 对5例耳廓离断、1例颏部组织离断、1例头皮撕脱离断、1例阴茎完全离断、1例足部长组织块离断、1例足部五趾完全离断的组织器官进行显微再植,手术分别吻合了耳后动脉下耳支、面动脉颏支、双侧枕动脉和颞动脉、阴茎背动脉、足底内侧动脉和足底弓动脉、趾动脉和趾(跖)背动脉.结果 1例再植断耳失活,1例再植头皮失活,1例足部长组织块离断再植后部分足跟软组织坏死,予以皮瓣修复,其余再植组织及器官均成活.术后随访3~28个月,再植器官外观、感觉恢复良好,功能基本恢复.结论 完全离断的特殊组织或器官一般均可找到知名血管予以吻合,预防血管危象是成活关键,再植后外观满意、功能恢复良好.  相似文献   

7.
目的探索阿司匹林(aspirin,ASP)联合辛伐他汀(simvastatin,SIM)对成骨细胞增殖和分化的影响,为临床上两者联合使用的可行性提供细胞学基础。方法获取SD大鼠成骨细胞,随机分为对照组(CON)、ASP组、SIM组和ASP-SIM组等4组,培养基中分别添加安慰剂、ASP、SIM和ASP联合SIM干预,培养7 d后,通过MTT法检测细胞的增殖情况,碱性磷酸酶(alkaline phosphatase,ALP)及茜素红染色观察细胞的功能状态,蛋白电泳观察骨钙素(osteocalcin,OCN)及Runx2蛋白的表达情况。结果 ASP及SIM单独作用于成骨细胞时,都可以明显促进成骨细胞的增殖,增加ALP活性及矿化能力,同时明显促进OCN及Runx2蛋白的表达;联合使用效果明显优于单独使用,比较差异有统计学意义(P0.05)。结论 ASP及SIM都可以明显促进成骨细胞增殖和分化,且联合使用效果更佳。  相似文献   

8.
脊柱手术中TES-MEP和CSEP联合监测脊髓功能的作用评价   总被引:1,自引:0,他引:1  
目的 探讨脊柱手术中经颅电刺激运动诱发电位(TES-MEP)和皮层体感诱发电位(CSEP)联合监测脊髓功能的临床应用价值.方法 分析2006年7月至2009年4月脊柱手术中同时记录双侧胫前肌、足足母短屈肌(颈椎病变增加鱼际肌)TES-MEP和双侧胫后神经(颈椎病变增加尺神经)CSEP共293例患者的临床资料.术中全静脉麻醉维持,部分患者辅助使用小剂量七氟烷吸入或小剂量肌肉松弛药.将TES-MEP、CSEP、联合监测的结果与术后脊髓运动和感觉功能进行比较及相关分析.结果 术中TES-MEP、CSEP、联合监测的成功检出率分别为90.8%、96.9%和100%.术中TES-MEP、CSEP判断脊髓运动功能的灵敏度分别为100%和89.3%,特异度分别为98.4%和96.9%,约登指数分别为0.984和0.862;而判断脊髓感觉功能的灵敏度分别为76.7%和93.3%,特异度分别为98.7%和98.0%,约登指数分别为0.754和0.913;联合监测的灵敏度为100%,特异度96.9%,约登指数0.969.结论 TES-MEP监测脊髓运动功能的准确性高于CSEP,而CSEP监测脊髓感觉功能的准确性高于TES-MEP;联合监测对脊髓功能监测的灵敏度和准确性又高于单一的TES-MEP或CSEP监测,它是目前脊柱脊髓手术中较为理想的监测方法.  相似文献   

