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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 55 records · Page 3Linked to original sources
PubMed2000

Converting visual acuity to utilities.

BACKGROUND: Utility theory can be used to quantify dysfunction associated with various diseases and thus can represent a "hard" measure of quality of life. By determining utility values, one can compare the quality of life of patients with ocular disease to that of patients with non-ophthalmic problems. We performed a study to determine whether utility values from patients with ocular disease are associated with clinical variables, including visual acuity in the better-seeing eye, and to develop a mathematical method for converting visual acuity to utility value, if there is an association between the two. METHODS: Cross-sectional study. A total of 239 patients from a tertiary care retinal practice with various ocular conditions, including macular degeneration, cataract, glaucoma and diabetic retinopathy, were interviewed under standardized conditions to determine their utility values by the time trade-off technique. Visual acuity, duration of visual loss and number of concomitant conditions were also determined. Multiple linear regression was performed to determine which variables were associated with utility values. RESULTS: The mean acuity in the better-seeing eye was 0.479 (near 20/40 vision). The mean utility value was 0.72. Accordingly, the average patient in our series was willing to trade 2.8 of every 10 remaining years of life to obtain perfect vision in both eyes. Utility value was significantly associated with visual acuity in the better-seeing eye (F = 69.1, p < 0.001). Other variables were not significantly associated with utility value. The association with duration of visual loss approached statistical significance (p = 0.075). Utility values (U) for patients with ocular disease can be derived from the following formula: U = (0.374)(visual acuity in better-seeing eye) + 0.514. INTERPRETATION: Utility values from patients with ocular disease were strongly associated with visual acuity and could be estimated mathematically.

Aged↗
PubMed2000

Characteristics of patients presenting with central retinal artery occlusion with and without giant cell arteritis.

BACKGROUND: In patients with concurrent central retinal artery occlusion (CRAO) and giant cell arteritis (GCA), prompt recognition and early treatment are crucial to prevent further visual loss in the contralateral eye. The objective of this study was to describe a series of patients with CRAO resulting from GCA and to compare them with patients with isolated CRAO. METHODS: The patient database for a retina service in Philadelphia was searched to identify patients admitted between 1983 and 1993 with a diagnosis of biopsyproven GCA and CRAO. For every patient with CRAO caused by GCA, the next patient admitted for management of acute isolated CRAO was identified; these latter patients constituted the control group. The visual acuity and baseline characteristics of the two groups were compared. RESULTS: Eleven patients with acute CRAO and GCA were admitted during the study period. In both the case and control groups seven patients (64%) were women and nine patients (82%) were white. Six subjects (54%) in the case group and seven (64%) in the control group had a history of hypertension; the values for diabetes mellitus were two (18%) and zero respectively. Four patients (36%) with CRAO and GCA were cigarette smokers, compared with eight patients (73%) with CRAO alone. None of these differences were statistically significant. Patients with CRAO related to GCA were more likely than those with isolated CRAO to have counting fingers or better vision at presentation (odds ratio 2.22 [95% confidence interval 0.37 to 13.2]), but this trend was not statistically significant. INTERPRETATION: Patients who presented with CRAO related to GCA were more than twice as likely as those with CRAO alone to have counting fingers or better visual acuity at the time of presentation. However, owing to the small sample, the power of this study to detect a true difference between the two groups was limited.

Adult↗
PubMed2000

Incremental cost effectiveness of laser photocoagulation for subfoveal choroidal neovascularization.

OBJECTIVE: To perform a patient preference-based, incremental cost-effectiveness analysis for laser treatment of subfoveal choroidal neovascularization. DESIGN: Computer-based econometric modeling. METHODS: The cost effectiveness of laser photocoagulation therapy was compared with the natural course of subfoveal choroidal neovascularization. The model applied long-term visual data from previous clinical trials, utility analysis (which reflects patient perceptions of quality of life associated with a health state), decision analysis with Markov modeling, and the economic principles of present value analysis with discounting to account for the time value of money. DATABASE: Data from patients eligible for treatment of subfoveal choroidal neovascularization obtained by researchers in the Macular Photocoagulation Study were used for the analysis. INTERVENTION: Modeled laser therapy for subfoveal choroidal neovasacularization in patients with age-related macular degeneration. MAIN OUTCOME MEASURE: Cost per quality-adjusted life-year ($/QALY gained) associated with laser therapy. RESULTS: Laser photocoagulation therapy for subfoveal choroidal neovascularization, as compared with no treatment, resulted in a mean gain of 0.257 QALYs per treated patient. Using a yearly discount rate of 3% to account for the time value of money and inflation, the resultant $/QALY gained was $5629. Sensitivity analysis used in the cost-effectiveness analysis resulted in a $/QALY gained of $4974 with no gained discount rate and $11,633 with a yearly discount rate of 10%. CONCLUSIONS: The incremental expense of laser therapy for the treatment of subfoveal choroidal neovascularization appears to be highly cost effective. The result, which takes into account patient preference-based utility data, compares quite favorably with other interventional therapies across different medical specialties.

