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Biomedical subjects

S Lightman

Publications and source records attributed to S Lightman.

At least 19 recordsLinked to original sources

Comparison of the effects of frontal and temporal lobe partial seizures on prolactin levels.

The acute effects of partial (focal) epileptic seizures on serum prolactin levels were studied in two groups of patients: (1) 10 with temporal lobe seizures and (2) 11 with seizures that arose from the frontal lobes, recorded on cable video-electroencephalographic telemetry. Six of the eight complex partial seizures of temporal lobe origin were associated with a marked rise in prolactin levels at 10 minutes after onset (rise in levels, from a mean of 279 to 534 mU/L), compared with a rise in only one of the eight frontal lobe complex partial seizures. None of the five simple partial seizures (two of temporal and three of frontal lobe origin) was associated with a marked rise in prolactin levels. This difference in prolactin response following complex partial seizures of frontal and temporal lobe origin may help in the clinical differentiation of these seizures. A failure of prolactin levels to rise does not, however, exclude a diagnosis of complex partial seizures; thus, this measurement will not help in the clinical differentiation of frontal lobe complex partial seizures from psychogenic attacks.

Adolescent

Neuropeptide Y immunoreactivity in the spleen and thymus of normal rats and following adjuvant-induced arthritis.

Immunoreactive neuropeptide Y (irNPY) was detected by radioimmunoassay within the rat thymus and spleen. Total spleen and thymus irNPY contents in control animals were 77 +/- 3 ng and 23 +/- 1 ng respectively (means +/- S.E.M., n = 10). Total tissue contents of irNPY 14 days following bilateral adrenalectomy or induction of inflammatory arthritis were not significantly altered compared to controls. Most spleen irNPY coeluted with synthetic NPY after reversed-phase high-performance liquid chromatography, but two peaks of irNPY were detected in thymic extracts. This suggests that NPY may be differentially expressed in tissues of the immune system.

Animals

Increased expression and mutation of p53 in choroidal melanoma.

Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC-->AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma.

Animals

Transient vessel wall sheathing in acute retinal vein occlusions.

Three cases are reported which had features similar to, and evolved in a pattern consistent with central retinal vein occlusions and a fourth case is reported which behaved as a hemispheric vein occlusion. However, they differed from classic retinal vein occlusions by having prominent sheathing of the retinal venous vasculature at presentation, which in all four cases resolved within three weeks. There was no evidence for any of these cases having an inflammatory vasculitis. The significance of this transient sheathing is uncertain.

Acute Disease

Effect of lymphocytic infiltration on the blood-retinal barrier in experimental autoimmune uveoretinitis.

Using an experimental model of autoimmune uveoretinitis, we have examined the relationship of T cell infiltration in the retina to blood-retinal barrier (BRB) breakdown. Sensitive quantitative in vivo techniques were used to examine BRB permeability to sucrose, a low mol. wt non-transported solute. Electron microscopy was also used to localize extravasated horseradish peroxidase, a macromolecular visual tracer, from the retinal vasculature and to identify the route by which any leakage was occurring. No increase in BRB permeability was found prior to lymphocytic infiltration. By day 10 of the disease inflammatory cells could be seen within the structurally intact retina, which was shortly followed by an increase in the permeability of the BRB to sucrose. Only later in the disease process, when damage to the photoreceptor layer became apparent, did extravasation of the macromolecule HRP occur. At no stage of the disease process was there any detectable damage to inter-endothelial tight junctions. The size-dependancy of tracer extravasation in the initial stages of the disease is indicative of a paracellular route being responsible for the increase in BRB permeability. In later stages of the disease some evidence of horseradish peroxidase filled 'vesicle-like' profiles was observed. We suggest that the devastating complication of BRB breakdown in ocular inflammation is a direct consequence of lymphocytic infiltration.

Animals

Surgically induced necrotising sclerokeratitis (SINS)--precipitating factors and response to treatment.

The clinical features, treatment, and visual outcome of 52 eyes from 43 patients who developed scleritis following surgery were reviewed. In all patients the scleral inflammation developed adjacent to a surgical wound. Ninety six per cent had necrotising disease and 23% also had evidence of secondary posterior scleritis. Many different types of ocular surgery were implicated and the majority (75%) of the patients had two or more surgical procedures before the onset of the scleritis. Although cataract extraction through a limbal incision resulted in the largest subgroup, scleritis also followed glaucoma, strabismus, and retinal detachment surgery. The latent period between surgery and the appearance of inflammation was short (mean 9 months) except for a small group in whom scleritis occurred many years after squint surgery. Sixty three per cent of patients had evidence of a systemic disease. Early diagnosis and aggressive medical treatment significantly improved the visual outcome. The precipitating factors, pathogenesis, and course of this condition are discussed.

