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Biomedical subjects

S Lightman

Publications and source records attributed to S Lightman.

At least 91 records · Page 5Linked to original sources
PubMed1996

Microvessel count predicts survival in uveal melanoma.

Microvessel density has become established as an important prognostic indicator for many tumor types. This study investigates the microvessel density as a prognostic factor for survival in patients with uveal melanoma, which is the commonest intraocular tumor and has a clear tendency for metastatic spread to the liver. Factor VIII-related antigen was identified immunohistochemically in bleached sections from 123 tumors. Maximum blood vessel density in an area of 0.25 mm2 was recorded, along with other accepted prognostic information. Microvessel density was the single most important prognostic factor on univariate testing, and in a Cox proportional hazard model, tumor size was the only other variable to be entered. No other accepted prognostic factor entered the model. We conclude that microvessel density is an important prognostic factor for survival in patients with uveal melanoma and allows the identification of high-risk patients for whom adjuvant therapy should be considered.

Biomarkers, Tumor↗
PubMed1996

Managing HIV. Part 5: Treating secondary outcomes. 5.11 HIV and eye disease.

Blindness is a threatening complication of HIV infection, but one that can be prevented by correct diagnosis and management of ocular disease. The general practitioner can play a vital role in diagnosis by being familiar with the types of ocular disease seen at different stages of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Ophthalmology.

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Ambulatory Surgical Procedures↗
PubMed1996

Lymphocyte migration across the anterior and posterior blood-retinal barrier in vitro.

The migration of lymphocytes through monolayers of rat retinal pigment epithelium (RPE) and retinal vascular endothelium, which form the posterior and anterior blood-retinal barrier (BRB) respectively, was investigated in vitro. After a 4-hr assay the migration of untreated peripheral lymph node (PLN) cells through RPE monolayers was negligible (<1%) with only a small increase found after activation of the PLN cells with concanavalin A or by cross-linking CD3. Activation of the RPE with IFN-gamma augmented migration with maximal PLN cell migration being achieved with a combination of CD3 cross-linking and IFN-gamma activation (17% migration). The highest level of lymphocyte migration was observed with three CD4+ antigen-specific T cell lines specific for purified protein derivative (PPD; 33% migration), ovalbumin (OA; 31%), and S-antigen (S-Ag; 57%). Migration of both untreated and Con A-activated PLN cells through retinal endothelial cells (EC) from PVG rats was negligible, whereas the migration of the antigen-specific T cell lines was 23, 29 and 23% for PPD, OA, and S-Ag lines, respectively. Migration of these cell lines through retinal endothelium derived from Lewis rats was significantly greater (44% for PPD, 39% for OA, and 39% for S-Ag) which corresponded with a greater expression of ICAM-1 on the EC.

Animals↗
PubMed1996

The painful eye.

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Anti-Bacterial Agents↗
PubMed1996

The effect of TNF-alpha and IL-6 on the permeability of the rat blood-retinal barrier in vivo.

The blood-retinal barrier (BRB), which is formed by the retinal vascular endothelium and the retinal pigment epithelium, is responsible for controlling the passage of cells and molecules into the neuroretina. During ocular inflammatory diseases, however, this selective control is altered due to changes in BRB function such as increased permeability and leucocyte recruitment. The causative factors leading to barrier breakdown are not entirely understood although cytokines have recently been implicated. We have investigated the effect of the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) upon the integrity of the rat BRB. Lewis rats received a dose of each cytokine by intravitreal injection and the permeability of the BRB was assessed using the smaller molecular weight vascular tracer 14C mannitol. A significant opening of the barrier to mannitol was detected following an intravitreal injection of 2 x 10(4) U of TNF-alpha which persisted from day 1 to day 5 post-injection (PI). The permeability of the BRB returned to normal values by day 7 PI. Only occasional mononuclear inflammatory cells were seen in the retina and vitreous of the TNF-alpha-treated eyes although they remained in evidence up to day 5 PI. In the TNF-alpha-infected eye there was immunohistological evidence of activation of tissue-resident cells, particularly in the inner plexiform layer. Of particular interest was the observation that the BRB of the non-injected contralateral eye also exhibited increased permeability over a similar time-course but without any evidence of cellular infiltration or activation of tissue-resident cells. Unlike TNF-alpha, the administration of 1 x 10(3) U of IL-6 into the vitreous caused no measurable increase in BRB permeability despite inducing a small infiltration of inflammatory cells.

