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Biomedical subjects

P McCluskey

Publications and source records attributed to P McCluskey.

At least 19 recordsLinked to original sources
PubMed2006

Idiopathic orbital inflammation with extraorbital extension: case series and review.

Idiopathic orbital inflammation (IOI) is a well-recognised pathological process usually confined to the orbit. It is an orbital mass lesion characterised by infiltration of soft tissues by inflammatory cells and fibrous tissue. It is essentially a diagnosis of exclusion. Extraorbital extension (EOE) is rare and, to the best of the authors' knowledge, inclusive of our series, there have been 22 cases of IOI with EOE reported in the literature. We describe four patients with IOI with EOE-their presentation, histopathological findings and management strategies. Histopathology of three patients revealed sclerosing and one had a nonspecific variant of IOI. In our series, all four patients required additional immunosuppression. Hence, corticosteroid therapy often needs to be supplemented by radiotherapy and/or immunosuppressive therapy.

Adult↗
PubMed2006

Outcome of graft free Molteno tube insertion.

AIMS: To determine the long term outcome of Molteno implants inserted using a modified surgical technique that eliminates the need for a donor scleral graft. METHODS: Retrospective case series involving a medical record analysis of 35 consecutive patients undergoing first Molteno implant surgery for refractory glaucoma. The main outcomes included life table analysis of intraocular pressure control following surgery and frequency of intraoperative and postoperative complications. RESULTS: There were no complications related specifically to the modified method of tube placement. Medium term intraocular pressure control was similar to other series. CONCLUSIONS: This simplified method for the insertion of Molteno implants eliminates the need for a donor scleral graft while maintaining the implant's ability to control intraocular pressure.

Adult↗
PubMed2005

Avoiding free nipple grafting with the inferior pedicle technique.

In cases of severe macromastia, the free nipple graft technique has been the traditional alternative to pedicle transposition. Distress over nipple survival in large reduction mammaplasty and long pedicle transposition is largely responsible for this.A retrospective investigation of the records of 142 reduction mammaplasty patients was carried out to determine whether nipple survival or overall complication rates were significantly different in patients undergoing larger (>1500 g per side) as compared with smaller reductions (< 1500 g per side). The 2 patient groups were compared with respect to mild or severe complications. Data were analyzed using Fisher exact test and 2-sample t tests. A P value of < 0.05 was considered statistically significant. No patient in either group had total nipple loss. There were no statistically significant differences in major or minor complications between the 2 groups. In our experience, the inferior pedicle, Wise pattern reduction is a reliable and predictable method of reduction, appropriate for all breast sizes and pedicle lengths.

Adult↗
PubMed2005

Human retinal microglia express candidate receptors for HIV-1 infection.

BACKGROUND/AIMS: Microglia are the primary antigen presenting cells in the central nervous system and the retina, and can harbour viral antigens that may damage neural tissue via the release of neurotoxins. All cells bearing CD4 molecules and co-receptors (members of the chemokine receptor and Fcgamma receptor families) are potential targets for the human immunodeficiency virus (HIV). In this study, retinal microglia (in vitro and in situ) were investigated for the expression of candidate HIV-1 binding receptors. METHODS: Cultured human retinal microglia and frozen sections of human retinas were used. Immunohistochemistry was used to investigate expression of cell surface receptors necessary for HIV-1 infection: CD4, CC chemokine receptor 5 (CCR5), and Fcgamma receptors. RESULTS: Human retinal microglia expressed detectable levels of CD4, CD16, CD64, and CCR5 in vitro and Fcgamma receptor I (CD64) in situ. CONCLUSIONS: Human retinal microglia express several candidate receptors required for viral binding and as such may be a potential reservoir for HIV-1 infection.

Adolescent↗
PubMed2003

Expression and distribution of matrix metalloproteinases and their inhibitors in the human iris and ciliary body.

AIM: To determine the expression and distribution of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the normal human iris and ciliary body. METHODS: Seven postmortem human eyes were fixed with formalin. The iris and ciliary body were dissected out and embedded in paraffin. The expression of MMPs -1, 2, 3, and 9, and TIMPs 1-4 in the iris and ciliary body was determined by a novel immunofluorescence technique and the results graded by masked observers. RESULTS: Positive staining for MMPs and TIMPs was observed in all regions of the anterior uvea, and was more intense in the ciliary body than in the iris. Most MMPs and TIMPs showed similar patterns in their distribution. In the ciliary body, staining was strongest in the epithelium, and was localised to the epithelial cell cytoplasm, except for TIMP-3 which was strongly expressed in the basement membranes. In the iris, staining was most noticeable in the anterior border and anterior epithelial layer. Blood vessels in the stroma of the iris and ciliary body also stained moderately for MMPs and TIMPs. CONCLUSION: Both MMPs and TIMPs are widely expressed in the anterior uvea, with a positive correlation between their expressions. Their differential localisation in the ciliary body suggests they may have a role in maintaining homeostasis in the uveal tract.

Aged↗
PubMed2000

Long-term follow-up of trabeculectomy with intraoperative 5-fluorouracil for uveitis-related glaucoma.

PURPOSE: To determine the effect of intraoperative application of 5-fluorouracil (5-FU) on the long-term outcome of trabeculectomy in uveitis-related glaucoma. DESIGN: An open, prospective, noncomparative case study to evaluate the use of intraoperative application for 5 minutes of 25 mg/ml 5-FU in primary trabeculectomy for uveitis-related glaucoma. PARTICIPANTS: Fifty eyes of 43 consecutive patients were enrolled in the study. METHODS: Data were recorded prospectively on specifically designed forms at visits every 3 months after surgery. MAIN OUTCOME MEASURES: The intraocular pressure, need for additional medication, and the need for repeat surgery were the criteria that determined the outcome of surgery. RESULTS: No significant intraoperative, postoperative, or late complications of 5-FU administration were noted. Successful filtration was achieved in 82% of eyes at 1 and 2 years after surgery. The success rate was 67% at 5 years. Failure was significantly more common and occurred earlier in patients of black ethnic origin. No deleterious effect on control of uveitis in relation to surgical intervention was observed. CONCLUSIONS: Intraoperative application of 5-FU appears to be a long-term, safe, and effective adjunct to trabeculectomy in uveitis-related glaucoma.

Adolescent↗
PubMed2000

Susac syndrome: microangiopathy of the retina, cochlea and brain.

BACKGROUND: Susac syndrome is characterized by the triad of branch retinal arterial occlusions, encephalopathy and cochlear microangiopathy. The underlying process is believed to be a small vessel vasculitis causing microinfarcts in the retina, brain and cochlea. METHODS: Analysis of two male and two female cases of Susac syndrome recognized in Australia. RESULTS: In this series the epidemiology, mode of presentation, ophthalmologic features, neurologic and cochleo-vestibular features, radiologic characteristics, cerebrospinal fluid findings, therapeutic interventions, clinical course and outcome of Susac syndrome is examined. Key ophthalmologic differential diagnoses include systemic lupus erythematosis (SLE), Behçet's syndrome and other vasculitides such as sarcoidosis, tuberculosis, syphilis and lymphoma. Neuro-otologic features are most frequently misdiagnosed as multiple sclerosis. CONCLUSION: Susac syndrome, first described in 1979, is becoming an increasingly recognized condition. Early recognition of the syndrome is important because treatment with systemic immunosuppression may minimize permanent cognitive, audiologic and visual sequelae.

Adult↗
PubMed2000

Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells.

PURPOSE: Pterygia are a common, benign, fibrovascular, and infiltrative process of the corneal-conjunctival junction of unknown pathogenesis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes active against all components of the extracellular matrix, whose activity is specifically neutralized by tissue inhibitors of MMPs (TIMPs). In the current study the hypothesis was that MMPs and TIMPs may actively participate in the formation and progression of pterygia. METHODS: In this study, 25 pterygium specimens and 15 normal conjunctival biopsies obtained from subjects undergoing surgery for glaucoma and cataract, were processed for immunohistochemistry or in situ hybridization. Pterygium epithelial cells (PECs) were cultured under serum-free conditions and exposed to proinflammatory cytokines to determine both the mRNA and protein expression profiles of MMPs and TIMPs. RESULTS: Collagenase-1 and gelatinase A were expressed in all pterygia examined, specifically localized to the epithelium (directly adjacent to collagen type III), with gelatinase B expression exclusively associated with neutrophils. No collagenase-1 or gelatinase A was detected in normal conjunctiva. TIMP-1 and -3 were localized to epithelial cells with additional TIMP-3 immunoreactivity detected in the extracellular matrix, endothelial cells and leukocytes of all diseased tissue. TIMP-3 protein was evident in 4 of 15 normal conjunctiva. Induction of collagenase-1, gelatinase A, and TIMP-1 mRNA and protein was demonstrated in epithelial cells treated with tumor necrosis factor-alpha and interleukin-1alpha, whereas TIMP-3 expression was unaltered. CONCLUSIONS: This is the first study to document the cellular expression of MMPs and TIMPs in pterygia and cultured human PECs. MMPs and TIMPs may contribute to the inflammation, tissue remodeling, and angiogenesis that characterize pterygia. Understanding the role these proteins play may lead to novel therapies intended to reduce the progressive nature of pterygia.

Blotting, Western↗
PubMed2000

Behçet's disease in Japan and in Great Britain: a comparative study.

Behçet's disease (BD) is an important cause of visual morbidity throughout the world, but shows striking differences in racial predilection. Despite important advances in the therapeutic management of acute intraocular inflammation, the long-term impact of these new strategies on visual outcome of BD and their efficacy in different ethnic groups is unknown. A comparative study of patient characteristics, clinical ocular features and inflammatory score, and current therapy was undertaken on all patients fulfilling the International Study Group criteria for Behçet's disease and the Behçet's Disease Research Committee of Japan, who attended the Uveitis Clinics of Moorfields Eye Hospital (n=19) and Kurume University School of Medicine (KUS) (n=35) during a continuous consecutive four-week period. Japanese patients were significantly older (43.2+/-11.8 years) than the patients seen in London (35.4+/-8. 9 years). There was a predominance of male patients in both groups. All patients seen in KUS were Japanese, while the patients in London included 12 Caucasians, five Middle Eastern, one African, and one Asian. No significant differences were seen between the two populations in the duration of systemic disease or systems affected by the disease, such as mouth ulcers, genital ulcers, skin lesions including erythema nodosum, or arthritis. The duration of ocular disease was similar in both centres: around seven years. There was, however, a significant difference in the number of eyes with active anterior uveitis (59.7% KUS vs 18.4% London (chi-square: 5.4; p=0.006)) and/or posterior uveitis (31.3% KUS vs 18.4% London (chi-square: 5.42; p<0.02)). No significant differences were found in the number of eyes with optic disc swelling or optic atrophy and in each centre the number of eyes with vision greater than 6/9 or worse than 6/60 were the same. The treatment schedules were very different between the two centres. More patients were treated with topical steroids in Japan (68.7% KUS vs 10.5% London (chi-square: 30.5; p=0.001), but a similar number used concomitant intraocular pressure-lowering agents. More patients received systemic steroids in London (84.2% London vs 17% KUS (chi-square: 20.25; p<0.001)). Three patients received systemic steroids alone, five had prednisolone and cyclosporin, four had prednisolone and azathioprine, and four had triple therapy with prednisolone, cyclosporin, and azathioprine. Only one patient used colchicine. Cyclosporin use was similar in London and KUS (47.4% and 42.8%, respectively). In Japan, three patients used prednisolone alone and three tacrolimus (FK506). In addition, two patients, who were on steroids alone, took colchicine as well. More patients in Japan had undergone surgery for cataract and glaucoma (chi-square: 4.0; p=0.045). In KUS, seven of 67 eyes had cataract surgery. A further three eyes had visually significant cataract and two eyes had undergone glaucoma surgery. In contrast, no patients in London had undergone any surgery up to and including this period.

Administration, Topical↗
PubMed1999

Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis.

OBJECTIVE: To assess the efficacy of ciprofloxacin in the treatment of reactive arthritis (ReA) and anterior uveitis (AU) in a double-blind, randomized, placebo-controlled trial. METHODS: Seventy-two patients participated in this study, 56 with ReA and 42 with AU (26 patients had both ReA and AU). Ciprofloxacin (750 mg twice a day) was administered for 12 months with a 12-month followup. End points of the study included time to disease relapse and measures of disease severity. RESULTS: There was no difference between groups in time to disease relapse, joint inflammation, number of joints and enthesis involved in patients with ReA, or signs and symptoms of AU. CONCLUSION: Long-term treatment of ReA and AU with ciprofloxacin made no statistically significant difference to the natural history of these diseases or their severity.

Anti-Infective Agents↗
PubMed1999

The effect of optic nerve sheath decompression on CSF dynamics in pseudotumour cerebri and related conditions.

The effect of optic nerve sheath decompression (ONSD) on cerebrospinal fluid (CSF) pressure and outflow resistance was studied in six patients who underwent the procedure (four unilateral, two bilateral) for papilloedema secondary to raised intracranial pressure. Four patients (all female, average age 29.3 years) had pseudotumour cerebri while two patients (one male 34 years, one female 24 years) had cryptococcal meningitis. All patients had pre- and postoperative CSF pressure measurements. Three patients had a preoperative CSF infusion study and all six had a postoperative study to measure CSF outflow resistance. Five of the six patients had elevated CSF pressure prior to ONSD and in all five the pressure was still significantly elevated after the procedure. In one symptomatic patient with papilloedema the pressure was normal pre- and post-ONSD (this patient was on acetazolamide). All three patients who tested pre-ONSD had an abnormal outflow resistance; in only one case did this become normal after the procedure, although this patient later required shunting for persistent intracranial hypertension. Clinically, only one of the six cases had a substantial relief of symptoms and signs despite persistently high CSF pressure and outflow resistance. The other five patients went on to shunting after intervals ranging from one week to 8 months. The preliminary conclusion was drawn that ONSD does not have any predictable beneficial effect on CSF pressure or outflow resistance. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Culture and characterisation of epithelial cells from human pterygia.

