A pathologic fracture of an intracortical chondroma masking as an osteoid osteoma

The differential diagnosis of a tibial intracortical diaphyseal lesion includes osteoid osteoma, periosteal chondroma, nonossifying fibroma, osteofibrous dysplasia, and adamantinoma. While osteoid osteomas represent 5% of all primary bone tumors, little is understood about intracortical chondromas. Intracortical chondroma was first described in 1990 and 7 reported cases have since been published. This article presents the first reported case of a pathologic fracture of an intracortical lesion in a child that shared radiographic and clinical features similar to those of osteoid osteoma, but on histopathologic examination revealed an intracortical chondroma. Our patient exhibited radiographic features of a poorly circumscribed cortical bone sclerosis, a centralized radiolucent nidus on computed tomography, and a hot bone scan of a lesion <1 cm in size that was consistent with an osteoid osteoma. An excision of the bone lesion was performed. The histopathology of the lesion revealed nodules of benign hyaline cartilage in cortical bone, consistent with an intracortical chondroma. Demarcated by cortical bone with mature Haversian systems rather than periosteum or cancellous bone, intracortical chondroma differs from the other 2 chondroma variants, periosteal chondroma and enchondroma, by its relationship to the surrounding bone. Enchondromas are characteristically understood to be asymptomatic. Intracortical chondromas along with periosteal chondromas have been found to present as painful lesions. The similarities with osteoid osteoma and intracortical chondroma in our patient make it circumspect in regards to ablating lesions (ie, needle radiofrequency ablation) without acquiring a biopsy in pediatric patients that both clinically and radiographically are presumably an osteoid osteoma.     

Mouse model of relapse to the abuse of drugs: procedural considerations and characterizations

To identify genetic risk factors involved in relapse to the abuse of drugs in humans, it is essential for researchers to develop a reliable mouse model of relapse by extending well-established extinction-reinstatement procedures in rats. Because of technical difficulties such as the relatively short duration of catheter patency in mice, few reports are available on the characterization of extinction-reinstatement behavior in wild-type and genetically engineered mutant mice. In this review, efforts are made to describe practical considerations during the establishment of extinction-reinstatement procedure in mice, including drug-primed, cue-induced, and stress-triggered reinstatement of previously extinguished drug-seeking behavior. Next, attention will be given to some characteristics of extinction-reinstatement behavior in mice. The present review might provide a new impetus in the exploration of genetic risk factors involved in relapse to drug dependence/addiction in humans using extinction-reinstatement procedures in widely available mutant mice.     

Preimplantation genetic diagnosis for mitochondrial DNA disorders: ethical guidance for clinical practice

Although morally acceptable in theory, preimplantation genetic diagnosis (PGD) for mitochondrial DNA (mtDNA) disorders raises several ethical questions in clinical practice. This paper discusses the major conditions for good clinical practice. Our starting point is that PGD for mtDNA mutations should as far as possible be embedded in a scientific research protocol. For every clinical application of PGD for mtDNA disorders, it is not only important to avoid a ‘high risk of serious harm'' to the future child, but also to consider to what extent it would be possible, desirable and proportional to try to reduce the health risks and minimize harm. The first issue we discuss is oocyte sampling, which may point out whether PGD is feasible for a specific couple. The second issue is whether one blastomere represents the genetic composition of the embryo as a whole – and how this could (or should) be investigated. The third issue regards the cutoff points below which embryos are considered to be eligible for transfer. We scrutinize how to determine these cutoff points and how to use these cutoff points in clinical practice – for example, when parents ask to take more or less risks. The fourth issue regards the number of cycles that can (or should) justifiably be carried out to find the best possible embryo. Fifth, we discuss whether follow-up studies should be conducted, particularly the genetic testing of children born after IVF/PGD. Finally, we offer the main information that is required to obtain a truly informed consent.     