9.
This opinion review considers the prevailing question of whether to screen or not to screen for adolescent idiopathic scoliosis. New and improved standards of people-oriented care and person-centredness, as well as improved principles of preventive screening and guideline development, have been postulated and implemented in health care systems and cultures. Recommendations addressing screening for scoliosis differ substantially, in terms of their content, standards of development and screening principles. Some countries have discontinued issuing recommendations. In the last decade, a number of updated and new recommendations and statements have been released. Systematically developed guidelines and recommendations are confronted by consensus and opinion-based statements. The dilemmas and discrepancies prevail. The arguments concentrate on the issues of the need for early detection through screening in terms of the effectiveness of early treatment, on costs and cost-effectiveness issues, scientific and epidemiologic value of screenings, and the credibility of the sources of evidence. The problem matter is of global scale and applies to millions of people. It regards clinical and methodological dilemmas, but also the matter of vulnerable and fragile time of adolescence and, more generally, children's rights. The decisions need to integrate people's values and preferences – screening tests need to be acceptable to the population, and treatments need to be acceptable for patients. Therefore we present one more crucial, but underrepresented in the discussion, issue of understanding and implementation of the contemporary principles of person-centred care, standards of preventive screening, and guideline development, in the context of screening for scoliosis.  相似文献   

10.
Bioautography of human semen demonstrated the presence of L-carnitine, acetylcarnitine, propionylcarnitine and C4-acylcarnitines (butyrylcarnitines). In studies designed to ascertain the organs secreting these compounds into semen it was found that: Quantitative analyses of semen obtained pre- and post-vasectomy showed markedly decreased L-carnitine concentrations, slightly decreased acetylcarnitine levels, and unchanged propionyl- and butyrylcarnitine concentrations as a result of vasectomy. The earlier portion of human split ejaculate samples characteristically contained higher concentrations of carnitine and its propionyl- and butyryl esters and a lower concentration of acetylcarnitine than did the later portion. Vas deferens luminal fluid contained carnitine and each of the short-chain acyl derivatives, as shown by bioautography. Prostatic fluid contained only small amounts of carnitine and its derivatives. Spermatozoa contained much more acetylcarnitine than free carnitine, and only trace amounts of the other acylcarnitines. It is concluded that carnitine in semen is secreted primarily by the epididymis, that a proportion of the acetylcarnitine derives from the seminal vesicles and epididymis, and that propionylcarnitine and butytylcarnitine enter semen, at least in part, together with the vas deferens contents.  相似文献   

11.
澳大利亚的移植医学水平位于国际前列,也面临着供器官短缺的问题。为了扩大供器官来源,提高利用率,从2008年开始,澳大利亚政府开始着手建立其国内统一的、公平公正的组织器官捐献、分配和移植体系。本文着重从澳大利亚组织器官捐献和移植的管理机构、尸体供器官的分配原则和移植受者选择标准以及供者选择原则等方面对该体系进行介绍。  相似文献   

12.
Reports linking long‐term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross‐linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long‐term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. © 2010 American Society for Bone and Mineral Research.  相似文献   

13.
The treatment of prostate cancer has undergone a fundamental change in the last decade. New surgical and nonsurgical minimal invasive methods have evolved. As the methodology of the different treatments is commonly known to urologists, this article focuses on oncological and functional outcome of open retropubic (ORP), trans- or extraperitoneal endoscopical (LRP), and robot-assisted radical prostatectomy (RALP), based on personal experience and review of the literature. A MEDLINE search was performed to review the literature on LRP and RALP between 1982 and 2007 with special emphasis on oncological and functional results, technical considerations, comparison of LRP and RALP to ORP, laparoscopic training, historical aspects, and cost-efficiency of the techniques. Based on diligent training and proctoring programs, a continuous dissemination of laparoscopic techniques takes place. There is a trend towards the extraperitoneal access in most of the minimal invasive programs at least in the European community. Mid-term outcomes of LRP and short-term outcomes of RALP achieved equivalence to open surgery with regards to complications, oncologic and functional results. Distinct advantages of LRP include less postoperative pain, lower transfusion rates, shorter convalescence, and better cosmetics. In contrast to RALP, LRP reaches cost-equivalence with open surgery in selected centers. LRP and RALP reproduce the short-term results of open surgery while providing the advantages of a minimal access. Video-assisted teaching improves the transfer of anatomical knowledge and technical knowhow, but the discussion about the longer learning curve for laparoscopy handling remains. The future will show if European centers adopt the use of robots comparable to the United States. T. R. Herrmann and R. Rabenalt contributed equally to this article.  相似文献   

