The consequences of risk reducing salpingo-oophorectomy: the case for a coordinated approach to long-term follow up post surgical menopause

Women with germline mutations in BRCA1 and BRCA2 genes have significantly increased lifetime risks of breast and ovarian cancer. To manage both the ovarian and breast cancer risks the current recommendation is undergo a risk reducing salpingo-oophorectomy (RRSO) prior to natural menopause. To date, studies have focussed on quality of life and sexual dysfunction in women who undergo RRSO, but few have reported on the wider physical consequences. We performed a questionnaire study in women with BRCA 1 or 2 gene mutations known to the Peter MacCallum Familial Cancer Centre. We gathered information about ovarian surgery, ongoing follow-up, management of risk factors including osteoporosis, and current severity of menopausal symptoms. Two hundred and nineteen women were surveyed. One hundred and forty-three of 157 responding participants (91?%) reported having RRSO. Sixty one were pre-menopausal at RRSO. Post surgical follow-up rates were generally low, and a minority of women reported recent bone density imaging or pharmaceutical prevention or treatment of osteoporosis. Menopausal symptoms appeared generally mild. No significant differences in symptom severity were observed in women who underwent a pre-menopausal RRSO compared to RRSO after natural menopause. These data indicate that a formalised follow-up protocol is necessary to optimally manage the consequences of a RRSO.     

Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

整形外科研究的循证医学证据水平

目的 近年来,医学、外科类文献有向循证医学方向发展的趋势.本研究旨在检测已发表的整形外科类文章的证据水平.方法 回顾性分析<整形再造外科杂志(Plastic and Reconstructive Surgery,PRS)><整形外科年鉴(Annals of Plastic Surgery,Annals)><整形再造与美容外科杂志(Journal of Plastic,Reconstructive,and Aesthetic Surgery,JPRAS)><美国美容外科杂志(American Journal of Aesthetic Surgery,Aesthetic)>4本主要的整形外科类杂志2009年1～12月刊载论文利用证据的水平.结果 在1759篇文献中,共有726篇(41%)纳入本研究标准(排除动物实验、尸体研究、基础医学、文献复习、继续教育和信函等方面文献).将选中的文献根据其证据水平进行分级(Ⅰ～Ⅳ级;Ⅰ级,证据水平最高,如随机对照研究;Ⅳ级,证据水平最低,如病例报告).4本杂志的平均证据水平分别为:PRS=3.05,Aesthetic=3.11,JPRAS=3.35,Annals=3.31.4本杂志的平均证据水平,除了JPRAS与Aesthetic的差异无统计学意义外,余者差异均有统计学意义(P<0.05).本研究纳入标准的文献,只有2.2%的证据水平为Ⅰ级.结论 4本杂志的平均证据水平为3.2(Ⅲ级水平).为了使整形外科专业加入到高水平循证医学行列,我们应当在今后的工作中着重强调随机对照研究的应用.     

The Effect of Total Knee Arthroplasty on Knee Joint Kinematics and Kinetics During Gait

This study determined how total knee arthroplasty (TKA) altered knee motion and loading during gait. Three-dimensional kinematic and kinetic gait patterns of 42 patients with severe knee osteoarthritis were collected 1 week prior and 1-year post-TKA. Principal component analysis extracted major patterns of variability in the gait waveforms. Overall and midstance knee adduction moment magnitude decreased. Overall knee flexion angle magnitude increased due to an increase during swing. Increases in the early stance knee flexion moment and late stance knee extension moment were found, indicating improved impact attenuation and function. A decrease in the early stance knee external rotation moment indicated alteration in the typical rotation mechanism. Most changes moved toward an asymptomatic pattern and would be considered improvements in motion, function, and loading.     