细菌潜生体相关的IBS大鼠模型建立的影响因素

目的研究细菌潜生体（CGC）相关的IBS大鼠模型建立的影响因素，以完善该模型的建立。方法采用二步刺激法建立IBS大鼠模型，先用不同浓度组的头孢呋辛钠刺激大鼠产生CGC，然后用辣椒液刺激。模型建成判定指标为CGC定植、粪便含水量和排便次数等。结果不同浓度组的头孢吠辛钠刺激大鼠，引起CGC的动态变化特点和定植率不一样。获得IBS大鼠雄性与雌性比例为1．5：1。结论CGC相关的IBS大鼠模型建立，头孢呋辛钠浓度组合对CGC动态变化特点和定植起关键作用，并且该动物模型建立有性别差异，对IBS的发病机制与性别差异研究有重要意义。     

The chronic cerebral effects of cannabis use. II. Psychological findings and conclusions

This paper examines the research evidence on the question of whether sustained use of marijuana may produce chronic cerebral impairment as measured by neuropsychological measures. Evidence from both American and cross-cultural studies suggests that marijuana probably does not produce chronic cerebral impairment, although subtle impairment cannot be ruled out. Several suggestions for new lines of research are discussed including prospective studies, effects of cannabis use on later aging processes, and true experimental studies.     

应用下胫腓钩板固定器治疗下胫腓联合分离伴腓骨骨折

目的 观察并总结采用自行研制的新型内固定器——下胫腓钩板固定器(Hook—plate fixation,HPF)治疗16例下胫腓联合分离伴腓骨骨折的初步临床疗效。方法 自2001年10月～2003年3月采用下胫腓钩板固定器治疗下胫腓联合分离伴腓骨骨折16例,根据应用改良Mazur评价标准对其术后疗效进行评定。结果 随访时间3～30个月,平均11个月。骨折愈合的时间为12～18周,16例中优良15例,可1例,优良率93％。结论 下胫腓钩板固定器生物力学性能最佳,也是治疗下胫腓联合分离伴腓骨下段骨折的最好内固定方式之一,但远期疗效有待于进一步观察。     

小儿肠套叠超声与X线平片诊断的对比研究

目的:探讨超声与X线平片在诊断小儿肠套叠中的价值.方法:总结分析行超声及X线平片检查并经手术或X线下空气灌肠确诊的肠套叠患儿63例,以及均行超声及X线检查其他原因的腹痛患儿40例,分析其超声及X线报告结果.结果:63例肠套叠中,B超确诊肠套叠61例,X线平片确诊小儿肠套叠38例,超声灵敏度、特异度均较高.结论:小儿肠套叠应首选B超检查.     

Human neural crest cells contribute to coat pigmentation in interspecies chimeras after in utero injection into mouse embryos

