Sympathetic ophthalmia following severe fungal keratitis.
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Adolescent↗
Biomedical subjects
N P Jones
Publications and source records attributed to N P Jones.
A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe.
AIMS: To examine baseline characteristics of patients recruited into ADOPT, a multinational trial comparing three oral glucose-lowering monotherapies. METHODS: Between April 2000 and June 2002, 4360 patients aged 30-75 years with Type 2 diabetes diagnosed for < 3 years and remaining on diet therapy alone with fasting plasma glucose levels (FPG) between 7.0 and 10.0 mmol/l were enrolled by 488 North American and European centres. Medical histories, anthropometric data and laboratory measurements were determined using common methodologies. RESULTS: The mean (SD) age of the patients was 57 (10) years, body mass index 32.2 (6.4) kg/m(2), HbA(1c) 7.4 (0.9)%; 58% were male, 88% Caucasian and 15% smoked. North American Caucasians (NAC) were younger, more obese, and more insulin resistant than European Caucasians (EUC), but had better pancreatic B-cell function. NAC had lower total, low-density lipoprotein- and high-density liporpotein-cholesterol concentrations with higher triglyceride concentrations and were more often on lipid-lowering treatment. They had lower blood pressure levels but were equally likely to be on antihypertensive treatment. Metabolic syndrome was more frequent and microalbuminuria less frequent in NAC. Within North America, NAC had lower HbA(1c) concentrations than Blacks, Hispanics and Asians despite similar or higher FPG and 30-min postchallenge glucose concentrations. CONCLUSIONS: Caucasian North American and European ADOPT patients differ with respect to adiposity, insulin resistance and metabolic syndrome prevalence. North American Blacks, Hispanics and Asians had lower HbA(1c) concentrations than NAC despite similar or higher glucose concentrations. These phenotypic differences may influence the progression of Type 2 diabetes and the response to initial oral glucose-lowering monotherapy.
Adult↗
Low-dose intraocular triamcinolone injection for intractable macular oedema and inflammation in patients with uveitis.
AIMS: To evaluate the efficacy and safety of low-dose (2 mg in 0.05 ml) intraocular triamcinolone injection for patients with uveitis-related cystoid macular oedema and/or intractable intraocular inflammation. PATIENTS AND METHODS: Retrospective clinical case series. RESULTS: Cystoid macular oedema was eliminated in 24/30 eyes (80%). Intractable intraocular inflammation was eliminated in 4/8 eyes (50%). Snellen visual acuity was improved by two lines or more after 14/36 injections (38.9%). Intraocular pressure rose to above 21 mmHg after 8/36 injections (22%). There were no major complications. CONCLUSIONS: Low-dose (2 mg in 0.05 ml) intraocular triamcinolone acetonide injection is safe and effective for the management of refractory uveitic macular oedema. Its usefulness in controlling inflammation alone is questionable.
Adolescent↗
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol.
AIMS/HYPOTHESIS: Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. MATERIALS AND METHODS: RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1-9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of < or = 7.0%. If confirmed HbA1c rises to > or = 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. RESULTS: Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). CONCLUSIONS/INTERPRETATION: The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.
Blood Glucose↗
Ocular syphilis: the new epidemic.
AIM: To present the clinical presentation, diagnosis, and management of syphilitic uveitis in the context of an epidemic of syphilis in the UK. METHOD: Retrospective clinical case series. RESULTS: Six new cases of syphilitic uveitis presented to the Manchester Uveitis Clinic in 2004, after a 15-fold increase in the incidence of syphilis in the UK, including 615 cases in Greater Manchester in the 5 years to 2004. Four cases had secondary syphilis, two had latent disease, two had no rash, and two were HIV positive. Ocular involvement included anterior or panuveitis, retinitis, retinal vasculitis, and papillitis. All resolved on treatment including intramuscular procaine penicillin G with oral probenecid. CONCLUSIONS: Syphilis is much more common recently and syphilitic uveitis should be considered in all patients with rash and/or headache, where there is retinitis and/or retinal vasculitis, or in any uveitis of uncertain origin. Treatment is that of neurosyphilis.
Adult↗
Long-term results of cataract extraction with intraocular lens implantation in patients with uveitis.
OBJECTIVE: To investigate the long-term visual results after cataract extraction in patients with uveitis, and to demonstrate the long-term viability of intraocular lenses. DESIGN: In all, 61 patients (72 eyes), with update clinical examination, were retrospectively evaluated. Comparison of preoperative, postoperative, and latest visual function including best-corrected Snellen visual acuity, progression of uveitis and its complications, need for postoperative medical or surgical interventions. RESULTS: After a minimum follow-up of 5 years (mean 7 years 7 months), 82% of eyes maintained a visual improvement of two Snellen lines, 74% maintained 6/9 or better, and 14% had 6/18 or worse. The mode acuity was better than 6/6. The prevalence of macular oedema or scarring was 24%, of posterior capsule opacification 96%, and of glaucoma drainage, 15%. CONCLUSIONS: We report the long-term follow-up of cataract extraction and intraocular lens (IOL) implantation performed by a single surgeon on patients with uveitis attending a regional tertiary referral uveitis clinic. Using stringent perioperative and postoperative control of inflammation, patients with uveitis usually maintain high visual acuity over long-term follow-up. The incidence of sight-threatening postoperative complications is low and no ongoing complication has been attributed to IOL implantation.