Human myoblast engraftment is improved in laminin-enriched microenvironment

BACKGROUND: One major challenge in developing cell therapy for muscle diseases is to define the best condition for the recipient's muscle to niche donor cells. We have examined the efficiency of human myoblast transplantation in an immunodeficient animal model, after local irradiation, as well as the potential impact of laminin on myoblast behavior. METHODS: Human myoblasts were injected into preirradiated tibialis anterior muscles from immunodeficient mice. The donor cell engraftment, proliferation, and laminin content within the transplanted muscles were evaluated by immunocytochemistry. Additionally, the effect of laminin upon myoblast proliferation, migration, and survival was ascertained in vitro. RESULTS: Engraftment of human myoblasts into the skeletal muscle of immunodeficient Rag2-/gammac-/C5- mice presubjected to local irradiation provided the best niche for myoblast engraftment, as demonstrated by the number of viable and proliferating donor cells found in the host muscle. Local irradiation significantly enhanced laminin deposition within the recipient's muscle and donor cells were preferentially located in laminin-enriched areas. The same batch of myoblasts used for in vivo injections also responded to laminin in vitro with increased proliferation and cell survival, as well as an improved migratory response. CONCLUSIONS: We show that local irradiation enhances the laminin content in the host muscle microenvironment and provides a better engraftment of human myoblasts. In addition, laminin increases myoblast proliferation, survival, and migration in vitro. These data provide combined in vivo and in vitro evidence that laminin status should be taken into account when designing experimental and clinical cell therapy strategies for muscle disease.     

Kinematic and temporal interactions of the lumbar spine and hip during trunk extension in healthy male subjects

Kinematic properties of trunk extension are considered sensitive differentiators of movement between asymptomatic and low back pain subjects. The aim of this study was to quantify the continuous interaction of the hip and lumbar spine kinematics and temporal characteristics as a function of direction during the task of trunk bending backwards and returning to the upright position in healthy young subjects. The sagittal hip and lumbar spine kinematics during the extension task were examined in 18 healthy male subjects. Five trials of trunk extension were recorded for each subject and paired t-tests were then used to determine significant differences (P < 0.05) between the mean lumbar and the hip time-normalized kinematic and temporal variables. The data from the full cycle of trunk extension was analyzed with respect to movement initiation, time to reach peak velocity and peak angular displacement during the full cycle of trunk extension. Three distinct phases of movements were identified based on the continuous movement trajectories of velocity and angular displacement in the lumbar spine and hip; that of extension, return and, a terminal overcorrection phase. There were significant differences identified in the respective mean peak angular velocities of the lumbar spine (21.7 +/- 8.6, 37.0 +/- 14.7, 8.3 +/- 5.0 deg/s) when compared with those of hip (14.6 +/- 6.1, 21.7 +/- 8.5, 5.4 +/- 3.5 deg/s) in each of these three phases. The lumbar spine initiated the movement of trunk extension when bending backwards and returning to the upright position significantly early than that of the hip. These results highlight that in normal healthy adults there is the tendency for the lumbar spine to dominate over the hip during the task of backward trunk bending in terms of the amount and velocity of movement. At the end of extension the kinematics of the lumbar spine and hip kinematic are characterized by a terminal overcorrection phase marking the completion of the movement.     

Consensus guidelines for sustained neuromuscular blockade in critically ill children

BACKGROUND: The United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group is a multidisciplinary expert panel created to produce consensus guidelines on sedation, analgesia and neuromuscular blockade in critically ill children and forward knowledge in these areas. Neuromuscular blockade is recognized as an important element in the care of the critically ill and adult clinical practice guidelines in this area have been available for several years. However, similar clinical practice guidelines have not previously been produced for the critically ill pediatric patient. METHODS: A modified Delphi technique was employed to allow the Working Group to anonymously consider draft recommendations in up to three Delphi rounds with predetermined levels of agreement. This process was supported by a total of four consensus conferences and once consensus had been achieved, a systematic review of the available literature was carried out. RESULTS: A set of consensus guidelines was produced including six key recommendations. An evaluation of the existing literature supporting these recommendations is provided. CONCLUSIONS: Multidisciplinary consensus guidelines for maintenance neuromuscular blockade in critically ill children (excluding neonates) have been successfully produced and are supported by levels of evidence. The Working Group has highlighted the paucity of high quality evidence in these important clinical areas and this emphasizes the need for further randomized clinical trials in this area.     

Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery

BACKGROUND: Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle. METHODS: On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed. RESULTS: Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle. CONCLUSION: Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction.