PubMed Health⌕ Search

Biomedical subjects

P I Murray

Publications and source records attributed to P I Murray.

At least 19 recordsLinked to original sources
PubMed2003

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension.

BACKGROUND: Intraocular pressure (IOP) is maintained by a balance between aqueous humour (AH) production (dependent on sodium transport across a ciliary epithelial bi-layer) and drainage (predominantly through the trabecular meshwork). In peripheral epithelial tissues, sodium and water transport is regulated by corticosteroids and the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes (11beta-HSD1 activating cortisol from cortisone, 11beta-HSD2 inactivating cortisol to cortisone). AIM: To analyse expression of 11beta-HSD in the human eye and investigate its putative role in AH formation. DESIGN: Multipart prospective study, including a randomized controlled clinical trial. METHODS: The expression of 11beta-HSD1 in normal human anterior segments was evaluated by in situ hybridization (ISH). RT-PCR for 11beta-HSDs, glucocorticoid and mineralocorticoid receptors (GR, MR) was performed on human ciliary body tissue. AH cortisol and cortisone concentrations were measured by radioimmunoassay on specimens taken from patients with primary open-angle glaucoma (POAG) and age-matched controls. Randomized, placebo-controlled studies of healthy volunteers and patients with ocular hypertension (OHT, raised IOP but no optic neuropathy) assessed the effect of oral carbenoxolone (CBX, an inhibitor of 11beta-HSD) on IOP. RESULTS: ISH defined expression of 11beta-HSD1 in the ciliary epithelium, while RT-PCR analysis of ciliary body tissue confirmed expression of 11beta-HSD1, with additional GR and MR, but not 11beta-HSD2 expression. In both POAG patients and controls, AH concentrations of cortisol exceeded those of cortisone. The CBX-treated healthy volunteers who demonstrated the largest change in urinary cortisol metabolites, indicative of 11beta-HSD1 inhibition, had the greatest fall in IOP. Patients with OHT showed an overall reduction of IOP by 10% following CBX administration, compared to baseline (p<0.0001). DISCUSSION: CBX lowers IOP in patients with ocular hypertension. Our data suggest that this is mediated through inhibition of 11beta-HSD1 in the ciliary epithelium. Selective and topical inhibitors of 11beta-HSD1 could provide a novel treatment for patients with glaucoma.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2003

A prospective study of the rate of falls before and after cataract surgery.

BACKGROUND: There has been considerable interest in the development of intervention programmes aimed at reducing the risk of falls. The primary objective was to ascertain whether cataract surgery reduced the risk of falls in elderly patients with age related cataract. METHODS: 97 patients scheduled for cataract surgery were enrolled in this prospective clinical study. The patients were assessed for established risk factors for falls preoperatively and postoperatively. Patients were issued with a diary to record any falls and phoned at 2 monthly intervals during the 6 month preoperative and postoperative periods. RESULTS: Of the 84 patients who completed the study, 31 recorded falls during the preoperative period (37%). This group showed a statistically significant reduction in the number of fallers in the postoperative period (n = 6, p<0.001) CONCLUSION: These results suggest that cataract surgery is an effective intervention to reduce the risk of falls in elderly patients with cataract related visual impairment.

Accidental Falls↗
PubMed2002

Corticosteroid-induced osteoporosis in patients with uveitis.

AIMS: To estimate the prevalence of low bone density and osteoporosis in a population of patients with uveitis taking systemic steroid treatment; to clarify the risks of steroid-induced fracture and to suggest a protocol for the prevention and management of bone loss in patients with ophthalmic inflammatory disease. METHODS: Bone densitometry was performed on 129 adult patients with prednisolone-treated uveitis from four centres. Information on uveitis diagnosis, associated risk factors, steroid dosage and treatment duration, prophylaxis and management, was collected. Juveniles, patients with scleritis and those who had used deflazacort, were excluded. RESULTS: Steroid treatment time varied from 13 weeks to 31 years, and the total dosage from 1.29 g to 166.5 g. Twenty-six percent of patients also used one or more immunosuppressives. Forty-eight percent had additional risk factors for bone loss. Bone density was abnormally low in 44.2%, and 15.5% had osteoporosis. Osteoporosis was substantially more common in males (20.6%, all under 60 yrs) than in females (9.8%). Seven symptomatic fractures occurred in patients on treatment. Bone loss correlated with total steroid dose, mean dose, duration of treatment and the presence of pre-existing risk factors. CONCLUSIONS: The prevalence of steroid-induced osteoporosis and fracture is low for patients with uveitis but young males are at risk. Patients at high risk should be identified, and prophylaxis and treatment should be used as required. The guideline of the National Osteoporosis Society is recommended as a management protocol.

Adult↗
PubMed2002

Unilateral varicella zoster virus ophthalmicus and contralateral acute retinal necrosis.

