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Biomedical subjects

A R Rudnicka

Publications and source records attributed to A R Rudnicka.

15 recordsLinked to original sources

Associations of plasma fibrinogen and factor VII clotting activity with coronary heart disease and stroke: prospective cohort study from the screening phase of the Thrombosis Prevention Trial.

BACKGROUND: As with 'conventional' risk factors such as cholesterol and smoking, there is a need for large, long-term prospective studies on hemostatic factors. OBJECTIVES: To investigate the prospective relationship of fibrinogen and factor VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and stroke in a study with a large number of outcomes over a period of 15 years. PATIENTS/METHODS: A cohort of 22 715 men aged 45-69 years was screened for participation in the Thrombosis Prevention Trial. Men were followed up for fatal and non-fatal CHD and stroke events. There were 1515 CHD events (933 CHD deaths) and 391 strokes (180 stroke deaths). Hazard ratios (HRs) and 95% confidence intervals are expressed per standardized increase in log fibrinogen and log FVIIc, adjusting for age, trial treatment group, conventional CHD risk factors and regression dilution bias. RESULTS: Hazard ratios for fibrinogen were 1.52 (1.37-1.70) for all CHD events, and 1.36 (1.09-1.69) for all strokes. Exclusion of events within the first 10 years showed a persistent association between CHD and fibrinogen, with an adjusted HR of 1.93 (1.42-2.64). The HRs for FVIIc, adjusting for age and trial treatment, were 1.07 (1.01-1.12) for all CHD events and 1.07 (0.97-1.20) for all strokes, and the fully adjusted HRs were, respectively, 0.97 (0.84-1.05) and 1.07 (0.85-1.33). CONCLUSIONS: The persisting association between fibrinogen and CHD beyond 10 years may imply a causal effect. There is a small effect of FVIIc on CHD, after adjustment for age and trial treatment, but no association independent of other risk factors.

Age Factors↗

Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.

OBJECTIVES: To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment. DESIGN: Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke. MAIN OUTCOME MEASURES: Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol. RESULTS: Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P < 0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded (P < 0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce IHD events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Estimates allow for the fact that trials tended to recruit people with vascular disease, among whom the effect of LDL cholesterol reduction on stroke is greater because of their higher risk of thromboembolic stroke (rather than haemorrhagic stroke) compared with people in the general population. CONCLUSIONS: Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.

Cholesterol, LDL↗

How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom?

AIMS: To predict the burden of blindness, partial sight, and visual impairment (binocular visual acuity 6/18 or less) due to late stage age related macular degeneration (AMD) in the ageing population of the United Kingdom. METHODS: A systematic review, followed by a request for data, was used to establish a pooled prevalence of AMD and corresponding visual loss. Prevalence figures were applied to the UK population. Using UK population trends, the future burden of AMD over the coming decade was established. RESULTS: Pooled data from six studies showed that the prevalence of visual loss caused by AMD increased exponentially from the age of 70-85 years of age, with 3.5% (95% CI 3.0 to 4.1) having visual impairment beyond the age of 75 years. The authors estimate that there are currently 214 000 (95% CI 151 000 to 310 000) with visual impairment caused by AMD (suitable for registration). This number is expected to increase to 239 000 (95% CI 168 000 to 346 000) by the year 2011. Currently there are 172 000 (95% CI 106 000 to 279 000) and 245 000 (95% CI 163 000 to 364 000) with geographical and neovascular AMD, respectively. CONCLUSIONS: Estimates of visual impairment agree with official statistics for the number registered partially sighted or blind, caused by AMD, and are well below other figures often cited. Although these estimates are associated with wide confidence intervals (CI) and a number of caveats, they represent the best available data, which can be used to guide health and social care provision for older people in the UK setting. Implications for low vision services are outlined.

Age Distribution↗

An association between plasma free protein s concentration and risk of coronary heart disease in middle-aged men.