BACKGROUND/AIMS: Pterygia are a common disorder of the ocular surface. The disease represents a chronic fibrovascular and degenerative process thought to originate at the conjunctival-corneal junction, where altered limbal stem cells are proposed to be the cell of origin. Extensive epidemiological evidence exists to implicate ultraviolet B irradiation in the pathogenesis of pterygia. To date no animal or in vitro culture model has been developed to test such an hypothesis. The aim of this study was to establish and characterise a pure population of epithelial cells derived from pterygium tissue. METHODS: Tissue specimens were obtained from patients undergoing pterygium excision. Explants were cultured in either serum free or serum supplemented medium. Primary and passaged cells were processed for light microscopy, analysed by flow cytometry, and characterised immunohistochemically using specific antibodies. RESULTS: In serum free culture, cuboidal cells with typical morphology of epithelial cells migrated from the pterygium explants from 3 days onwards and eventually formed a cohesive monolayer. Passaged cells consisted of 98.4% cytokeratin positive cells and demonstrated immunoreactivity for multiple cytokeratins, including AE1, AE3, AE5, but were negative for AE8. These cells also expressed an epithelial specific antigen, together with vimentin and mucin, as did epithelial cells in sections of pterygia. CONCLUSIONS: A relatively simple method of isolating pterygium epithelial cells has been established. Cultured pterygium epithelial cells are phenotypically and functionally similar to their in vivo counterparts with respect to keratin, vimentin, and mucin expression. In vitro assays using these cells may aid in elucidating the pathogenesis of pterygia.

Cells, Cultured↗
PubMed1998

Ocular complications of heart, lung, and liver transplantation.

AIM: To document the nature and frequency of ocular complications in a large group of patients who underwent heart, lung, or liver transplantation. METHODS: A retrospective audit of the medical records of all patients undergoing heart, lung, or combined heart-lung transplantation at St Vincent's Hospital, Sydney, or liver transplantation at Royal Prince Alfred Hospital Sydney, was performed to detect patients with symptomatic ocular complications following transplantation. 19 of 860 patients were identified as having ocular complications. RESULTS: Ocular complications occurred in 2% of patients with 65% of these being opportunistic infections. Herpes group viral retinitis (77%) and fungal chorioretinitis (22%) were seen. Other complications included choroidal pseudolymphoma, central retinal vein occlusion, herpes zoster ophthalmicus, herpetic keratitis, dacryocystitis, cyclosporin retinopathy, and rifabutin associated uveitis. CONCLUSION: Herpes group viral retinitis was the most common ocular opportunistic infection and occurred most frequently during the second year after transplantation. Delayed diagnosis was associated with poor visual outcome.

Adult↗
PubMed1997

Increased expression of matrix metalloproteinases in vivo in scleritis tissue and in vitro in cultured human scleral fibroblasts.

Scleritis is a sight-threatening inflammatory disorder of the eye characterized by the degradation of scleral matrix. Matrix metalloproteinases (MMPs) are ubiquitous proteolytic enzymes important in physiological and pathological processes, the activity of which is stringently controlled by the action of a family of natural antagonists, the tissue inhibitors of matrix metalloproteinases (TIMPs). We hypothesized that enhanced expression of MMPs, without the negative regulatory influence of TIMPs, may be a key feature of tissue destruction in inflammatory eye diseases, such as scleritis. The aim of this study was to localize and characterize cells expressing MMPs and TIMPs in sclera affected by necrotizing scleritis and, in a parallel study, to establish whether cytokines modulate MMP expression in cultured human scleral fibroblasts. In situ hybridization and immunohistochemical analyses indicated that resident scleral fibroblasts as well as inflammatory cells such as macrophages and T lymphocytes express stromelysin, gelatinase B, and TIMP-1 in necrotizing scleritis tissue. In addition, cytoplasmic immunoreactivity for tumor necrosis factor-alpha, an inducer of MMPs, was detected in infiltrating inflammatory cells. Cultured scleral fibroblasts stimulated with the combination of interleukin-1 alpha plus tumor necrosis factor-alpha increased TIMP-1 mRNA twofold above constitutive levels. By contrast, these cytokines induced a sevenfold increase in the steady-state levels of stromelysin mRNA. Using Western blotting, stromelysin and TIMP-1 protein production paralleled mRNA induction in cytokine-stimulated human scleral fibroblasts. Culture supernatants harvested from cytokine-stimulated human scleral fibroblasts were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis gelatin substrate zymography. Our results revealed a prominent 92-kd gelatinolytic band corresponding to gelatinase B, which was inducible with interleukin-1 alpha. These data provide evidence for our hypothesis, that an imbalance between enzyme/inhibitor ratios may be the underlying mechanism of the tissue destruction characteristic of scleritis. Our results demonstrate the potential involvement of MMPs and their modulation by cytokines produced by infiltrating inflammatory cells in destructive ocular inflammation.

Adult↗