The neural crest (NC) represents multipotent cells that arise at the interphase between ectoderm and prospective epidermis of the neurulating embryo. The NC has major clinical relevance because it is involved in both inherited and acquired developmental abnormalities. The aim of this study was to establish an experimental platform that would allow for the integration of human NC cells (hNCCs) into the gastrulating mouse embryo. NCCs were derived from pluripotent mouse, rat, and human cells and microinjected into embryonic-day-8.5 embryos. To facilitate integration of the NCCs, we used recipient embryos that carried a c-Kit mutation (W^sh/W^sh), which leads to a loss of melanoblasts and thus eliminates competition from the endogenous host cells. The donor NCCs migrated along the dorsolateral migration routes in the recipient embryos. Postnatal mice derived from injected embryos displayed pigmented hair, demonstrating differentiation of the NCCs into functional melanocytes. Although the contribution of human cells to pigmentation in the host was lower than that of mouse or rat donor cells, our results indicate that hNCCs, injected in utero, can integrate into the embryo and form mature functional cells in the animal. This mouse–human chimeric platform allows for a new approach to study NC development and diseases.Genetically engineered mice have been highly informative in studying the developmental origin of many inherited diseases (1–3). However, mouse models often fail to reproduce the pathophysiology of human disorders due to interspecies divergence, such as metabolic differences between mouse and human (4), or differences in genetic background (5). To overcome some of the limitations of transgenic mouse models, transplantation of disease-relevant human cells into mice has been informative and is frequently used in cancer research. However, this approach is primarily restricted to the study of end-stage-disease cell types and provides only limited insight into tumor initiation and early progression of the disease under in vivo conditions, with the exception of the hematopoietic lineages, where human hematopoietic stem cells were found to successfully engraft into immune-deficient mice and provided a powerful approach for studying blood diseases (6).Somatic cell reprogramming provides patient-specific induced pluripotent stem cells (iPSCs) that carry all genetic alterations contributing to the disease pathophysiology and thus allows for generating the disease-relevant cell types in culture (7). However, many complex diseases involve progressive cellular or genetic alterations that occur before the manifestation of a clinical phenotype. Therefore, it is not clear whether a disease-relevant phenotype can be observed in short-term cultures of cells derived from patients with long-latency diseases, such as Parkinson''s or Alzheimer’s disease or cancers like melanoma. A major challenge is establishing model systems that, using human embryonic stem cells (hESCs) or hiPSCs, will allow for the investigation of human disease under appropriate in vivo conditions.Transplantation of hiPSCs or hiPSC-derived cells into mouse embryos would present an attractive solution to many of the aforementioned limitations. The main advantage of such an approach is that the transplanted cells would integrate into the embryo and participate in normal embryonic development, and consequently could be studied over the lifetime of the mouse. Currently, it is controversial whether the injection of hESCs/hiPSCs into preimplantation mouse blastocysts can generate even low-grade chimeric embryos (8–11). As an alternative approach, we explored whether multipotent somatic cells would be able to functionally integrate into postgastrulation mouse embryos and allow for the generation of mouse–human chimeras. We investigated the potential of human neural crest cells (hNCCs), derived from hESCs/hiPSCs, to integrate into the mouse embryo and contribute to the NC-associated melanocyte lineage. The NC, a multipotent cell population, arises at the boundary between the neuroepithelium and the prospective epidermis of the developing embryo. Trunk NCCs migrate over long distances, with the lateral migrating NCCs generating all of the melanocytic cells of the animal’s skin (12).NCC migration, development, and differentiation into various tissues have been studied in vivo by generating quail–chick NC chimeras. In this model, donor quail tissues were grafted into similar regions of developing chicken embryos (13). The experimental approach of our present study was based on the generation of mouse–mouse NC chimeras that had been created by injection of primary mouse NCCs into the amniotic cavity of embryonic-day (E) 8.5 embryos (14, 15). The donor mouse NCCs (mNCCs), having been placed outside of the embryo, enter into the neural tube, presumably through the still-open neural pores, and transverse the epidermis. The donor mNCCs used in this previous study were collected from pigmented C57BL/6 mice, whereas the host embryos were derived from BALB/c albino mice. Thus, contribution of the donor mNCCs to the host embryo could be determined by the presence of pigmentation in the coats of the injected mice. The injected primary mNCCs contributed to coat color formation in the head and hind limb regions only, but not in the midtrunk area, likely reflecting the entry point of the cells through the neural pores with the anterior–posterior movement of the cells being hindered by endogenous melanoblasts (15). Indeed, when embryos carrying the white-spotted c-Kit mutation (W^sh/W^sh), which lack melanoblasts, were used as a host, extensive coat color contribution revealing anterior–posterior cell migration was observed, presumably because the donor NCCs could spread into the empty niches (14).Here, we differentiated mouse, rat, and human ESCs or iPSCs into NCCs that were injected in utero into E8.5 albino wild-type and c-Kit–mutant W^sh/W^sh embryos. Both the mouse and human NCCs migrated laterally under the epidermis and ventrally into deeper regions of the embryo. Importantly, analysis of postnatal animals derived from mouse, rat, or human NCC-injected embryos displayed coat color pigmentation from the donor cells. Our results demonstrate that NCCs from different species can integrate into the developing mouse embryo, migrate through the dermis, and differentiate into functional pigment cells in postnatal mice. The generation of postnatal mouse–human chimeras carrying differentiated and functional human cells allows for a novel experimental system in which to study human diseases in an in vivo, developmentally relevant environment.