Occipital foramina development involves localised regulation of mesenchyme proliferation and is independent of apoptosis

Cranial foramina are holes within the skull, formed during development, allowing entry and exit of blood vessels and nerves. Once formed they must remain open, due to the vital structures they contain, i.e. optic nerves, jugular vein, carotid artery, and other cranial nerves and blood vessels. Understanding cranial foramina development is essential as cranial malformations lead to the stenosis or complete closure of these structures, resulting in blindness, deafness, facial paralysis, raised intracranial pressure and lethality. Here we focus on describing early events in the formation of the jugular, carotid and hypoglossal cranial foramina that form in the mesoderm‐derived, endochondral occipital bones at the base of the embryonic chick skull. Whole‐mount skeletal staining of skulls indicates the appearance of these foramina from HH32/D7.5 onwards. Haematoxylin & eosin staining of sections shows that the intimately associated mesenchyme, neighbouring the contents of these cranial foramina, is initially very dense and gradually becomes sparser as development proceeds. Histological examination also revealed that these foramina initially contain relatively large‐diameter nerves, which later become refined, and are closely associated with the blood vessel, which they also innervate within the confines of the foramina. Interestingly cranial foramina in the base of the skull contain blood vessels lacking smooth muscle actin, which suggests these blood vessels belong to glomus body structures within the foramina. The blood vessel shape also appears to dictate the overall shape of the resulting foramina. We initially hypothesised that cranial foramina development could involve targeted proliferation and local apoptosis to cause ‘mesenchymal clearing’ and the creation of cavities in a mechanism similar to joint cavitation. We find that this is not the case, and propose that a mechanism reliant upon local nerve/blood vessel‐derived restriction of ossification may contribute to foramina formation during cranial development.     

Cutaneous lymphoblastic lymphoma with pre-B markers

Two children with cutaneous convoluted lymphoblastic lymphoma are reported. Malignant cells from both patients contained cytoplasmic Mu heavy chains characteristic of pre-B-cells and expressed CALLA and la antigens as well. Most cases of convoluted lymphoblastic lymphoma are T- cell-derived neoplasms. The non-T, non-B phenotype found in these two children demonstrates that histology does not necessarily predict immunophenotype. The association of the pre-B phenotype with cutaneous lymphoma has not been previously reported, but may represent a unique clinical-histopathologic-immunologic entity that occurs in young children.     

Early migration of tibial components is associated with late revision: A systematic review and meta-analysis of 21,000 knee arthroplasties

Purpose

We performed two parallel systematic reviews and meta-analyses to determine the association between early migration of tibial components and late aseptic revision.

Methods

One review comprised early migration data from radiostereometric analysis (RSA) studies, while the other focused on revision rates for aseptic loosening from long-term survival studies. Thresholds for acceptable and unacceptable migration were determined according to that of several national joint registries: < 5% revision at 10 years.

Results

Following an elaborate literature search, 50 studies (involving 847 total knee prostheses (TKPs)) were included in the RSA review and 56 studies (20,599 TKPs) were included in the survival review. The results showed that for every mm increase in migration there was an 8% increase in revision rate, which remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. Consequently, migration up to 0.5 mm was considered acceptable during the first postoperative year, while migration of 1.6 mm or more was unacceptable. TKPs with migration of between 0.5 and 1.6 mm were considered to be at risk of having revision rates higher than 5% at 10 years.

Interpretation

There was a clinically relevant association between early migration of TKPs and late revision for loosening. The proposed migration thresholds can be implemented in a phased, evidence-based introduction of new types of knee prostheses, since they allow early detection of high-risk TKPs while exposing only a small number of patients.Worldwide, several hundred thousand total knee prostheses (TKPs) are implanted each year and this number is expected to increase by a factor of 6 within the next 2 decades (Kurtz et al. 2005, 2007). Most of the new TKP designs have been introduced to the market without being shown to be safe or effective (Sheth et al. 2009). This has resulted in the widespread use of TKPs with failure rates exceeding 10 times the standard of national joint registries (< 5% failures at 10-year follow-up), such as the Accord, St Leger, and Journey-Deuce (Norton et al. 2002, Gilbert et al. 2009, Sheth et al. 2009, Palumbo et al. 2011 (personal communication)). To guarantee patient safety, several countries have developed guidelines, e.g. the NICE guidelines for total hip prostheses (2003). Furthermore, it has become increasingly evident that a phased, evidence-based introduction, as is common for pharmaceuticals, is needed to regulate the introduction of new TKPs to the market (Malchau 2000, McCulloch et al. 2009, Schemitsch et al. 2010). This should include systematic assessment and early detection of the major cause of TKP failure, which is aseptic loosening of the tibial component necessitating revision surgery (2003, AJR 2010).Although it can take 10 years before loosening causes symptoms, it is possible to detect loosening early postoperatively using radiostereometric analysis (RSA) (Selvik 1989, Grewal et al. 1992, Karrholm et al. 1994, Ryd et al. 1995). Since RSA allows in vivo, 3D measurement of the migration of TKPs with an accuracy of 0.2 mm for translations and 0.5 degrees for rotations, only a small number of patients need be exposed to potentially unsafe TKPs (Grewal et al. 1992, Ryd et al. 1995, Nelissen et al. 1998). RSA could therefore play an important role in the phased, evidence-based introduction of new TKPs (Selvik 1989, Karrholm et al. 1994, Ryd et al. 1995). However, the evidence for the relationship between early migration and TKP revision for aseptic loosening is limited to a few studies from the 1990s (Grewal et al. 1992, Ryd et al. 1995). Furthermore, the applicability of these studies is restricted, because surgical technique, fixation methods, implant design, and polyethylene have evolved since their publication.We hypothesized that early migration of the tibial component, measured through RSA, is associated with late revision for aseptic loosening of TKPs. We therefore systematically reviewed the association between early migration and late aseptic revision for the tibial component in TKPs. This could ultimately lead to clinical guidelines to be used in a phased introduction of new TKPs.     