14.
目的 观察和探讨2型糖尿病大鼠血清及生殖器官中各指标含量的变化和相互关系,及其对雄性大鼠生殖器官的影响。方法 雄性Wistar大鼠30只,其中20只制备2型糖尿病模型,余为对照组。实验结束时,观察组织的病理改变,并测定各指标的变化。结果 2型糖尿病大鼠模型制备成功;与对照鼠比较:电镜显示睾丸精原细胞线粒体呈空泡样变;附睾管腔内精子数量减少或缺如。光镜下见阴茎海绵体平滑肌数量减少,纤维结缔组织增生。NO含量和NOS活性均显著低于对照组,ET浓度明显高于对照组。血清、阴茎中CGRP含量均低于对照组,但睾丸、附睾中CGRP含量与对照组比较无显著差异。睾丸中ET与CGRP含量、ET与NO含量呈负相关。结论 2型糖尿病时大鼠生殖器官均受到不同程度的损害;糖尿病时上述指标的变化结果可能是导致其功能紊乱,进而造成不育症的原因。  相似文献   

15.
Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 μg kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6 hours after infusion of endotoxin or saline. Serum Cortisol and interleukin–lβ were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 μg kg-1 BW. Following infusion of endotoxin, the number of granulocytes in peripheral blood decreased from 2.44 to 0.064 times 10 1-1 two hours later. Within 5 min after infusion the overall oxidative burst of the peripheral blood granulocytes was increased and the granularity had decreased. Serum Cortisol and interleukin–lβ increased significantly. The radioactivity of labelled cells in the bone marrow and spleen decreased to 83.1% and 91.6% of initial values. At the same time there was a transient sequestration of labelled granulocytes in the lungs reaching 117.6% of initial values. The radioactivity of the liver increased continuously to 118.4%. The results indicate that endotoxin induces an efflux in activated granulocytes from peripheral blood, bone marrow and spleen to the lungs and liver. The sequestration of granulocytes may contribute to the development of ARDS and liver failure in sepsis.  相似文献   

16.
Objective: To study the anatomical and biomechanical features of sacral pedicle and lateral mass so as to provide reference for clinical screw fixation technology of sacral pedicle and lateral mass.Methods: A total of 60 adult patients' spiral CT images of the sacrum and coccyx were selected randomly. The entry points of sacral pedicle and lateral mass screws were determined, and the screw trajectory was measured using the three dimensional reconstruction method. Meanwhile,the gross anatomy was scrutinized in 15 adult cadaver specimens to determine the sacral pedicle and lateral mass screw entry points. The length, width and angle of sacral pedicle and lateral mass screw trajectory were measured. Eight of 15cadaver specimens were selected to test the maximal extraction force of sacral pedicle and lateral mass screws. The clinical data of 15 cases treated by pedicle and lateral mass screw technology were collected and analyzed.Results: The diameter and length of S1-S5 sacral pedicle and lateral mass screw trajectory were regular, with about 20° inclination angle. The S1 pedicle screw entry point was located at the intersection point of the basal lateral part of articular process and median line of transverse process, and no significant difference was found for the maximal extraction force between pedicle and lateral mass screws (P>0.05). The entry points of S2-S5 pedicle screws were located at the intersection point of the line connecting adjacent posterior sacral foramina and median line of the transverse process.The lateral mass screw entry point of S2-S5 was on the median side of intersection point between median line of the transverse process and lateral sacral crest. The maximal extraction force of pedicle screws was significantly greater than that of lateral mass screws (P<0.05).Conclusion: Both the sacral pedicle and the lateral mass screw fixation techniques can offer effective fixation and reconstruction for fracture of the sacrum and coccyx,but pedicle screw fixation may be more convenient, safe and reliable than lateral mass screw fixation.  相似文献   