Adult

Immunopathology and altered immunity in posterior uveitis in man: a review.

Posterior uveitis is thought to be a T-cell mediated disease since active foci of inflammation, identified in eyes enucleated for the complications of intraocular inflammation, are found to be predominantly composed of CD4+ T-cells. Few B-cells and little immunoglobulin are found suggesting that antibody and immune complex deposition do not play a major role in perpetuating the inflammatory process. As ocular biopsy is not a feasible method for monitoring disease activity and response to treatment, parameters of T-cell activation and retinal damage have been studied in the peripheral blood. These have included antibody and T-cell sensitisation to retinal S-antigen, serum soluble IL-2 receptors and IL-2 receptors on activated T-cells. none of these parameters, however, have been found to be useful in the monitoring of ocular disease activity alone or in the prediction of disease relapse.

Antigen-Antibody Complex

Uveitis: management.

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Administration, Topical

Use of steroids and immunosuppressive drugs in the management of posterior uveitis.

Posterior uveitis can occur in all age-groups and often has devastating effects on vision. The visual loss can have a variety of causes including cataract formation, vitritis, optic nerve damage and macular oedema. In patients with active inflammatory disease resulting in reduced vision, steroids are still the best drug but cyclosporin is becoming widely used in combination with steroid therapy, in patients who do not respond to steroids alone or in whom the dose of steroids required to control the disease process is unacceptably high. Cyclosporin works specifically on activated T-lymphocytes and does not therefore result in bone marrow suppression like the more conventional immunosuppressive drugs. This paper discusses the indications for treatment in patients with posterior uveitis and how to use steroids, cyclosporin and other immunosuppressive drugs in the management of this condition.

Administration, Oral

Vascular changes in the posterior segment in clinical and experimental ocular inflammatory disease.

Posterior segment inflammatory disease can have several different effects on the retinal vasculature, all of which have potentially sight threatening consequences. Blood-retinal barrier breakdown is a common feature of the disease process with resulting retinal and macula oedema. Very little is known about the mechanism of this breakdown and in particular whether it is at the endothelial cell membrane or at the tight junctions between the endothelial cells--a matter of importance if better therapeutic regimes are to be devised in the future. This paper looks at this question in two animal models of posterior uveitis using different techniques.

Animals

Effect of a long-acting somatostatin analogue (BIM23014) on proliferative diabetic retinopathy: a pilot study.

A pilot study on the use of a continuous infusion of somatostatin, by subcutaneous pumps in the management of proliferative diabetic retinopathy is reported. Two patients out of eight with proliferative retinopathy demonstrated improvement. One patient demonstrated regression of disc new vessels and the other a reduced area of retinal capillary non-perfusion, both demonstrated by fluorescein angiography. Control patients showed worsening of fluorescein leakage over the observation period of four to six weeks whereas the other six patients given the somatostatin infusion did not demonstrate any deterioration. The mechanism of action of somatostatin in this study is unknown but it is thought to have direct anti-angiogenic properties as well as inhibiting growth hormone secretion.

Adult

Cavernous sinus involvement in recurrent Nelson's syndrome.

Nelson's syndrome is rare and difficult to cure. The tumours in this condition may behave invasively and require multiple interventions. Two patients who had been followed up for nearly 20 years developed signs of cavernous sinus involvement, one with an empty sella. Long term follow-up for such patients is emphasized.

Adult

Sclerokeratitis after keratoplasty in atopy.

The authors report a series of five markedly atopic patients in whom a severe sclerokeratitis developed within 1 to 4 weeks of keratoplasty. The onset was acute with discomfort, photophobia, hyperemia, and mucus production. This resulted in early loosening of sutures and was associated with microbial keratitis in two cases and graft rejection in one. The inflammatory reaction was controlled with high-dose oral steroids and did not recur when the treatment was terminated. Serum IgE levels were elevated in all these patients (range, 421-8434 kU/l). Binding of this IgE onto the surface of mast cells in the conjunctiva with subsequent degranulation may be involved in the pathogenesis of the induced inflammation. Principal recommendations include the use of interrupted sutures and early immunosuppression with high-dose oral steroids at the onset of this condition together with the control of risk factors for microbial keratitis.

Adolescent