Protein S is a vitamin K-dependent protein with anticoagulant properties. Case series have reported reduced plasma concentrations in patients with arterial thromboses, while other studies have reported increased levels in patients with coronary heart disease (CHD). The present study sought to clarify the relation between free protein S and risk of CHD. A prospective survey was conducted of 3000 men aged 50 to 61 years, free of clinical CHD at baseline. Free protein S was measured by commercial immunoassay. End-points recorded were sudden coronary death, first nonfatal and fatal myocardial infarction (MI), surgical intervention for symptomatic, angiographically demonstrated CHD, and all-causes mortality. Statistical analysis employed univariate incidence rate ratios followed by Cox proportional hazards regression. There were 168 CHD events recorded during 21,000 person-years of risk. Mean free protein S concentration was 6% higher in those who developed CHD than in the remainder, the crude hazard ratio (HR) for a one standard deviation (S.D.) increase in free protein S being 1.25 (95% CI, 1.08-1.25). Free protein S was associated with cholesterol concentration and other conventional CHD risk factors. In multivariate regression analysis, after adjustment for conventional CHD risk factors a 1 S.D. increase in free protein S was associated with a HR of 1.15 (0.98-1.35) for CHD, of borderline conventional statistical significance. This association of free protein S with risk of CHD may reflect effects of plaque-destabilising inflammatory activity on protein S levels.

Analysis of Variance↗

Nonlinear behavior of certain optic nerve head parameters and their determinants in normal subjects.

OBJECTIVE: To investigate the relationship between the absolute area of certain optic disc parameters and a number of ocular dimensional characteristics and demographic factors in young, healthy subjects. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred twenty-one subjects, aged 16.5 to 35.4 years participated, encompassing a wide range of refractive error from +4 diopters (D) to -25.75 D. One eye from each subject was randomly selected for examination. MAIN OUTCOME MEASURES: Absolute size of the optic disc parameters: optic disc area (DA), neuroretinal rim area (NRA), optic cup area (CA), and peripapillary atrophy area (PA). METHODS: Absolute sizes of optic disc parameters were determined from digitized photographic color transparencies, taking into consideration the magnification of the fundus camera and human eye. Relationships between the absolute size of the optic disc features and axial length, crystalline lens thickness, anterior chamber depth, ocular refraction, front surface keratometry, age, and gender were examined. RESULTS: Axial length, lens thickness, front surface keratometry, and age demonstrated positive associations with all optic disc parameters, and anterior chamber depth and ocular refraction demonstrated negative associations in all cases. Multiple regression analysis revealed that the associations observed univariately for age, anterior chamber depth, lens thickness, front surface keratometry, and ocular refraction were confounded by axial length for all disc parameters. After taking logs, DA and NRA exhibit an exponential relationship with axial length, whereas PA and CA exhibit a linear relationship with axial length. DA and NRA increase by approximately 3% per millimeter increase in axial length at 20 mm and up to 40% for DA and 50% for NRA at an axial length of 35 mm. PA and CA are estimated to increase by 26% (10%-44%) and 10% (5%-16%), respectively, per millimeter increase in axial length. Females have approximately 5% smaller DA and 7% smaller NRA than males, but these effects are not statistically significant (P > 0.2). From the multiple regression analysis, females have 31% larger optic cup areas (1%-57%, P = 0.03) and 24% smaller PA (42% smaller to 5% larger P = 0.06) than males, but these effects are of borderline statistical significance at 5%. CONCLUSIONS: Of the ocular biometric factors considered, axial length seems to be the most important predictor of the absolute area of the optic disc parameters. No association exists between any disc parameter and age in this sample of subjects less than 40 years of age. Females exhibited smaller values for DA, NRA, and PA than did males, differences that were not statistically significant, and larger CA (P = 0.03).

Adolescent↗

A randomized controlled trial of the antiemetic effect of three doses of ondansetron after strabismus surgery in children.