Adolescent↗
Frosted branch angiitis: a review.
The purpose of this study is to present the first report of a case of primary frosted branch angiitis from the UK and to review the characteristics of this rare disease. Primary frosted branch angiitis causes characteristic florid translucent retinal perivascular sheathing of both arterioles and venules in association with variable uveitis, retinal oedema and visual loss, normally with good recovery. A total of 57 cases have been reported in the world literature. Atypical, typically focal frosted branch angiitis may also occur secondary to other causes of intraocular inflammation, especially cytomegalovirus retinitis. Primary frosted branch angiitis has a characteristic presentation but a variable course, typically affecting children or young adults. The disease is likely to represent a common immune pathway in response to multiple infective agents. The optimal treatment is unclear.
Age Distribution↗
Uveitis and the menstrual cycle.
PURPOSE: To establish whether there is a variation in the incidence of onset of acute anterior uveitis (AAU) in women during the phases of the menstrual cycle. METHODS: Prospective open study in women attending the Acute Referral Centre with a first or recurrent attack of AAU. RESULTS: There was a significant increase in the incidence of AAU during the late stages of the menstrual cycle. CONCLUSIONS: The onset of AAU is partially dependent on the levels of either oestrogen or progesterone, or both. The withdrawal of the proven anti-inflammatory effects of these hormones may provoke the onset of uveitis.
Acute Disease↗
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.
AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.
Adult↗
Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.
AIM: These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2DM) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2DM who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue. METHODS: Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2DM patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm(-2), 25-30 kgm(-2), >30 kgm(-2) respectively). RESULTS: RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: -16% and +19%; 8 mg: -37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese. CONCLUSIONS: In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.
Adult↗
Secondary posterior chamber intraocular lens implantation in Fuchs' heterochromic uveitis.
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Adult↗
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↗
Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling.
Phospholipase Cgamma (PLCgamma) isoforms are regulated through activation of tyrosine kinase-linked receptors. The importance of growth factor-stimulated phosphorylation of specific tyrosine residues has been documented for PLCgamma1; however, despite the critical importance of PLCgamma2 in B-cell signal transduction, neither the tyrosine kinase(s) that directly phosphorylate PLCgamma2 nor the sites in PLCgamma2 that become phosphorylated after stimulation are known. By measuring the ability of human PLCgamma2 to restore calcium responses to the B-cell receptor stimulation or oxidative stress in a B-cell line (DT40) deficient in PLCgamma2, we have demonstrated that two tyrosine residues, Tyr(753) and Tyr(759), were important for the PLCgamma2 signaling function. Furthermore, the double mutation Y753F/Y759F in PLCgamma2 resulted in a loss of tyrosine phosphorylation in stimulated DT40 cells. Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2. Further analysis of PLCgamma2 tyrosine residues phosphorylated by Btk and several kinases from the Src family has suggested multiple sites of phosphorylation and, in the context of a peptide incorporating residues Tyr(753) and Tyr(759), shown preferential phosphorylation of Tyr(753).
Agammaglobulinaemia Tyrosine Kinase↗
Phacoemulsification with intraocular lens implantation in patients with uveitis.
PURPOSE: To investigate the safety and efficacy of phacoemulsification with intraocular lens implantation in eyes affected by uveitis. METHODS: A retrospective case series is presented including casenote review and update patient examinations. Patient data were withdrawn from the Uveitis Clinic database. All uveitis patients undergoing phacoemulsification with intraocular lens implantation from August 1995 to November 2000 were included. A pre-operative preparation protocol was used. Operative and post-operative complications, degree of postoperative inflammation, best-corrected and final visual acuity were the main outcome measures. RESULTS: Eighty-six eyes of 75 patients underwent surgery, which in 11 cases was combined with trabeculectomy. Mean follow-up was 24.1 months. Eight eyes (10%) had severe or fibrinous uveitis post-operatively. The mean delay between surgery and return to baseline treatment was 8.6 weeks. Posterior capsule opacification occurred in 42% of eyes and Nd-YAG capsulotomy was required in 21%. Cystoid macular oedema was seen in 2 eyes. Seventy-two per cent of eyes retain a visual acuity of 6/9 or better, and 87% of eyes retain a post-operative improvement of 2 or more lines of Snellen acuity. CONCLUSIONS: With careful patient selection, appropriate pre-operative preparation, diligent surgery and close post-operative supervision, phacoemulsification with intraocular lens implantation is safe and effective in the great majority of eyes with uveitis.