We report two patients who developed varicella zoster virus (VZV) ophthalmicus complicated by ipsilateral keratouveitis, and within 4 weeks developed acute retinal necrosis (ARN) in the contralateral eye. The ipsilateral retina was spared in each case. One patient had systemic lupus erythematosus (SLE) and the other Hodgkin's disease. Both patients were in remission at the time of presentation.

Adult↗
PubMed2002

Correlation between visual function and visual ability in patients with uveitis.

AIM: To investigate the correlation between tests of visual function and perceived visual ability recorded with a quality of life questionnaire for patients with uveitis. METHODS: 132 patients with various types of uveitis were studied. High (monocular and binocular) and low (binocular) contrast logMAR letter acuities were recorded using a Bailey-Lovie chart. Contrast sensitivity (binocular) was determined using a Pelli-Robson chart. Vision related quality of life was assessed using the Vision Specific Quality of Life (VQOL) questionnaire. RESULTS: VQOL declined with reduced performance on the following tests: binocular high contrast visual acuity (p = 0.0011), high contrast visual acuity of the better eye (p = 0.0012), contrast sensitivity (p = 0.005), binocular low contrast visual acuity (p = 0.0065), and high contrast visual acuity of the worse eye (p = 0.015). Stepwise multiple regression analysis revealed binocular high contrast visual acuity (p <0.01) to be the only visual function adequate to predict VQOL. The age of the patient was also significantly associated with perceived visual ability (p <0.001). CONCLUSIONS: Binocular high contrast visual acuity is a good measure of how uveitis patients perform in real life situations. Vision quality of life is worst in younger patients with poor binocular visual acuity.

Adolescent↗
PubMed2001

Uveitis with autoimmune hepatic disorders.

Many cases of uveitis are thought to be autoimmune in nature. We report two cases of panuveitis, one of which was associated with chronic active hepatitis and the other with primary biliary cirrhosis. This suggests that the autoimmune disturbance may have been responsible for the development of the intraocular inflammation.

Administration, Oral↗
PubMed2001

Expression and putative role of 11 beta-hydroxysteroid dehydrogenase isozymes within the human eye.

PURPOSE: The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes: an oxo-reductase (11 beta-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase (11 beta-HSD2) that inactivates F to E. The purpose of this study was to analyze the expression and putative role of 11 beta-HSD within the human eye. METHODS: Immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed on sections of human ocular tissues, surgical trabecular meshwork (TM) specimens and a ciliary nonpigmented epithelial (NPE) cell-line. Free F and E concentrations in aqueous humor were determined by gas chromatography-mass spectrometry (GC/MS). IOP was measured in eight male volunteers before and after oral ingestion of carbenoxolone (CBX), a known inhibitor of 11 beta-HSD. RESULTS: 11 beta-HSD1 was expressed in the basal cells of the corneal epithelium and the NPE. 11 beta-HSD2 was restricted to the corneal endothelium. RT-PCR revealed mRNA for only the glucocorticoid receptor (GR) in the TM specimens, whereas GR, mineralocorticoid receptor and 11 beta-HSD1 mRNAs were all present in the NPE cell line. The demonstration of free F in excess of E (F/E 14:1) in the aqueous humor suggested predominant 11 beta-HSD1 activity. Compared with baseline (14.7 +/- 1.06 mm Hg, mean +/- SD), the IOP decreased significantly on both the third and seventh days of CBX ingestion (12.48 +/- 1.11 mm Hg, P < 0.0001 and 11.78 +/- 1.50 mm Hg, P < 0.0001, respectively). CONCLUSIONS: These results suggest that the 11 beta-HSD1 isozyme may modulate steroid-regulated sodium transport across the NPE, thereby influencing IOP.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Virus-directed, enzyme prodrug therapy with nitroimidazole reductase: a phase I and pharmacokinetic study of its prodrug, CB1954.

CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] is converted by the bacterial enzyme nitroimidazole reductase (NTR) into a potent cytotoxic bifunctional alkylating agent, which can be delivered to tumors in adenoviral vectors as virus-directed, enzyme prodrug therapy. This report summarizes a Phase I and pharmacokinetic study of the prodrug, CB1954. Thirty patients, ages 23-78 years (median 62 years), with predominantly gastrointestinal malignancies were treated. CB1954 was administered by i.v. injection every 3 weeks or i.p. followed by 3-weekly i.v. injections, toward a maximum of six cycles. The dose was escalated from 3 to 37.5 mg/m2. No significant toxicity was seen until 24 mg/m2 (recommended i.v. dose). Dose-limiting toxicities (DLT) were diarrhea and hepatic toxicity, seen at 37.5 mg/m2. DLT has not been observed at the current i.p. dose of 24 mg/m2. There was no alopecia, marrow suppression, or nephrotoxicity. Clearance data suggest hepatic metabolism, and <5% of CB1954 was renally excreted. There was a nonlinear relationship between i.v. dose and area under the curve (AUC). At the recommended i.v. dose of 24 mg/m2, the AUC was 5.8 microM/h. Intraperitoneal administration (24 mg/m2) achieved an AUC of 387 microM/h, giving a considerable regional advantage. In vitro, the AUC required to achieve the IC50 for CB1954, in NTR-expressing cancer cells, ranges from 10-50 microM/h. Thus, CB1954 is well tolerated at a dose of 24 mg/m2, and sufficient serum/peritoneal levels are achieved for an enzyme-prodrug approach to be feasible. We are now conducting a Phase I trial combining adenovirus-mediated NTR and i.v. CB1954 (24 mg/m2) in patients with primary and secondary liver tumors.

Abdominal Pain↗
PubMed2000

Labial adenocarcinoma after treatment with cyclosporin a in a patient with panuveitis.

PURPOSE: To report a case of labial basal cell adenocarcinoma in a patient with uveitis on treatment with cyclosporin A. METHOD: Case report. A 73-year-old woman with panuveitis and retinal vasculitis presented with a lump on her lip after 52 months of treatment with cyclosporin A. RESULT: Excision biopsy showed a labial adenocarcinoma. CONCLUSION: Malignancy can occur after long-term cyclosporin A treatment for uveitis.

Adenocarcinoma↗
PubMed2000

Evaluation of foldable intraocular lenses in patients with uveitis.

OBJECTIVE: To evaluate various foldable posterior chamber intraocular lenses (IOLs) after phacoemulsification in patients with uveitis. DESIGN: A prospective, noncomparative, interventional case series. PARTICIPANTS: Forty-nine consecutive patients (60 eyes) with various types of uveitis (anterior, n = 20; posterior, n = 1; panuveitis, n = 37, intermediate, n = 2). INTERVENTION: All patients underwent phacoemulsification with foldable posterior chamber IOL implantation. All eyes were free of active inflammation at the time of surgery. A variety of IOL biomaterials were implanted: acrylic (n = 30), silicone (n = 17), and hydrogel (n = 13). MAIN OUTCOME MEASURES: Detailed examination was performed by one masked observer. Several parameters were compared for each implant biomaterial, including level of best corrected Snellen visual acuity at final follow-up, presence of posterior synechiae, anterior capsular phimosis, posterior capsule opacification, and the degree of cellular deposits on the IOL optic. RESULTS: There were 26 males and 23 females, aged 9 to 83 years (mean, 48 years). Follow-up ranged from 1 to 33 months (mean, 17.03 months). At final follow-up, 56 eyes (93.3%) had an improvement in visual acuity compared with preoperative levels as follows: 34 eyes (56.6%) achieved an improvement of four or more Snellen lines, and 44 eyes (73.3%) achieved 20/30 or better. Giant cells, observed on the IOL optic in 19 eyes (31.7%), were most often seen on the acrylic biomaterial at the 1-month follow-up, although this was not found to be statistically significant. Scratch marks produced by the lens-introducing forceps were seen in 24 eyes (40.0%), mainly on the acrylic and hydrogel optics. Posterior capsule opacification (PCO) occurred in 49 eyes (81.7%), with only 5 eyes requiring laser capsulotomy. There was no association between PCO and the various lens biomaterials. Other causes for reduced visual acuity included glaucomatous optic neuropathy (n = 5) and cystoid macular edema (n = 8). CONCLUSIONS: The use of foldable IOLs in eyes with uveitis is safe, but the optimal biomaterial has yet to be found.

Acrylic Resins↗
PubMed2000

Deep intramuscular methylprednisolone for the treatment of cystoid macular oedema in uveitis.

PURPOSE: To study the use of intramuscular methylprednisolone in the treatment of cystoid macular oedema in patients with uveitis. METHODS: A total of 32 patients with various types of uveitis with unilateral cystoid macular oedema were recruited. Patients received 160 mg of intramuscular methylprednisolone into the thigh and were reassessed 6-8 weeks later. In 17 patients in whom there had been no significant improvement, a further injection of methylprednisolone was given; a total of 49 injections. RESULTS: After a first injection a significant improvement in vision (an increase of > or = 2 Snellen lines) was seen in 15 of 32 eyes (47%), and 17 of 32 eyes (53%) showed no significant change. After the second injection 7 of 17 eyes (41%) showed a significant improvement but there was no change in 9 of 17 eyes (53%). Only one eye deteriorated more than 2 lines of Snellen acuity. There were minimal ocular or systemic side effects associated with this form of treatment. CONCLUSIONS: Despite limited success, deep intramuscular methylprednisolone may have a role as an alternative mode of treatment in uveitis patients with unilateral cystoid macular oedema, thus avoiding the potential hazards of periocular injections. In comparison with orally administered systemic corticosteroids, an injection ensures patient compliance and is associated with fewer side effects.

Adolescent↗