METHODS: One hundred and thirty-one healthy children, aged 31-152 months, undergoing strabismus surgery under general anaesthesia, were randomly allocated to one of four groups: group A received 0.04 mg.kg-1 ( identical with 1 mg.m-2) of ondansetron, group B 0.1 mg.kg-1 ( identical with 2.5 mg.m-2), group C 0.2 mg.kg-1 ( identical with 5 mg.m-2) and group D placebo, given intravenously following induction of anaesthesia. Morphine 0.15 mg.kg-1 was given intravenously, intraoperatively, to provide postoperative analgesia. Hourly records of emetic episodes were made for 24 h. RESULTS: A considerably higher proportion of children suffered emesis in the placebo group compared to the active treatment groups taken together, during the first 8 h of postoperative care (76% vs. 45%, P=0.002). During the first 8 h, only 25% of those in treatment group C suffered emesis, the number-needed-to-treat was 3. There was a statistically significant decrease in the chance of vomiting with increasing dose of ondansetron (P=0.03). By 24 h, the difference in the rate of emesis was less marked but still statistically significant (90% vs. 69%, P=0.03). CONCLUSION: Overall, children given ondansetron had less than one-half the risk of vomiting compared to those given placebo (hazard ratio 0.46, 95% confidence interval 0.29-0.74). The mean number of emetic episodes declined from 2.73 in the placebo group to 1.92 in treatment group C. There was no difference in the incidence of side-effects between groups.

Antiemetics↗

Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and LogMAR acuity.

BACKGROUND: A study was carried out to ascertain, in ophthalmologically normal subjects, the short-term effects of dipivefrin hydrochloride 0.1% on visual performance and make comparisons with pilocarpine. METHODS: Twelve normal volunteers aged 20-26 years attended on three occasions. One eye, randomly selected, received one drop of either pilocarpine 2%, dipivefrin or saline 0.9%. High- and low-contrast LogMAR acuity at 6 m and pupil diameter (measured by infra-red pupillometry) were recorded at baseline (T0) and at intervals up to 90 min following instillation of drops. Program 30-2 of the Humphrey Visual Field Analyzer (HFA) was run at T0 and at 60 min after treatment instillation (T60). Saline was always instilled at visit 1, to allow for learning effects. On visits 2 and 3 either pilocarpine or dipivefrin was randomly instilled into the treated eye. RESULTS: Pilocarpine significantly worsened the field global indices mean deviation (P < 0.001) and pattern standard deviation (P < 0.01) compared with T0. There was no significant change with dipivefrin. A significant (P = 0.01) pupil dilation from 5.44 mm (SD 0.79) at T0 to 6.19 mm (SD 1.09) at T90 occurred with dipivefrin. Pilocarpine caused significant miosis. No significant changes in LogMAR values were found with dipivefrin. Pilocarpine significantly (P < 0.01) increased LogMAR values (i.e. reduced acuity) compared with dipivefrin. At T30 the mean increase in LogMAR was 0.76 (SD 0.30) for high and 0.83 (SD 0.11) for low contrast. By T90 recovery of acuity was virtually complete. CONCLUSIONS: In normals dipivefrin causes mydriasis but does not affect the central visual field global indices (as assessed by STATPAC), or high- and low-contrast LogMAR acuity. Pilocarpine adversely affects the visual field and both measures of acuity. Knowledge of these effects is of value in glaucoma therapy and when monitoring the progression of visual loss.

Adult↗

Magnification characteristics of fundus imaging systems.