Administration, Topical↗
Antifungal activity of extracts from medicinal plants used by First Nations Peoples of eastern Canada.
From literature describing medicinal usage of plants by First Nations Peoples in eastern Canada, 18 eastern Canadian plants were selected and tested for their antifungal activities. Eight randomly selected tropical plants were also tested for comparative purposes. Four groups of plants were obtained: popular antimicrobial-remedy (n=6), popular non-antimicrobial-remedy (n=6), random temperate (n=6) and random tropical (n=8). Extracts from these plants were tested in disk assays as growth inhibitors of six fungi known to be opportunistic human pathogens (Saccharomyces cerevisiae, Cryptococcus neoformans, Candida albicans, Aspergillus fumigatus, Microsporum gypseum and Trichophyton mentagrophytes). Of the four plant groups tested, extracts from the popular antimicrobial-remedy group were significantly more effective at inhibiting fungal growth based on both overall antifungal activity and number of fungal species inhibited.
Antifungal Agents↗
Vitrectomy for vitreous opacification in Fuchs' heterochromic uveitis.
PURPOSE: To assess the role of pars plana vitrectomy (PPV) for symptomatic vitreous opacification in a series of patients with Fuchs' heterochromic uveitis (FHU). METHODS: A retrospective review was undertaken of 13 patients with FHU who underwent vitrectomy for vitreous opacification between April 1989 and December 1998. RESULTS: An improvement in visual symptoms was recorded in all patients, 9 of 13 (69%) demonstrating at least a 2 line increase in Snellen visual acuity. All but one patient attained 6/9 or better visual acuity post-operatively. Surgery was uneventful and did not appear to exacerbate any existing intraocular inflammation. CONCLUSION: From this series we conclude that PPV has an important role in the management of patients with FHU who present with symptomatic vitreous opacification.
Adult↗
Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients.
AIMS: This study was designed to test the efficacy and safety of low-dose rosiglitazone, a potent, insulin-sensitizing thiazolidinedione, in combination with sulphonylurea in Type 2 diabetic patients. METHODS: For the intention-to-treat analysis, 574 patients (59% male, mean age 61 years) were available, randomized to receive 26 weeks of twice-daily placebo (n = 192), rosiglitazone 1 mg (n = 199) or rosiglitazone 2 mg (n = 183) in addition to existing sulphonylurea treatment with gliclazide (47.6% of patients), glibenclamide (41.8%) or glipizide (9.4%) (two patients were taking carbutamide or glimepiride). Change in haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fructosamine, insulin, C-peptide, albumin, and lipids were measured, and safety was evaluated. RESULTS: Mean baseline HbA1c was 9.2% and FPG was 11.4 mmol/l. Rosiglitazone at doses of 1 and 2 mg b.d. plus sulphonylurea produced significant decreases, compared with sulphonylurea plus placebo, in HbA1c (-0.59% and -1.03%, respectively; both P<0.0001) and FPG (1.35 mmol/l and 2.44 mmol/l, respectively; both P<0.0001). Both HDL-cholesterol and LDL-cholesterol increased and potentially beneficial decreases in non-esterified fatty acids and gamma glutamyl transpeptidase levels were seen in both rosiglitazone groups. The overall incidence of adverse experiences was similar in all three treatment groups, with no significant cardiac events, hypoglycaemia or hepatotoxicity. CONCLUSIONS: Overall, the combination of rosiglitazone and a sulphonylurea was safe, well tolerated and effective in patients with Type 2 diabetes.
Adult↗
Rosiglitazone taken once daily provides effective glycaemic control in patients with Type 2 diabetes mellitus.
AIMS: To evaluate the clinical efficacy and safety of rosiglitazone as a once daily treatment for Type 2 diabetes mellitus (DM). METHODS: Three hundred and sixty-nine patients with Type 2 DM (mean age 63 years; mean body mass index (BMI) 29.4 kg/m2) were enrolled in a double-blind, parallel group, placebo-controlled, dose-ranging study. Patients were randomly assigned to receive placebo or rosiglitazone at doses of 4, 8, or 12 mg daily for 8 weeks. RESULTS: At 8 weeks, fasting plasma glucose (FPG) decreased significantly in the rosiglitazone 4 mg, 8 mg, and 12 mg groups (-0.9, -2.0 and -1.7 mmol/l; P = 0.0003, < 0.0001, and < 0.0001, respectively) compared with placebo (+0.4 mmol/l). The improvements in FPG were dose ordered for 4 and 8 mg/ day. The 12 mg/day dose produced no additional improvement. There were small decreases in haemoglobin and haematocrit in the rosiglitazone treatment groups. The overall incidence of adverse experiences was similar in all treatment groups, including placebo with no evidence of hypoglycaemia or hepatotoxicity. CONCLUSIONS: Rosiglitazone improves glycaemic control when given once daily to treat Type 2 diabetes mellitus and is well tolerated at doses up to and including 12 mg.
Adult↗