Idiopathic scoliosis: biomechanics and biology

For whatever reason, right-left asymmetry has attracted an illogical proportion of research effort. Non-structural scoliosis, for example secondary to a leg length inequality, is indeed a problem of right-left asymmetry, but structural scoliosis is a complex three-dimensional deformity involving all planes. Biomechanical, biological and clinical evidence indicates clearly that the problem is one of front-back asymmetry and not right-left. The importanc of biological factors lies in their ability to bring the spinal column to and beyond its buckling threshold. Thus a taller and more slender spine is more liable to bend and, being stiffer in the sagittal plane, favours movement into other planes. This epitomises the spine of the scoliosis patient who is growing faster with a spinal template similar to other family members allowing idiopathic scoliosis to express itself genetically. It is the opposite condition to idiopathic hyperkyphosis (Scheuermann's disease), but this deformity is rotationally stable, thus remaining in the sagittal plane. The presence of an adjacent area of lordo-scoliosis below the region of hyperkyphosis testifies to the common nature of the pathogenesis of idiopathic scoliosis and Scheuermann's disease. It is the area of compensatory hyperlordosis below the Scheuermann's area that has obligatorily buckled and represents a human model supporting the lordosis theory, as does surgically tethering the back of the young growing human spine, which crankshafts accelerated progression. Similarly the only successful animal model of the formation of idopathic follows creation of a lordotic spinal segment in an otherwise kyphotic spine. For centuries, engineers have recognised that the mechanical behaviour of a column under load is influenced by geometry, as well as by material properties; it is clear that the spinal column also obeys these well-described laws.     

The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds

White matter lesions on computed tomography of the head were studied in relation to neuropsychological functioning in subjects from a representative sample of non-demented ( n = 134) and demented ( n = 98) 85-year-olds. Non-demented subjects with white matter lesions ( n = 46) scored significantly lower in tests of verbal ability (Synonyms), spatial ability (Block Design, Clock Test), perceptual speed (Identical forms), secondary memory (Thurstone Picture Memory), basic arithmetic (Coin Test) and the global cognitive screening test Mini-Mental State Examination than non-demented subjects without white matter lesions ( n = 88). Demented subjects with white matter lesions ( n = 67) scored significantly lower in tests of spatial ability (Block Design and Clock Test) and secondary memory (free recall in the MIR memory test, Ten-word memory test I and II) and in the Mini-Mental State Examination than demented subjects without white matter lesions ( n = 31). It is concluded that white matter lesions contribute to cognitive decline in both non-demented and demented elderly subjects.     

Intrinsic Organization and Connectivity of Intrastriatal Striatal Transplants in Rats as Revealed by DARPP-32 Immunohistochemistry: Specificity of Connections with the Lesioned Host Brain

Intrastriatal grafts of tissue obtained from the striatal or neocortical primordia of rat fetuses have been studied with respect to their intrinsic organization and connectivity using antibodies to DARPP-32 in combination with acetylcholinesterase (AChE) histochemistry, tyrosine hydroxylase (TH) immunocytochemistry, and anterograde and retrograde axonal tracing techniques. The striatal grafts were characterized by distinct patches of DARPP-32-immunoreactive neurons, which were identical to the densely AChE-positive patches stained in adjacent sections from the same specimens. The non-patch areas possessed only few DARPP-32-positive neurons and contained only sparse AChE-positive fibres. The cortical grafts, by contrast, contained no neurons with clear-cut DARPP-32-positivity and they exhibited a sparse, evenly distributed AChE fibre network, similar to that seen in the non-patch areas of the striatal grafts. The host dopaminergic afferents, as revealed by TH immunostaining, had grown selectively into the DARPP-32-positive patches in the striatal grafts, where they formed a dense terminal network around the DARPP-32-positive cell bodies. The non-patch areas, as well as the cortical grafts, received only sparse TH innervation. By contrast, the host cortical afferents, labelled by Phaseolus vulgaris leucoagglutinin from the host frontal cortex, were seen to extend into both the patch and non-patch areas of the striatal grafts. Transplant neurons projecting into the host brain were labelled by Fluoro-Gold injections into the ipsilateral host globus pallidus. These injections labelled large numbers of medium-sized neurons within the striatal grafts and the vast majority of them (over 85%) were confined to the DARPP-32-positive patches. Similar Fluoro-Gold injections labelled only few graft neurons in the cortical grafts. The results indicate that the striatal grafts are composed of a mixture of striatal and non-striatal tissue, and that the striatal graft compartment selectively establishes afferent and efferent connections with the host nigro-pallidal system. These graft connections demonstrate a remarkable specificity in the formation of graft - host connectivity. The results, moreover, suggest that developmental properties of the grafted striatal primordium are retained and expressed in the implanted cell suspension, and that the neuronal systems of the lesioned adult host brain, at least to some extent, remain responsive to growth regulating mechanisms normally operating during ontogenetic development.     