胶原诱导性关节炎的评定与T细胞受体-热休克蛋白70DNA疫苗的保护作用

目的:纯化制备含有编码T细胞受体(TCR)Vβ5.2/8.2基因片段与结核杆菌热休克蛋白(HSP)70的一段保守序列P111-125的嵌合DNA疫苗,观察其对胶原诱导性关节炎的保护性作用。方法:实验于2006-07/2007-02在首都医科大学免疫学系实验室完成。①实验分组:36只Lewis大鼠随机分为6组,即正常对照组、胶原诱导性关节炎对照组、空质粒组、pTARGET-TCRVβ5.2-HSP70重组质粒治疗组、pTARGET-TCRVβ8.2-HSP70重组质粒治疗组及pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70重组质粒联合治疗组,每组6只。②实验方法:大量纯化制备重组DNA疫苗pTARGET-TCRVβ5.2-HSP70、pTARGET-TCRVβ8.2-HSP70和空质粒pTARGET,观察重组DNA疫苗对胶原诱导性关节炎的保护效果,包括关节炎指数评分、Eli-spot法测定脾细胞分泌的干扰素γ和白细胞介素4的水平、ELISA法测定血清中抗Ⅱ型胶原抗体的水平;光镜下观察大鼠后肢足关节的病理学变化。结果:36只Lewis大鼠均进入结果分析。重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70对胶原诱导性关节炎有较好的保护性作用,与胶原诱导性关节炎对照组相比,关节炎指数(P<0.05)下降,炎性细胞因子干扰素γ水平(P<0.05)和抗Ⅱ型胶原抗体水平(P<0.01)降低,抑制性细胞因子白细胞介素4水平(P<0.05)升高,病理学改变较轻。且两种重组质粒联合治疗的效果要比单种质粒好。结论:重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70能明显减轻胶原诱导性关节炎大鼠的关节炎症状和病理改变,二者联合应用效果更佳。     