Aged↗
PubMed2000

Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis.

OBJECTIVE: To compare visual outcomes between cases of acute postoperative endophthalmitis that did or did not receive intravitreal steroids. DESIGN: Retrospective nonrandomized comparative trial. PARTICIPANTS: Fifty-seven patients with postoperative endophthalmitis. INTERVENTION: Thirty-one patients with postoperative endophthalmitis resulting from cataract extraction received both intravitreal antibiotics and steroids, whereas the remaining 26 received only intravitreal antibiotics. MAIN OUTCOME MEASURES: Improvement in visual acuity. RESULTS: Multivariate logistic regression was used to analyze the variables that potentially influence a three-line visual acuity improvement. The mean baseline visual acuities of both groups were comparable. The use of intravitreal steroids reduced the probability of developing a three-line improvement in visual acuity (odds ratio [OR] = 0.287; 95% confidence interval [CI] [0.072-0.852]). On the basis of logistic regression analysis using our multivariate model, gender, baseline visual acuity, and pars plana vitrectomy were not significantly associated with visual outcome differences between the two groups. CONCLUSIONS: Patients who received intravitreal steroids had a significantly reduced likelihood of obtaining a three-line improvement in visual acuity. At a minimum our study provides no support for their use and, therefore, steroids may not be efficacious for acute endophthalmitis related to cataract extraction.

Acute Disease↗
PubMed2000

The use of in situ haemoglobin-free perfused liver in metabolic-control analysis.

In this study the network of ATP-consuming and -producing reactions, interacting via the cytosolic ATP/ADP+P(i) system, was studied for the first time in an intact organ, the isolated perfused rat liver, using top-down metabolic-control analysis. Flux control in the metabolically resting state (only oxidative phosphorylation and ion pumps active) was only in the ATP-consumers, whereas in the metabolically active state (biosyntheses and ion-pumping ATPases active) most control over oxidative phosphorylation was in itself and some control was in ion-pumping ATPases. All ATP-consumers had high control over themselves, and ion-pumping ATPases had high negative control over the other ATP-consuming branches. Oxidative phosphorylation had high positive control over ATP-consuming reactions except for ion-pumping ATPases. It is concluded that in the active state ATP-consumers compete for cytosolic ATP, but as the ion-pumping ATPases and oxidative phosphorylation are less sensitive towards the cytosolic ATP, other ATP-consumers have low control over these pathways.

Adenosine Diphosphate↗
PubMed2000

Nitric oxide as a competitive inhibitor of oxygen consumption in the mitochondrial respiratory chain.

Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by various means. The author and others have shown that low (nanomolar) concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase in competition with oxygen, in isolated cytochrome oxidase, mitochondria, nerve terminals, cultured cells and tissues. Primary astrocytes and a macrophage cell line, activated by cytokines and endotoxin to express the inducible isoform of NO synthase, strongly and reversibly inhibited their own respiration and that of co-incubated cells by this means. Primary aortic endothelial cells transiently inhibited their own respiration when NO production was acutely stimulated with bradykinin or ATP, and basal NO release increased the apparent Km for oxygen of respiration in these cells. Thus the NO inhibition of cytochrome oxidase may be involved in the physiological and/or pathological regulation of respiration rate and its affinity for oxygen.

Animals↗
PubMed2000

Modelling haemopoietic stem cell division by analysis of mutant red cells.