鼻咽癌旁上皮细胞核DNA含量分析

应用显微分光光度计测定15例鼻咽癌19处癌旁病变的上皮细胞核DNA含量并与浸润癌相比较。中、重度异型增生上皮细胞核DI及超过2.5c细胞的百分数处于单纯增生+轻度异型增生与浸润癌之间,3组DI及超过2.5c细胞的百分数差异显著。中、重度异型增生以非整倍体为主,其细胞核DNA含量组方图相似于浸润癌。从细胞核DNA含量角度来看,中、重度异型增生是重要的癌前病变。     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Retinal projections to the lateral posterior-pulvinar complex in intact and early visual cortex lesioned cats

In intact cats, it is generally considered that the lateral posterior-pulvinar complex (LP-pulvinar) does not receive direct retinal terminals, with the exception of the retino-recipient zone known as the geniculate wing. There is, however, some evidence that early lesions of the visual cortex can occasionally induce the formation of novel retinal projections to the LP nucleus. Given the importance of knowing the connectivity pattern of the LP-pulvinar complex in intact and lesioned animals, we used the B fragment of cholera toxin, a sensitive anterograde tracer, to reinvestigate the retinal projections to the LP-pulvinar in normal cats and in cats with early unilateral lesions of the visual cortex (areas 17 and 18). Immunohistochemical localization of the toxin was performed to show the distribution and morphology of retinofugal terminals. A direct bilateral but predominantly contralateral retinal projection reached the caudal portion of LPl and LPm in the form of patches located mainly along its dorsomedial surface and many scattered terminals. The distribution of retinal projections to LP-pulvinar in intact and operated cats did not differ. Contrary to what had been previously reported, we found no evidence for lesion-induced sprouting of retinal axons in these higher-order thalamic nuclei. Retinal input to the LP-pulvinar might modulate visual responses driven by primary visual cortex or superior colliculus.     

Subchondroplasty in the treatment of bone Marrow lesion in early Knee Osteoarthritis: A systematic review of clinical and radiological outcomes

BackgroundKnee osteoarthritis (KOA) is increasingly prevalent in North American society. The significant societal burden it represents makes it essential to promote and target new treatments in earlier phases of the disease. Among others, subchondroplasty is a newly documented technique using calcium phosphate injection targeting the osteochondral lesions preceding KOA, also known as Bone Marrow Lesions (BMLs). This article aimed to review the existing literature on clinical and radiological outcomes of subchondroplasty in the treatment of BMLs in KOA.MethodA systematic review was performed using PubMed, Embase, Medline and Cochrane Database of Systematic Reviews. Studies on calcium phosphate injections into BMLs for KOA and its clinical and radiological outcomes were screened and reviewed by independent evaluators.ResultsAfter screening, ten articles were included, totaling 540 patients. Follow-up ranged from 6 months to 7 years. Overall, the procedure showed significant functional and quality of life improvement, as well as pain relief, as shown by Patients-Reported Outcomes Measures (PROMs). There were very few complications reported, the most important being leakage of calcium phosphate outside the targeted site. Conversion rate to total knee arthroplasty (TKA) ranged from 14 % to 30 % at 2 years post-procedure. Long term radiological outcomes have been poorly documented.ConclusionsSubchondroplasty is a promising avenue for the treatment of KOA. However, quality evidence is still required before any real conclusions and practical management guidelines can be drawn. Prospective, randomized studies with a control group and a rigorous assessment of long-term clinical and radiological outcomes are recommended.     

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.     

PIGQ glycosylphosphatidylinositol‐anchored protein deficiency: Characterizing the phenotype

PIGQ (OMIM *605754) encodes phosphatidylinositol glycan biosynthesis class Q (PIGQ) and is required for proper functioning of an N‐acetylglucosamine transferase complex in a similar manner to the more established PIGA, PIGC, and PIGH. There are two previous patients reported with homozygous and apparently deleterious PIGQ mutations. Here, we provide the first detailed clinical report of a patient with heterozygous deleterious mutations associated with glycosylphosphatidylinositol‐anchored protein (GPI‐AP) biosynthesis deficiency. Our patient died at 10 months of age. The rare skeletal findings in this disorder expand the differential diagnosis of long bone radiolucent lesions and sphenoid wing dysplasia. This clinical report describes a new and rare disorder—PIGQ GPI‐AP biosynthesis deficiency syndrome.     

Initiation of mouse-killing behavior following amygdaloid lesions in the rat(author's transl)]

Long-Evans hooded rats were tested for emotionality and observed by pairs in an open field for 6 consecutive days. Postoperative observations indicated that both emotionality and social cohesiveness were dramatically altered by ventromedial and anterolateral hypothalamic lesions. Tegmental, interpeduncular and habenular lesions were shown to have no effect on these behaviors. Alterations in behavior observed following hypothalamic ablations were related to septal and amygdaloid effects, and the possibility of separate projection systems for emotionality and social cohesiveness was discussed.