Calcium Hydroxylapatite: Over a Decade of Clinical Experience

Background: Calcium hydroxylapatite is one of the most well-studied dermal fillers worldwide and has been extensively used for the correction of moderate-to-severe facial lines and folds and to replenish lost volume. Objectives: To mark the milestone of 10 years of use in the aesthetic field, this review will consider the evolution of calcium hydroxylapatite in aesthetic medicine, provide a detailed injection protocol for a global facial approach, and examine how the unique properties of calcium hydroxylapatite provide it with an important place in today’s market. Methods: This article is an up-to-date review of calcium hydroxylapatite in aesthetic medicine along with procedures for its use, including a detailed injection protocol for a global facial approach by three expert injectors. Conclusion: Calcium hydroxylapatite is a very effective agent for many areas of facial soft tissue augmentation and is associated with a high and well-established safety profile. Calcium hydroxylapatite combines high elasticity and viscosity with an ability to induce long-term collagen formation making it an ideal agent for a global facial approach.Aesthetic medicine has advanced greatly in the past decade in terms of our understanding of facial anatomy; the cumulative effects of the aging process; and how dermal fillers may be used to repair, reduce, and even reverse these changes. Initially, aesthetic practitioners were “chasing lines and wrinkles,” based on experience with bovine collagen injections beginning in the early 1980s. We now appreciate that a natural and more youthful appearance is dependent on reversing the cumulative effect of age-related changes both on the surface and in the subsurface tissues. For surface aging, restoration of textural and pigmentary alterations is of paramount importance; for the subsurface, restoring lost volume and shape is the key to the more youthful proportions desired by our patients. This focus on facial shape and volume to restore balance, symmetry, and the proportions of youth has led to the development and worldwide clinical use of an ever-expanding list of dermal fillers for treatment of facial aging.Dermal fillers as a category of implantable medical devices, consist of a wide array of products that differ significantly in their chemical composition, mechanism of action, duration, safety, and interaction with host tissues. Many different methods of categorization have been proposed, based in part on these differing characteristics; however, no single, universally agreed upon system exists to date. Of the proposed classification systems, one based on primary mechanism of action (MOA) first proposed by Werschler and Narurkar has been widely used.1 In this approach, dermal fillers are placed into categories of either collagen biostimulation or replacement volume as a primary MOA.In this schema, Radiesse® (calcium hydroxylapatite; CaHA, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a unique product because it provides both replacement volume and collagen biostimulation as a primary MOA. In addition, CaHA is biodegradable and reabsorbed naturally by the host’s metabolic processes. This biostimulatory MOA, with ultimate reabsorption, results in a performance profile that is unique to Radiesse.CaHA is a highly effective agent for many areas of facial soft-tissue augmentation and is associated with a well-established safety profile.2 The year 2013 marked a decade of Radiesse technology, which first received EU approval in 2003 for plastic and reconstructive surgery, including deep dermal and subdermal soft tissue augmentation of the facial area. In the intervening years, the range of uses for CaHA has evolved alongside developments in the field of aesthetic medicine from a surface-oriented two-dimensional approach, concentrating on removal of facial lines and folds, to a three-dimensional approach that also addresses both soft and hard tissue volume loss in both the face and the hands.3With the popularity of dermal fillers demonstrated by increasing numbers of treated patients, public awareness and acceptance of nonsurgical enhancement has greatly increased the treatment options available. Along with botulinum toxin injections and energy-based devices, fillers are the mainstay of most medical aesthetic clinics. With increasing patient demand and the increased availability of aesthetic providers, private practices have become more competitive. Patient retention is now a major objective of most aesthetic businesses. Patient satisfaction is a key element for patient retention and requires a portfolio of safe and effective products. Long-term clinical experience, clinical research, peer-reviewed publications and regulatory approvals have combined to demonstrate the safety and efficacy of CaHA. The product has been evolved to meet the demands of a continuum of aesthetic care in terms of enhancement of youthful patients (ages 25-35); early prevention, rejuvenation, and volume restoration for patients in the middle decades of life (35-55); and for the delay and maintenance as part of restoration for mature (55-75+) patients as well.In this tenth anniversary year, the authors consider the historical milestones of CaHA in aesthetic medicine, propose a protocol for a global facial approach using CaHA, and look at how its unique properties provide it with a place in today’s market and keep it at the forefront of modern aesthetic treatments. Throughout this publication, reference is made to labeled and off-label indications, techniques, and dilution protocols performed by experts in the field of aesthetic medicine. The reader is reminded that some of these are not approved by regulatory authorities and are not endorsed by Merz Pharmaceuticals GmbH.     

Social, emotional, and behavioral functioning of children with cancer

OBJECTIVE: It was hypothesized that children with cancer would have more social problems and difficulties with emotional well-being than case control, same race/gender, similarly aged classmates. STUDY DESIGN: Using a case controlled design, children with any type of cancer requiring chemotherapy except brain tumors (n = 76), currently receiving chemotherapy, ages 8 to 15, were compared with case control classroom peers (n = 76). Peer relationships, emotional well-being, and behavior were evaluated based on peer, teacher, parent, and self-report, and were compared using analysis of variance and structural equation modeling. RESULTS: Relative to case controls, children with cancer were perceived by teachers as being more sociable; by teachers and peers as being less aggressive; and by peers as having greater social acceptance. Measures of depression, anxiety, loneliness, and self-concept showed no significant differences, except children with cancer reported significantly lower satisfaction with current athletic competence. There were also no significant differences in mother or father perceptions of behavioral problems, emotional well-being, or social functioning. Scores on all standardized measures were in the normal range for both groups. Comparisons of the correlation matrices of children with cancer and to the correlation matrix of the comparison children using structural equation modeling suggested they were not significantly different. CONCLUSIONS: Children with cancer currently receiving chemotherapy were remarkably similar to case controls on measures of emotional well-being and better on several dimensions of social functioning. These findings are not supportive of disability/stress models of childhood chronic illness and suggest considerable psychologic hardiness.     

Comparison of health‐related quality of life and emotional distress among Chinese cancer survivors

The purpose of this study is to compare health‐related quality of life (HRQoL) and emotional distress among diverse cancer survivors who had completed all treatment within the previous year. A convenience sample of 353 cancers survivors (lung, head and neck, breast and prostate cancers) were recruited to complete a survey, which consisted of (i) Hospital Anxiety and Depression Scales; (ii) Chinese version of the Functional Assessment of Cancer Therapy—General version; and (iii) demographic and clinical data. The HRQoL scores were similar among the four types of survivors. Mild anxiety and depression levels were reported, but no significant difference was noted. Younger females with financial burdens and uncertain prognosis were particularly associated with HRQoL and emotional distress. Further studies are essential to identify specific problems that cancer patients experience after cancer diagnosis that might lead to the early detection of those most at risk of ongoing problems.