OBJECTIVE: To compare the magnification properties of 11 different fundus cameras (including 1 stereo fundus camera), a Rodenstock (infrared) scanning laser ophthalmoscope (SLO), the Heidelberg Laser Tomographic Scanner (LTS), and the Heidelberg Retina Tomograph (HRT). DESIGN: A cross-sectional study of the relationship between the true size of a fundus feature and its photographic-computer image in 14 different fundus imaging devices. This relationship was evaluated for each instrument using a model eye adjusted for axial ametropia between +11 diopter (D) and -14 D. To simulate refractive ametropia, the "crystalline lens" was removed to render the model eye aphakic, and the axial length was adjusted to give aphakic ametropia from emmetropia to +20 D. MAIN OUTCOME MEASURES: A correction factor (p) was calculated for each instrument, which can be used in calculations for determining true retinal size. RESULTS: The following were found to be of telecentric construction, Zeiss Oberkochen (WS240 Heidelberg), Zeiss Oberkochen (UK), Zeiss Oberkochen (Cologne), Nikon NF505, Kowa RCXV, SLO prototype (UK), LTS, and the HRT, and each exhibited a constant relationship between p and degree of ametropia of the model eye. The Canon CF6OU, Canon CF6OS, Canon CR4-45NM, Nidek 3-DX, Olympus GRCW, and Carl Zeiss Jena Retinophot were found not to be telecentric and exhibited a linear relationship between p and degree of ametropia of the model eye. For all instruments, p remained unchanged for axial and refractive ametropias of the same degree. CONCLUSIONS: The study has shown that not all fundus imaging systems are telecentric, so the use of a single magnification correction value may not be appropriate. These findings have important implications for the way in which true retinal size calculations are performed. Examples are given to show how the tabulated values of correction factors can be used for both telecentric and nontelecentric cameras in image size calculations.

Fundus Oculi↗

Measurement of optic disc size: equivalence of methods to correct for ocular magnification.

AIMS: To compare methods available to correct the magnification of images that result from the optics of the eye and identify errors, and source of error, of the methods. METHODS: 11 methods were applied to ocular biometry data from three independent cohorts. Each method was compared with the method of Bennett, which uses most biometric data. The difference between each method and Bennett's is the "error" of the method. The relation between the error and axial length, ametropia, and keratometry was explored by linear regression analysis. RESULTS: Methods using axial length had the lowest mean (+0.5 to +2.6%) and standard deviation (0.6 to 1.2%) of errors. Of methods using keratometry and ametropia only, the lowest mean (-1.4% to +4.4%) and standard deviation (2.9 to 4.3%) of errors was found for a new method described in this paper, and that used by the Heidelberg retina tomograph (HRT). The highest mean error (+2.2 to +7.1%) was found for Littmann's method. Littmann's correction was larger than the HRT's by 3.5 to 3.7%. The mean difference between the new and HRT methods and the "abbreviated axial length" method of Bennett is -1.3 to +2.0%. The error of the "keratometry and ametropia" methods is related to axial length. CONCLUSIONS: Methods using axial length are most accurate. The abbreviated axial length method of Bennett differs little from more detailed calculations and is appreciably more accurate than methods using keratometry and ametropia alone. If axial length is unknown, the new and the HRT methods give results closest to the abbreviated axial length method.

Aged↗

Automated static perimetry in myopes with peripapillary crescents--Part II.

Central visual fields were investigated by automated static perimetry, using programs 30-2 and 30-1 of the Humphrey Field Analyzer (HFA), in a group of healthy myopic individuals with peripapillary crescents and tigroid fundus changes only. Results were compared with 'non-myopic' and 'myopic subjects without crescents' control groups. The sample comprised 122 young, healthy volunteers between the ages of 18.5 and 35.4 years, free from any ocular or systemic disease, with refractive errors ranging from +4.00 to -25.75 D. Linear regression results are presented and may be useful in predicting the global indices mean deviation (MD) and mean sensitivity (MS), given either the axial length or ocular refraction, for medium and high myopes. Analysis of the HFA printouts revealed significantly depressed locations in all subject groups. However, locations identified at the 2, 1 and 0.5% probability levels were observed more frequently and more commonly in the myopes with peripapillary crescents than in the control groups. In this non-glaucomatous sample, four myopes had a borderline glaucoma hemifield test and two fell outside normal limits of this test. The superior hemifield, particularly the upper temporal quadrant, appeared to be most affected. Enlargement of the blind spot occurred in some subjects. Several possible explanations are suggested for the visual field sensitivity reduction in myopia.

Adolescent↗

Automated static perimetry in myopes with peripapillary crescents--Part I.