Animals↗
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗
PubMed1995

The kinetics of cytokine mRNA expression in the retina during experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) was induced in Lewis rats and the inflamed retinas were examined for IFN-gamma, IL-2, IL-4, and IL-10 mRNA production at serial time points using the reverse transcriptase-polymerase chain reaction. IFN-gamma, IL-2, IL-4, and IL-10 mRNAs were all detected 24 hr before the earliest time point at which histological changes have previously been detected. IFN-gamma, IL-2, and IL-4 mRNA expression peaked during the active phase of the disease and declined in parallel with lymphocyte numbers as the inflammation resolved. IL-10 mRNA levels increased more slowly, reaching a maximum at later stages of disease. The observed pattern of cytokine mRNA expression in the retina in EAU is similar to that reported in experimental autoimmune encephalomyelitis (EAE). The increase in IL-10 mRNA expression in late disease may reflect a role in disease resolution as previously proposed in EAE.

Animals↗
PubMed1995

Estrogen and progesterone receptor analysis in ocular melanomas.

BACKGROUND: It has been suggested that pregnancy may promote metastases in melanoma and that the contraceptive pill may be an etiologic factor. The purpose of this study is to determine if uveal or conjunctival melanomas express estrogen or progesterone receptors. METHODS: Twenty-seven choroidal and five conjunctival melanomas were investigated. Immunohistochemistry was performed using the antibodies ER-D5, which recognizes heat-shock protein 27 (formerly called the estrogen receptor-associated cytoplasmic antigen); ER-1D5, which recognizes the estrogen receptor; and PgR, which recognizes the progesterone receptor. RESULTS: Most of the conjunctival and uveal melanomas stained strongly for heat-shock protein 27 but none of the tumors showed positive nuclear staining for either the estrogen or the progesterone receptor. CONCLUSIONS: No evidence was found for either estrogen receptor or progesterone receptor expression in choroidal or conjunctival melanomas. Based on the literature, there is little evidence for these hormones having a role in the development or progression of these tumors.

Adult↗
PubMed1995

The detection of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction.

Both cutaneous and uveal melanoma undergo haematogenous dissemination. Detection of tyrosinase mRNA by reverse transcription-polymerase chain reaction (RT-PCR) has been described as an extremely sensitive way of detecting circulating viable melanoma cells in the peripheral venous blood, and this technique may be of value in the early detection of dissemination. Also, it has been suggested that surgical manipulation of the eye, such as occurs during enucleation, can provoke uveal melanoma dissemination. The purpose of this study was to evaluate whether tyrosinase mRNA is detectable in the peripheral blood of patients with uveal and cutaneous melanoma and in patients with uveal melanoma undergoing surgical procedures on the eye harbouring the tumour. Venous blood samples from 36 patients diagnosed as having active uveal melanoma and from six patients with advanced metastatic cutaneous melanoma were analysed. In addition, blood samples were spiked with known numbers of cells from three cell lines and four primary uveal melanoma cultures. The reported sensitivity of the technique was confirmed, with an ability to detect down to one cell per ml of blood. All 51 blood samples from the 36 patients with uveal melanoma were negative, and this included 20 perioperative blood samples. The test was also negative for the six patients with advanced cutaneous melanoma. There were two positives among 31 control samples analysed. This study demonstrates that there are far fewer circulating viable melanocytes than has been previously supposed in patients with melanoma and that the RT-PCR is of no clinical value in detecting metastatic melanoma disease. There was no evidence for surgery causing a bolus of melanoma cells to enter the peripheral circulation.

Base Sequence↗
PubMed1995

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

AIDS-Related Opportunistic Infections↗
PubMed1995

Therapeutic considerations: symptoms, cells and mediators.

Immuno-histopathological studies of conjunctival tissue biopsied from patients with non-sight-threatening allergic conjunctivitis or with sight-threatening allergic keratoconjunctivitis should lead to more effective management of these eye conditions, based on the specific cellular involvement. The major difference between these two categories of eye disease was the occurrence of T-lymphocytes, which were absent in the former but prominent in the sight-threatening disorders. Seasonal and perennial allergic conjunctivitis both showed a heavy mast cell increase, due to infiltration of mucosal type mast cells, and allergen challenge studies linked mast cell histamine release to the early phase reaction occurring within 20 minutes. A second histamine peak at six hours after challenge might implicate basophils (or refractory mast cells) and was accompanied by a rise in eosinophil cationic protein. In sight-threatening, chronic allergic keratoconjunctivitis the responses were clearly directed by T-cells, themselves the primary effector cell in atopic keratoconjunctivitis, whereas vernal keratoconjunctivitis displayed a T-cell driven eosinophilia, with increased expression of the adhesion molecules involved in tissue invasion by these cells. Appropriate therapies for each different category of conjunctivitis should be based on the specific immunopathology, and directed at the activated cell types that are primarily responsible for the disease process.

