St Thomas' Hospital

About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.

Melanoma in congenital melanocytic naevi

Abstract: Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence, and therefore over clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that risk in childhood is related to the severity of the congenital phenotype, not only cutaneous but neuroradiological. New understanding of the genetics of CMN offers the possibility of improvement in diagnosis of melanoma, identification of those at highest risk, and new treatment options. We review the world literature and our centre's experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from our prospective cohort. Management strategies are proposed for presentation of suspected melanoma of the skin and the CNS in patients with CMN, including use of oral MEK inhibitors in NRAS-mutated tumours. This article is protected by copyright. All rights reserved.

Anticardiolipin antibodies--clinical associations.

Abstract: Attention was first drawn to the presence of an anticoagulant in patients with systemic lupus erythematosus (SLE) by Conley & Hartmann (1952) who described two patients with haemorrhagic disorders and prolonged prothrombin and whole blood clotting times. This anticoagulant appeared to act at the level of the prothrombin converter complex of the clotting cascade and prolonged all phospholipid dependent coagulation tests activated partial thromboplastin time (APTT), the Russell viper venom test (RVVT) and, less often, the prothrombin time. The thrombin time is usually normal. It became evident over the years that this 'lupus anticoagulant' was not particularly associated with bleeding but, paradoxically, with thrombosis (Mueh et al., 1982). A more sensitive and reliable technique of solid phase radioimmunoassay for the detection of antibodies to cardiolipin (a-CL) was devised by Harris et al. (1983a). Subsequent studies have shown a close relationship between these antibodies and the 'lupus anticoagulant', both members of a 'family' of antibodies to phospholipid, an integral part of the clotting cascade. However, phospholipids are also present in cell walls of endothelial cells, platelets and even neuronal cells and the actions of the antibodies against these phospholipids have been thought to be important in the pathogenesis of some of their clinical effects. Approximately 30% of patients with the 'lupus anticoagulant' or antibodies to cardiolipin will have a false positive test for syphilis. The VDRL test is usually of low titre (1:4-1:8) in these patients (Harris et al., 1985a). The mechanism of action of these antibodies remains obscure. Carreras et al. (1982) postulated that they may facilitate coagulation by preventing the release of arachidonic acid from blood vessel endothelium. Prostacyclin production is thereby reduced and platelet aggregation may occur. Inhibition of prekallikrein (Fletcher Factor) and the resulting impairment of fibrin clearance as a mechanism was suggested by Angles-Cano et al. (1979) and this mechanism has been demonstrated in several patients by Sanfellipo & Drayna (1983) and Elias & Eldor (1984). Comp et al. (1983) have described IgG from two patients with tht lupus anticoagulant that inhibited the function of human thrombomodulin, the endothelial co-factor in the activation of protein C by thrombin. Thus the feedback inhibition of coagulation by activated protein C is prevented. This has recently been verified by other workers (Cario et al., 1986). There is also a clear association with thrombocytopenia and Harris et al. (1985a) suggest that anticardiolipin antibodies may play a direct role in mediating platelet destruction. It has been postulated that lupus anticoagulants damage platelets and increase their adhesiveness initiating thrombosis (Editorial, 1984). It has been shown that a-CL antibodies may be of the IgG, IgM or IgA subclass. Harris et al. (1986) have recently demonstrated the importance of the actual levels of a-CL antibodies in predicting thrombosis, recurrent fetal loss or thrombocytopenia and this seems to hold true particularly for the IgG subclass, while a group of patients with drug-induced 'lupus anticoagulant' activity recently analysed were found to have predominantly IgM elevations which appeared to be unassociated with any of the thrombotic clinical complications (Gharavi et al., 1986). Investigations by Dr G.R.V. Hughes and his associates from 1983 onwards at the Hammersmith Hospital and the Rayne Institute of St. Thomas' Hospital, have led the way to further detecting and delineating the character of the antiphospholipid antibodies, their clinical associations and the efficacy ofvarious therapies in the prevention ofthe associated clinical complications. Since then, two International Conferences have been held in London with investigators from many countries participating and it has become clear that not only has the original finding of an association with thrombosis been confirmed but that the clinical associations of antiphospholipid antibodies now extend far beyond the original concept and that there is significant 'spill-over' to non-lupus patients and indeed to the general population.

Comparison of immunohistochemical labelling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB 45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma.

Abstract: A panel of three melanocyte differentiation antibodies has been compared with anti-S100 protein and NKIC3 in an assessment of benign and malignant melanocytic lesions. Anti-polyclonal S100 protein labelled all cases of primary cutaneous malignant melanoma, metastatic melanoma, desmoplastic melanoma and myxoid melanomas. In addition all benign and dysplastic naevi were positive. Conversely, HMB 45 was the least sensitive marker, labelling 24/31 primary cutaneous melanomas, 14/24 metastatic melanomas and only 1/6 desmoplastic melanomas. In the case of naevi, only junctional forms labelled consistently. Results for anti-melan-A and anti-tyrosinase were similar, although anti-tyrosinase proved slightly more sensitive in cases of malignant melanoma. NKIC3 revealed similar results to anti-tyrosinase, but had the disadvantage of reduced selectivity. It is concluded that anti-tyrosinase and anti-melan-A are useful additions to the panel of melanocytic monoclonal antibodies. In addition, both antibodies appear to have greater sensitivity for malignant melanoma than the conventionally used HMB 45 and could be considered as supportive markers to polyclonal anti-S100 protein in the diagnosis of malignant melanoma.

Specialization and integration of functional thalamocortical connectivity in the human infant

Abstract: Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue

Abstract: Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation.