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Biomedical subjects

L Cassidy

Publications and source records attributed to L Cassidy.

At least 19 recordsLinked to original sources
PubMed2003

Vestibular perception in patients with acquired ophthalmoplegia.

Using a perceptual technique it is shown that patients with chronic external ophthalmoplegia have shortened vestibular responses. It is postulated that this is secondary to the retinal image slip experienced by these patients during head movements and a useful compensatory mechanism to suppress motion-induced sickness and spatial disorientation.

Adult↗
PubMed2001

Elevated visual motion detection thresholds in adults with acquired ophthalmoplegia.

AIMS: To test the hypothesis that in patients with acquired chronic bilateral ophthalmoplegia, abnormal retinal image slippage during head movements would result in abnormal thresholds for visual perception of motion. METHODS: Five patients (two males and three females) with ophthalmoplegia were included in the study. The average age was 44 years (range 30-69 years). The aetiology of ophthalmoplegia was myasthenia gravis (MG; n=2), chronic progressive external ophthalmoplegia (CPEO; n=2), and chronic idiopathic orbital inflammation. Visual motion detection thresholds were assessed using horizontal and vertical gratings (spatial frequency) set at thresholds for visibility. The grating was then accelerated at 0.09 deg/s(2). The subject's task was to detect the drift direction of the stimulus. RESULTS: Visual motion detection thresholds were raised to a mean of 0.434 deg/s (SD 0.09) (mean normal value 0.287 deg/s (SD 0.08)) for horizontal motion; and to a mean of 0.425 deg/s (SD 0.1) (mean normal value 0.252 deg/s (SD 0.08)) for vertical motion. The difference in values for both horizontal and vertical motion detection were statistically significant when compared with age matched controls; p <0.023 for horizontal motion and p<0.07 for vertical motion (two tailed t test). CONCLUSION: Abnormally raised visual motion thresholds were found in patients with ophthalmoplegia. This may represent a centrally mediated adaptive mechanism to ignore excessive retinal slip and thus avoid oscillopsia during head movements.

Adult↗
PubMed2001

Outcome of lens aspiration and intraocular lens implantation in children aged 5 years and under.

AIMS: To determine the visual outcome and complications of lens aspiration with intraocular lens implantation in children aged 5 years and under. METHODS: The hospital notes of all children aged 5 years and under, who had undergone lens aspiration with intraocular lens implantation between January 1994 and September 1998, and for whom follow up data of at least 1 year were available, were reviewed. RESULTS: Of 50 children who underwent surgery, 45 were eligible based on the follow up criteria. 34 children had bilateral cataracts and, of these, 30 had surgery on both eyes. Cataract was unilateral in 11 cases; thus, 75 eyes of 45 children had surgery. Cataracts were congenital in 28 cases, juvenile in 16, and traumatic in one case. The median age at surgery was 39 months (range 11-70 months). Follow up ranged from 12-64 months (median 36 months). Of 34 children with bilateral disease, 25 (73.5%) had a final best corrected visual acuity of 6/12 or better, while seven (20.5%) achieved 6/18 or less; in one child the vision improved from UCUSUM to CSM but another, who had only one eye operated on, was unable to fix or follow with this eye preoperatively or 2 years postoperatively. Of 11 children with unilateral cataract, five (45.5%) had a final best corrected visual of 6/12 or better, and six (54.5%) 6/18 or less. A mild fibrinous uveitis occurred in 20 (28.2%) eyes in the immediate postoperative period, but resolved with topical steroids. One child had a vitreous wick postoperatively requiring surgical division. Glaucoma, endophthalmitis, or retinal detachment have not been observed so far in any patient postoperatively. CONCLUSION: From this series the authors suggest that, in children aged 5 years and under, lens aspiration with intraocular lens implantation is a safe procedure, with a good visual outcome in the short term. Further studies are needed to investigate these outcomes in the long term.

Anti-Inflammatory Agents↗
PubMed2000

Ophthalmic complications of childhood medulloblastoma.

BACKGROUND: To study the ophthalmic complications and sequelae in children surviving medulloblastoma in order to assess the need for therapeutic intervention by the ophthalmologist. PROCEDURE: We identified all children attending the Leeds General Infirmary and St. James' University Hospital for treatment of medulloblastoma in the period January 1990 to March 1997, and the notes of all surviving patients were reviewed. Those patients who had not had an ophthalmic assessment within the last 6 months were recalled for examination. RESULTS: Twenty-four surviving patients underwent full ophthalmic assessment. The follow-up period ranged between 6 months and 7 years (range 3.6 yr): 66% had ocular symptoms at presentation; 25% developed ocular complications following treatment; 50% were left with ocular sequelae; 41% percent required ophthalmic intervention (25% medical/orthoptic intervention; 16% surgical intervention). CONCLUSIONS: Early (preferably preoperative) referral to the ophthalmology department is important in order to ensure appropriate management of diplopia, preservation of binocular single vision, and prevention of amblyopia in younger children.

Abducens Nerve Diseases↗
PubMed1999

Congenital cataract and multisystem disorders.

A knowledge of those syndromes associated with congenital cataract is essential for the paediatric ophthalmologist, as congenital cataracts are manifest in a large number of syndromes. It is important to have the correct diagnosis in such cases, not only for genetic and prognostic information, but also in order to help the parents to understand their child's condition. This paper describes the more common syndromes seen in association with congenital cataract, and emphasises the importance of looking at the whole child and family. We aim to provide a practical clinical guide to the diagnosis of hereditary and non-hereditary syndromes associated with congenital cataract.

Abnormalities, Multiple↗
PubMed1999

Melanocytes adhere to and synthesize laminin-5 in vitro.

Melanocytes arise from the neural crest, migrate to the skin, and can be detected in the basal layer of the epidermis in skin biopsies of human fetuses as early as 11 weeks gestational age. During post-natal life, melanocytes reside at the basal layer of the epidermis, but the ligands to which they attach are unknown. Laminin-5 is a component of anchoring filaments of the lamina lucida of the epidermal basement membrane. In this report we show that human melanocytes adhere to purified laminin-5 to a level comparable with normal human keratinocytes. Blocking antibodies to the 165 kDa subunit of laminin-5 significantly inhibited fetal and neonatal melanocyte attachment to the surface of salt-split skin, which exposes laminin-5 on its surface, suggesting that laminin-5 is a ligand for melanocyte attachment to the basement membrane in vivo. Western blotting of concentrated culture supernatant of fetal and neonatal melanocytes with anti-laminin-5 antibodies demonstrated a single immunoreactive band of the expected size of laminin-5. In contrast, 3 human metastatic melanoma cell lines did not produce laminin-5. Immunofluorescence microscopy with antibodies to each of the three chains of laminin-5 confirmed the presence of laminin-5 in a peri-cellular distribution around melanocytes, but not melanoma cells. Our results suggest that laminin-5 may be a ligand for normal human melanocytes in the basement membrane, and that loss of laminin-5 production by melanoma cells may be a marker for malignant transformation.

Cell Adhesion↗
PubMed1998

Rac1 mediates dendrite formation in response to melanocyte stimulating hormone and ultraviolet light in a murine melanoma model.

Melanocytes are pigment producing cells that reside in the basal layer of the epidermis, and form multiple long dendritic processes that transport melanosomes from the melanocyte cell body to the dendritic tips, and then to keratinocytes. Dendrite formation requires actin polymerization in the newly forming dendrite, and dendrite formation in melanocytes is stimulated by hormones and ultraviolet light. The rho-subfamily of monomeric guanosine triphosphate-binding proteins is implicated in remodeling the cellular actin cytoskeleton, resulting in the formation of filopodia, lamellipodia, and stress fibers, as well as in oncogenesis and activation of the Jun/p38 mitogen activated kinase cascade. In this paper we show that rac1 induces the formation of dendrite-like structures when activated mutants are transiently expressed in B16F1 murine melanoma cells and in four human melanoma cell lines. Activated mutants of cdc42 and rhoA induced the formation of filopodia and stress fibers, respectively, in B16F1 cells, but not dendrites. A dominant negative inhibitor of rac1 abrogated the ability of alpha-melanocyte stimulating hormone, a peptide hormone known to stimulate melanocyte dendrite formation, and ultraviolet light, to induce dendrite formation in B16F1 cells, and alpha-melanocyte stimulating hormone and ultraviolet light stimulated the localization of rac1 to dendrite cell membranes. These results suggest that rac1 is an important signaling intermediate in dendrite formation in B16F1 cells, and that rac1 mediates the well-known ability of alpha-melanocyte stimulating hormone and ultraviolet light to induce dendrite formation.

Actins↗
PubMed1998

Platelet derived growth factor and fibroblast growth factor basic levels in the vitreous of patients with vitreoretinal disorders.

AIM: To determine the potential role of basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) in the pathogenesis of proliferative vitreoretinopathy (PVR). METHODS: An enzyme linked immunosorbent assay technique was used to determine the quantities of bFGF and PDGF in 38 vitreous samples taken from patients undergoing trans pars plana vitrectomy (PPV) for a variety of vitreoretinal disorders. RESULTS: bFGF levels ranged from undetectable to 318.7 pg/ml. The mean concentration was 27.57 pg/ml. PDGF levels ranged from undetectable to 160 pg/ml, the mean concentration being 40.06 pg/ml. Eight of 13 patients with clinical evidence of retinal detachment (RD) and PVR had significantly elevated bFGF concentrations, whereas only one of 11 patients with RD and no PVR had detectable bFGF; seven of eight patients with RD and PVR had elevated PDGF concentrations in the vitreous, whereas all 10 patients with RD and no PVR had no detectable vitreous PDGF. Eight patients with vitreous haemorrhage had raised PDGF concentrations, and the levels were particularly high (> 120 pg/ml) in those two patients with active neovascularisation. Two out of nine patients with vitreous haemorrhage had raised bFGF levels. CONCLUSIONS: bFGF and PDGF concentrations are elevated in PVR even in the absence of vitreous haemorrhage, and not in patients with RD uncomplicated by PVR. This observation suggests that both cytokines may be involved in the pathogenesis of PVR.

Adolescent↗
PubMed1997

Alpha-melanocyte-stimulating hormone and endothelin-1 have opposing effects on melanocyte adhesion, migration, and pp125FAK phosphorylation.

Recent reports show that alpha-MSH (melanocyte-stimulating hormone) is mitogenic and melanogenic for normal human melanocytes, and that this effect is mediated through binding to the melanocortin receptor (MC1R) and activation of cAMP formation. alpha-MSH has also been shown to induce changes in cell shape in melanocytes and melanoma cells, particularly increased dendricity, suggesting a potential role for alpha-MSH in melanocyte-matrix interactions and pigment transfer through reorganization of the melanocyte actin filament cytoskeleton. In this report we show that the potent alpha-MSH analog (Nle4, D-Phe7)-alpha-MSH (NDP-MSH) induces reorganization of the actin stress fiber cytoskeleton in treated human melanocytes and that this reorganization is associated with increased adhesion to fibronectin (FN). Because most melanocyte growth factors act synergistically on melanocyte mitogenesis, we also sought to determine the effect of the melanocyte mitogen endothelin-1 (ET-1) on the melanocyte actin cytoskeleton, melanocyte adhesion, and melanocyte migration. We show that ET-1, which increases melanocyte migration on FN, has opposite effects on melanocyte adhesion to FN compared with NDP-MSH and that endothelin-1-induced actin reorganization is distinct from that observed following NDP-MSH treatment. Finally, we show that focal adhesion kinase (pp125FAK), a nonreceptor tyrosine kinase associated with focal contact formation and cell migration, is phosphorylated on tyrosine residues after treatment of melanocytes with ET-1, but not NDP-MSH. These data indicate that while alpha-MSH and ET-1 act synergistically to modulate melanocyte proliferation, they have opposite effects on melanocyte-matrix interactions.

Actins↗
PubMed1997

Fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent mechanism.

Recent reports show that components of the extracellular matrix function as cell survival factors through the suppression of apoptosis (programmed cell death). In this report we show that attachment to fibronectin suppresses apoptosis of normal human fetal and neonatal melanocytes in vitro and that prevention of attachment to underlying matrix or attachment to poly-L-lysine is a potent inducer of apoptosis in melanocytes. A role for the beta1-integrin family in mediating cell survival signals was shown by the ability of beta1-blocking antibodies to enhance apoptosis in melanocytes attached to fibronectin, and by the ability of anti-beta1 antibodies immobilized on solid supports to suppress apoptosis in melanocytes. Cytochalasin D reversed the effect of fibronectin on the suppression of apoptosis in melanocytes, suggesting that an intact cytoskeleton is required for transduction of survival signals. A human metastatic melanoma cell line, SKMEL28, was resistant to apoptosis when grown in suspension or on poly-L-lysine, even after 4 d in culture in the absence of exogenous growth factors. These results suggest that fibronectin suppresses apoptosis in normal human melanocytes through an integrin-dependent pathway and that significant differences in the control of anchorage-dependent regulation of apoptosis exist in melanocytes and melanoma cells.

Antibodies↗
PubMed1997

Are reported stress and coping style associated with frequent recurrence of genital herpes?

OBJECTIVES: This paper reports on the cross sectional data from the longitudinal study examining the impact of genital herpes simplex virus (HSV) infection on quality of life. In particular the report sought to study the relation between recurrence of genital HSV and coping style, mood, personality, and quality of life, among other factors. SETTING AND SUBJECTS: 116 patients with a known history of genital herpes simplex infection attending the Department of Genitourinary Medicine at Chelsea and Westminster Hospital. METHODS: Psychosocial factors (stress, anxiety, depression, health locus of control, personality, social support, coping skills, and quality of life) and the reported frequency of genital herpes episodes were measured using self administered questionnaires designed to examine the relation between psychosocial status and the frequency of genital HSV episodes. RESULTS: The number of recurrences reported by patients was significantly related to the style of coping skills used. Higher recurrences were less likely to use problem focused coping skills of planning and active coping, and the emotion focused coping skills of positive reinterpretation and growth. There was a significant difference in the number of patients who believed that psychological stress was related to the number of recurrences they experienced. This belief was related to neuroticism on the Eysenck Personality Questionnaire scale, and not to any of the other measures investigated. CONCLUSION: The findings suggest that it is the way individuals cope, and their personality characteristics rather than actual levels of psychological stress, that influence their belief in a link between recurrent genital HSV and stress. HSV may become the focus of existing concerns and be viewed as the physical manifestation of stress.

Adaptation, Psychological↗