Data describing the number of human red cells mutated at the glycophorin A locus, measured flow cytometrically, are reported for 752 adults and 49 neonates. The variance increases with age more rapidly than the approximately linear increase in mean. It is postulated that this discrepancy is explained by the known property of asymmetric stem cell division, so that the division of a single mutant stem cell may result in zero, one or two progeny stem cells. A mathematical analysis allows description of this process with three parameters: stem cell number, mean division rate and mutation rate per division. The values of these parameters can not be deduced from the data presented here. However, estimates of either stem cell number or mutation rate from other sources enable deduction of the two other parameters. The mean number of divisions per stem cell per lifetime was estimated to be about 70. This analysis therefore implies that the rate at which blood cell telomeres shorten with age acts as a direct measure of stem cell turnover. Furthermore, it is argued that this low figure implies that mutations occurring during early life, including organogenesis, are relatively important in initiating stem cell-derived malignancy. Finally, the number of human stem cell divisions per lifetime is similar to shorter-lived mammals, suggesting this number is important in the ageing process.

Adult↗
PubMed2000

Nitric-oxide-induced necrosis and apoptosis in PC12 cells mediated by mitochondria.

Nitric oxide (NO) can trigger either necrotic or apoptotic cell death. We have used PC12 cells to investigate the extent to which NO-induced cell death is mediated by mitochondria. Addition of NO donors, 1 mM S-nitroso-N-acetyl-DL-penicillamine (SNAP) or 1 mM diethylenetriamine-NO adduct (NOC-18), to PC12 cells resulted in a steady-state level of 1-3 microM: NO, rapid and almost complete inhibition of cellular respiration (within 1 min), and a rapid decrease in mitochondrial membrane potential within the cells. A 24-h incubation of PC12 cells with NO donors (SNAP or NOC-18) or specific inhibitors of mitochondrial respiration (myxothiazol, rotenone, or azide), in the absence of glucose, caused total ATP depletion and resulted in 80-100% necrosis. The presence of glucose almost completely prevented the decrease in ATP level and the increase in necrosis induced by the NO donors or mitochondrial inhibitors, suggesting that the NO-induced necrosis in the absence of glucose was due to the inhibition of mitochondrial respiration and subsequent ATP depletion. However, in the presence of glucose, NO donors and mitochondrial inhibitors induced apoptosis of PC12 cells as determined by nuclear morphology. The presence of apoptotic cells was prevented completely by benzyloxycarbonyl-Val-Ala-fluoromethyl ketone (a nonspecific caspase inhibitor), indicating that apoptosis was mediated by caspase activation. Indeed, both NO donors and mitochondrial inhibitors in PC12 cells caused the activation of caspase-3- and caspase-3-processing-like proteases. Caspase-1 activity was not activated. Cyclosporin A (an inhibitor of the mitochondrial permeability transition pore) decreased the activity of caspase-3- and caspase-3-processing-like proteases after treatment with NO donors, but was not effective in the case of the mitochondrial inhibitors. The activation of caspases was accompanied by the release of cytochrome c from mitochondria into the cytosol, which was partially prevented by cyclosporin A in the case of NO donors. These results indicate that NO donors (SNAP or NOC-18) may trigger apoptosis in PC12 cells partially mediated by opening the mitochondrial permeability transition pores, release of cytochrome c, and subsequent caspase activation. NO-induced apoptosis is blocked completely in the absence of glucose, probably due to the lack of ATP. Our findings suggest that mitochondria may be involved in both types of cell death induced by NO donors: necrosis by respiratory inhibition and apoptosis by opening the permeability transition pore. Further, our results indicate that the mode of cell death (necrosis versus apoptosis) induced by either NO or mitochondrial inhibitors depends critically on the glycolytic capacity of the cell.

Adenosine Triphosphate↗
PubMed2000

Incremental cost-effectiveness of laser therapy for choroidal neovascularization associated with histoplasmosis.

PURPOSE: Laser photocoagulation has been shown in a large clinical trial to be efficacious in reducing the degree of vision loss occurring secondary to choroidal neovascularization (CNV) associated with ocular histoplasmosis. Nevertheless, data are lacking concerning the impact of the therapy on quality of life and its value to stakeholders in health care. Recently, information concerning the utility value of visual states has become available. Accordingly, the authors undertook to ascertain the cost-effectiveness of laser photocoagulation for the treatment of extrafoveal CNV occurring in eyes with ocular histoplasmosis. METHODS: Design--A computer simulation, econometric model is presented to evaluate the incremental cost-effectiveness of laser photocoagulation therapy, as compared with the natural course of the disease, for the treatment of patients with extrafoveal CNV associated with ocular histoplasmosis. The model applies long-term visual data from previous clinical trials, utility analysis (which reflects patient perceptions of quality of life), decision analysis with Markov modeling, and present value analysis with discounting to account for the time value of money. Outcome measure--Cost per quality-adjusted life-year gained from treatment. RESULTS: Laser photocoagulation therapy for extrafoveal CNV associated with ocular histoplasmosis costs $4167 1999 US dollars (at a 3% discount rate) for each quality-adjusted life-year gained from treatment. Sensitivity analysis shows that changing the discount rate substantially alters the cost-effectiveness, with a value of $1339 at a 0% discount rate and $56,250 at a 10% discount rate. CONCLUSIONS: Compared with therapeutic modalities for other disease entities, laser therapy for the treatment of extrafoveal CNV associated with ocular histoplasmosis appears to be a cost-effective treatment from the patient preference-based point of view.