17.
快速破坏性髋关节病(RDHD)是一种以髋关节,尤其是股骨头、股骨颈骨质迅速破坏从而导致髋关节功能迅速下降并伴有髋关节剧烈疼痛的疾病,人群发病率很低,60岁以上老年女性发病率相对较高。回顾性分析国内外相关研究文献,RDHD的疾病名称、定义及发病机制等均存在明显争议,较为常用的疾病名称为快速破坏性髋关节病,影像学以中晚期股骨头、股骨颈明显骨质破坏缺损为特征性表现,结合患者疾病病程可明确诊断,但早期影像学无有诊断价值表现,患者症状体征也不具有特异性,故而早期诊断困难。目前的研究认为其发病与患者的骨质疏松状态、髋关节生物力学改变及细胞、细胞因子活化等多种因素相关,但具体的生理病理过程暂未明确。RDHD治疗早中期以对症及抗骨质疏松治疗为主,全髋关节置换术可用于晚期功能受限患者的手术治疗,但术后假体松动的发病率较高。  相似文献   

18.
《Surgery (Oxford)》2022,40(1):62-69
Burns are a major cause of morbidity and mortality worldwide. Vulnerable people such as children, the frail and elderly, and the socially deprived are at particular risk. Most burns are caused by thermal injury to the skin, but electrical and chemical burns can be very severe. Fortunately, most burns are minor and superficial and can be managed by primary health care professionals. However, major and severe burns require in-hospital management from a team of surgeons and other specialists. Life-threatening conditions such as smoke inhalation airway damage and severe fluid loss should be addressed during the initial resuscitation. Prevention of further thermal damage by cooling is important along with prevention of secondary infection of burn injuries. A wide variety of dressings is available for the management of burns and expert nursing care is vital. Surgical intervention may be urgently required for fasciotomy or escharotomy in cases of compartment syndrome or circumferential burns, respectively. Debridement, skin grafting and reconstructive procedures will be required over the medium or long term for patients with severe or complex burns and should be planned with appropriate multidisciplinary expertize. The functional and psychological impact of major burn injury should not be underestimated.  相似文献   

19.
目的 通过比较糖皮质激素诱导骨质疏松模型大鼠(GIOP)在成模前后骨密度、病理组织以及瘦素(leptin)、血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白差异表达变化阐释糖皮质激素性骨质疏松的作用机制。方法 采取大腿内侧交替肌肉注射地塞米松注射液(DEX)建立骨质疏松症大鼠实验模型,连续注射8周,造模8周后处死各组大鼠,对右侧股骨胫骨进行骨密度检测、HE 染色,确定最佳造模剂量,继而通过免疫组织化学、蛋白免疫印迹的方法检测正常SHAM与DEX大鼠Leptin、VEGF蛋白的表达。结果 结合骨密度和HE染色的结果,确定DEX 2.5 mg/kg为地塞米松注射液诱导继发性骨质疏松的最佳造模剂量,免疫组织化学和蛋白免疫印迹检测发现,与SHAM组相比,DEX 2.5 mg/kg组大鼠Leptin、VEGF蛋白的表达均降低,差异有统计学意义(P<0.05)。结论 糖皮质激素诱导的骨质疏松是通过抑制Leptin、VEGF蛋白表达,抑制血管生成进而抑制成骨发挥作用的,据此推测Leptin、VEGF可能是糖皮质激素性骨质疏松发病的潜在作用靶点。  相似文献   

20.
《Renal failure》2013,35(1):110-117
The aim of this study is to test the glomerular and other quantitative parameters of kidneys of anencephalic fetuses and comparing those to “normal” fetuses. In this study, 20 kidneys of human fetuses (5 boys and 5 girls of anencephalic fetus, and 5 boys and 5 girls of normal fetus), at gestational ages of 25–30 weeks, were examined. This study is based on two basic research methods: one is a conventional anatomical measurement at the macroscopical level; the other is a design-biased stereological method at the microscopical level. Physical dissector and Cavalieri principle were used to estimate the total and numerical density of glomerulus and the volume of kidney, respectively. The results of the two types of investigation were compared based on anencephalic/normal and boy/girl kidneys at both the macroscopical and microscopical levels. There was no significant difference found between the quantitative features of kidneys (volume of kidneys and mean number and/or height of glomerulus) belonging to anencephalic and normal fetuses. The results of this study suggest that anencephalic fetuses did not differ from normal fetuses in respect of kidneys.  相似文献   

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