Blindness↗
PubMed1995

Role of cyclophosphamide and high dose steroid in ocular cicatricial pemphigoid.

AIMS/BACKGROUND: Ocular cicatricial pemphigoid (OCP) can present with severe conjunctival inflammation that requires systemic immunosuppression to avoid serious ocular morbidity. This study aimed to assess the clinical response to cyclophosphamide and short term, high dose prednisolone in this group of patients. METHODS: A prospective, unmasked study assessed patients presenting with either 'severe' ocular inflammation (n = 4) or 'marked' or 'severe' ocular inflammation that had failed to respond to other systemic immunosuppression (n = 6). Nineteen inflamed eyes of 10 consecutive patients were enrolled. RESULTS: The ocular inflammation resolved in 15 eyes in a mean time of 2.4 months. Two eyes perforated despite treatment and one patient was unable to tolerate the medication. Progressive cicatrisation occurred in 21%. CONCLUSION: Cyclophosphamide and short term, high dose prednisolone are effective in severe inflammation caused by OCP but may not completely prevent cicatrisation.

Administration, Oral↗
PubMed1995

Cloning and expression of melanin-concentrating hormone genes in the rainbow trout brain.

Salmonids, a group of tetraploid fish including salmon and trout, produce the vertebrate neuropeptide melanin-concentrating hormone (MCH) in a group of hypothalamic magnocellular neurons in the nucleus lateralis tuberis (NLT). NLT neurons project both to the brain and to the neural lobe of the pituitary gland from where MCH is released into the circulation to play a central role in camouflage (+/- stress). We have cloned and sequenced the MCH1 and MCH2 genes from the rainbow trout, Oncorhynchus mykiss, and used the data firstly to examine the position of O. mykiss in salmonid phylogeny, and secondly to enable central nervous system MCH1 and MCH2 gene expression to be mapped. In the immature adult female trout brain, only MCH2 was detectable at the hybridization stringency used. In addition to the known location of MCH-positive neurons, immunocytochemistry and in situ hybridization histochemistry revealed a previously undescribed nucleus of MCH-positive neurons located more dorsal and posterior to those of the NLT, over the paraventricular organ of the lateral ventricular recess. Axons from this second group of MCH neurons project dorsally into the brain, while a few extend down toward the lateral ventricle near the paraventricular organ. They make little, if any, direct contact with the neurohypophysis, and thus may subserve a central function, unrelated to hormonal colour regulation.

Amino Acid Sequence↗
PubMed1995

Therapeutic options in ocular allergic disease.

The term ocular allergy encompasses a group of diseases in which there is a high frequency of atopy, ocular itching, stringy discharge and a papillary conjunctival reaction. Conditions confined to the lids and conjunctiva (e.g. seasonal allergic conjunctivitis) have a good prognosis but those involving the cornea may result in visual impairment (e.g. atopic keratoconjunctivitis). Mast cell and eosinophil mechanisms are important in al the ocular allergies, but T cell inflammation is prominent only in vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Therapy involves the use of antigen avoidance (where possible), nonspecific medical therapy (e.g. cold compresses, artificial tears), specific medical therapy and, in certain situations, immunotherapy and surgery. Topical antihistamines (often in combination with a vasoconstrictor) and oral antihistamines are widely used in perennial and seasonal conjunctivitis. Levocabastine is a new preparation which is more rapid and potent. Mast cell inhibitors [e.g. sodium cromoglycate (cromolyn sodium)] have a proven track record as safe and effective therapy for all ocular allergic diseases and the newer, more potent nedocromil and lodoxamide are now available. Topical steroids are only indicated in sight-threatening disease due to their serious adverse effects and other therapy should be continued to minimise the dose required. There is a lack of intermediate potency and high potency but safe topical preparations. A number of future possibilities exist, some of which have been partially explored. Cyclo-oxygenase inhibitors have proved of limited use, but inhibitors of lipoxygenase and kinin pathways are awaited. Although results with HEPP have been disappointing, other modulators of mast cell function (e.g. picumast, beta-agonists and phosphodiesterase inhibitors) may prove useful in the future. So far, results with topical cyclosporin in serious disease are very encouraging. Future developments in the manipulation of eosinophilic products, cytokines and adhesion molecules may also be relevant. However, the current situation for those with serious ocular allergy remains a disturbing dependence upon topical steroids, with all the attendant risks.

Anti-Allergic Agents↗