Adult↗
PubMed2000

The cost-effectiveness of grid laser photocoagulation for the treatment of diabetic macular edema: results of a patient-based cost-utility analysis.

Grid laser therapy has been demonstrated to be of benefit for the treatment of diabetic macular edema. The purpose of the present study was to determine the cost-effectiveness of grid laser therapy for the treatment of diabetic macular edema. The analysis was performed from the perspective of a third-party insurer. Decision analyses and cost-effectiveness analyses were performed by incorporating the data from the Early Treatment Diabetic Retinopathy Study, expected longevity data, and patient-based utilities. Various sensitivity analyses were performed to determine the robustness of the models. Laser treatment conferred an overall improvement in quality-of-life adjusted years of approximately 3 months over the duration of disease for a hypothetical patient. The unadjusted cost per quality-of-life adjusted year (QALY) was US$3,101. Net present value analysis demonstrated that the cost per QALY could increase to $3,655, assuming a 5% discount rate. Overall, grid laser photocoagulation for diabetic macular edema is a very cost-effective treatment based on the results of this cost-utility analysis.

Adult↗
PubMed2000

The antiphospholipid antibody syndrome.

Antiphospholipid syndrome includes elevation of either the lupus anticoagulant titer or the anticardiolipin antibody titer on two occasions, separated by 6 weeks in a patient with an episode of thrombosis. The eye is involved frequently in patients with antiphospholipid syndrome. Patients with retinal vascular disease and none of the usual risk factors for retinal vascular disease should be considered at risk for expressing this syndrome.

Antibodies, Anticardiolipin↗
PubMed2000

Systemic disorders associated with retinal vascular occlusion.

Occlusions of the retinal arterial and venous circulations are common causes of severe visual decline and can affect all age groups. Acute retinal arterial obstruction is often associated with critical cerebrovascular and cardiovascular disease that may require systemic treatment. Retinal venous obstruction may be the presentation of significant systemic hypertension, diabetes mellitus, and a greater risk for cardiovascular morbidity. Additional metabolic and hematologic abnormalities have been identified in patients with retinal occlusive disease. The authors review recent advances in the study of systemic conditions associated with retinal vascular occlusions and offer guidelines for appropriate medical evaluation of patients with retinal occlusive disease.

Blood Coagulation↗
PubMed2000

Analysis of costs.

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Choroid Neoplasms↗
PubMed2000

Health care in the 21st century: evidence-based medicine, patient preference-based quality, and cost effectiveness.

The combination of evidence-based medicine, patient-based preferences using utility analysis, and econometric modeling yields a model to evaluate the incremental cost effectiveness of health care interventions. This methodology allows a comparison of the cost effectiveness of virtually all health care interventions and incorporates the patient voice to provide an information system that can improve the quality of health care and simultaneously reduce costs. It has been estimated that such an information system could save more than $90 billion per year of the annual $1.3 trillion health care bill in the United States.

Cost-Benefit Analysis↗
PubMed1999

Spatial gradients of cellular phospho-proteins.

If a protein is rapidly phosphorylated and dephosphorylated at separate cellular locations and protein diffusion is slow, then a spatial gradient of the phosphorylated form of the protein may develop within the cell. We have estimated the potential size of such gradients using measured values of protein diffusion coefficients and protein kinase and phosphatase activities. We analysed two different cellular geometries: (1) where the kinases is located on the plasma membrane of a spherical cell and the phospatase is distributed homogenously in the cytoplasm and (2) where the kinase is located on one planar membrane and the phosphatase on a second parallel planar membrane. The estimated gradients of phospho-proteins were potentially very large, which has important implications for cellular signalling.

Biological Transport↗