Central visual fields were investigated by automated static perimetry in a group of healthy myopic individuals with peripapillary crescents and tigroid fundus changes only. Results were compared with 'emmetropic' and 'myopic subjects without crescents' control groups. The sample comprised 122 young, healthy volunteers between the ages of 18.5 and 35.4 years, free from any ocular or systemic disease, with refractive errors ranging from +4.00 D to -25.75 D. Central visual fields were examined using programs 30-2 and 30-1 of the Humphrey Field Analyzer (HFA), which in combination yield a test point resolution of 4.2 degrees within the central 30 degrees. Visual field analysis showed a decline in the differential light sensitivity in myopes with peripapillary changes only, compared with the control groups. These field changes became more pronounced as the degree of myopia, axial length and area of the peripapillary crescent increased. Results suggest that the sensitivity decline of the central field occurs in subjects with axial lengths above 26 mm and more than 5 D of myopia. Knowledge of the likely field defects encountered in myopia will assist practitioners to distinguish between physiological and pathological fields in myopes.

Adolescent↗

Improvements on Littmann's method of determining the size of retinal features by fundus photography.

Littmann's formula relating the size of a retinal feature to its measured image size on a telecentric fundus camera film is widely used. It requires only the corneal radius, ametropia, and Littmann's factor q obtained from nomograms or tables. These procedures are here computerized for practitioners' convenience. Basic optical principles are discussed, showing q to be a constant fraction of the theoretical ocular dimension k', the distance from the eye's second principal point to the retina. If the eye's axial length is known, three new methods of determining q become available: (a) simply reducing the axial length by a constant 1.82 mm; (b) constructing a personalized schematic eye, given additional data; (c) ray tracing through this eye to extend calculations to peripheral retinal areas. Results of all these evaluations for 12 subjects of known ocular dimensions are presented for comparison. Method (a), the simplest, is arguably the most reliable. It shows good agreement with Littmann's supplementary procedure when the eye's axial length is known.

Fundus Oculi↗

Repeatability, reproducibility and intersession variability of the Allergan Humphrey ultrasonic biometer.

We evaluated repeatability and reproducibility of the Allergan Humphrey model 820 ultrasonic biometer. Sixty eyes (30 subjects) free from ophthalmological abnormality were examined on two separate occasions by two experimenters, one experienced and one inexperienced. The 95% confidence limits for repeatability lie between +0.12/-0.13 mm and reproducibility between +0.15/-0.14 mm for AC depth, between +0.11/-0.13 mm and +0.12/-0.16 mm for lens thickness, between +0.17/-0.19 mm and +0.19/-0.18 mm for right axial length and between +0.26/-0.40 mm and +0.22/-0.25 mm for left axial length. The 40% gain used to measure left axial lengths produced poor retinal echospikes, which may account for reduced accuracy compared to the right eyes using 60% gain. Ten subjects (20 eyes) returned for 3 further visits and the variability over 5 sessions was examined using a two-factor ANOVA with repeated measures on one factor. There were no significant experimenter or session effects and no interaction effect. This biometer gives clinically repeatable and reproducible results and is convenient to use.

Anterior Chamber↗

Construction of a model eye and its applications.

Construction details are given of a model eye, based on the Bennett and Rabbetts schematic eye. It incorporates a cornea, lens, and spherical fundus. Distilled water filled the anterior and vitreous chambers. By means of a micrometer screw, the vitreous chamber depth can be precisely varied to produce axial ametropia from +11 to -17 D. Readings taken over the greater part of this range with a Topcon Autorefractor RM-A6500 were found to be repeatable and reproducible within +/- 0.25 D. The model eye was used to investigate the relationship between the actual size of a fundus feature and its photographic image in two different fundus cameras. With a Zeiss Oberkochen camera of telecentric design the magnification was found to remain constant whatever the degree of axial ametropia, whereas with a Carl Zeiss Jena camera the magnification varied linearly with ametropia. A technique developed by Littmann for determining the actual size of a retinal feature when using a fundus camera of telecentric design is discussed briefly.

Eye↗