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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 91 records · Page 5Linked to original sources
PubMed1998

Patient perceptions of quality-of-life associated with bilateral visual loss.

PURPOSE: To ascertain whether patients with unilateral visual loss to a specific level are able to approximate the degree of impairment of quality-of-life experienced by patients with bilateral visual loss to the same level. METHODS: One hundred thirty-three study group patients with (1) visual loss to 20/40 or worse in at least one eye, and (2) a marked difference between the visual acuities in their two eyes, were polled using the time tradeoff method of utility value measurement. All patients were asked to assume that the visual acuity in both of their eyes was as poor as the visual acuity in their worst seeing eye. These utility values were then compared to those obtained from a control group of 173 patients with known utility values who had similar bilateral visual loss. Both the study and control groups were stratified into 4 levels of visual loss (20/40 to 20/50, 20/60 to 20/100, 20/200 to 20/400, and counting fingers to light perception). RESULTS: Mean utility values for the study group ranged from 0.47 to 0.71. Patients with unilateral visual loss, given the assumption of bilateral visual loss to the same degree, routinely demonstrated no significant difference in utility preferences as compared to patients with true bilateral visual loss to the same level. CONCLUSIONS: Patients with unilateral visual loss can very accurately estimate the degree of impairment of quality-of-life that would result if visual loss to a similar degree occurred in the remaining eye with better vision.

Activities of Daily Living↗
PubMed1998

Nitric oxide causes glutamate release from brain synaptosomes.

We determined the ability of pathological levels of nitric oxide (NO) to cause glutamate release from isolated rat brain nerve terminals using a fluorometric assay. It was found that NO (0.7 and 2 microM) produced (4 and 10 nmol/mg of synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after 1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+-independent glutamate release. Preincubation of synaptosomes with 5 microM 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+-independent glutamate release produced by NO was greater in a low-oxygen medium. NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration with a similar order of potency with respect to their ability to cause glutamate release. Because NO has been shown previously to inhibit reversibly cytochrome oxidase in competition with oxygen, our findings in this study suggest that NO (and cyanide) causes glutamate release following inhibition of mitochondrial respiration at the level of cytochrome oxidase. Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicty may contribute to neuronal death in neurological diseases.

4-Aminopyridine↗
PubMed1998

Accuracy of visible retinal emboli for the detection of cardioembolic lesions requiring anticoagulation or cardiac surgery. Retinal Emboli of Cardiac Origin Study Group.

AIM: To determine the accuracy of visible retinal emboli as a diagnostic "test" for the likelihood of receiving anticoagulation or cardiac surgery based on the results of transthoracic echocardiography, in the setting of acute retinal arterial occlusion. METHODS: A multicentre retrospective diagnostic study at Kingston Eye Centre, Queen's University, Kingston, Ontario; Wills Eye Hospital, Philadelphia; Ottawa Eye Institute, Ottawa, Ontario; and the Halifax Infirmary, Halifax, Nova Scotia of 104 patients with both embolic and nonembolic acute retinal arterial obstruction who underwent transthoracic echocardiography was performed, to determine the accuracy of visible retinal emboli as a diagnostic "test" for anticoagulation or cardiac surgery. Anticoagulation or surgical intervention on the basis of abnormalities was detected solely through the technology of transthoracic echocardiography. RESULTS: 41 patients had visible retinal emboli (calcific, cholesterol, or fibrin). The remaining 63 had no evidence of embolic disease. The sensitivity of emboli for the likelihood of a patient receiving anticoagulation or cardiac surgery was 50%. The specificity, positive predictive value, and negative predictive value were 62%, 15%, and 90%, respectively. The likelihood ratio (LR = 1.31) obtained given the presence of a visible retinal embolus was neither clinically nor statistically significant (LR+ve = 1.31; 95% CI (0.91, 3.16)). This likelihood ratio, when applied to a patient with a pretest probability of 50%, results in a post-test probability of 56.7%. CONCLUSIONS: These results demonstrate that the presence of a visible retinal embolus should not be the sole determinant of whether to order transthoracic echocardiography, as the likelihood ratio for a patient receiving anticoagulation or cardiac surgery, given the presence of a visible retinal embolus was only 1.31.

Anticoagulants↗
PubMed1998

In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics.

PURPOSE: To image peripheral blood leukocyte traffic in the normal retinal and choroidal vasculature and to quantify the differences in the circulation dynamics between normal and concanavalin A (ConA)-activated leukocytes. METHODS: Normal or ConA-activated splenocytes were fluorescently labeled in vitro with 6-carboxyfluorescein diacetate (CFDA) and reinfused in vivo where they were tracked in the retinal and choroidal circulations of syngeneic rats by means of a scanning laser ophthalmoscope (SLO). Simultaneous digital and video images were captured for as long as 30 minutes, and the initial 15 seconds of image sequences and leukocyte dynamics were analyzed from digitized images by recording the velocity of trafficking cells and the number of stationary cells that accumulated with time, using a customized software package. RESULTS: Mean velocity (+/-SD) was 29.8 +/- 15.3 mm/sec in the retinal arteries, 14.7 +/- 7.2 mm/sec in the retinal veins, and 3.0 +/- 3.6 mm/sec in the retinal capillaries. Mean velocity in the choroidal vessels was 6.1 +/- 6.0 mm/sec. No significant difference in leukocyte velocity was found between activated and normal leukocytes in any of the vessel systems. However, activated leukocytes were observed to accumulate more within the choroidal vasculature (P < 0.001) and the retinal capillaries (P < 0.001) than in control animals, but not in larger retinal vessels. CONCLUSIONS: A technique to measure the kinetics of circulating leukocytes in vivo has been developed. Although leukocyte activation itself is insufficient to cause slowing of leukocyte velocity, the data indicate that leukocyte adherence to endothelium can be induced in the absence of local or systemic activating stimuli.

Animals↗
PubMed1997

Activated human neutrophils rapidly break down nitric oxide.

Isolated human neutrophils produced no detectable (< 10 nM) nitric oxide (NO) before or after activation with phorbol 12-myristate 13-acetate (PMA) or a chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Physiological levels of NO (1 microM) added before or after neutrophil activation had no effect on their respiratory burst oxygen consumption. Neutrophils activated with PMA caused very rapid breakdown of exogenously added NO. NO breakdown rates recorded at 250 nM NO were 0.09 +/- 0.02 and 3.77 +/- 0.23 nmol NO/min/10(6) cells (n = 3) before and after activation respectively and addition of copper-zinc superoxide dismutase during activation significantly decreased this rate (1.06 +/- 0.09 nmol NO/min/10(6) cells (n = 3)), suggesting that superoxide (O2-) production was mainly responsible for the NO breakdown. These results suggest that activation of human neutrophils in vivo will dramatically decrease surrounding NO levels, potentially causing vasoconstriction, platelet aggregation and adhesion and peroxynitrite (ONOO-) formation.

Humans↗
PubMed1997

Radiation therapy for macular degeneration: technical considerations and preliminary results.

PURPOSE: This study was undertaken to assess the toxicity and possible benefits from the administration of low-dose external-beam irradiation for Age-Related Macular Degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neo-vasculature, resulting in reabsorption of fluid and blood thus reducing the risk for further leakage or bleeding, as well as subretinal fibrosis. Clinically, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet type of ARMD with the possibility for some visual improvement. METHODS AND MATERIALS: Allegheny University Hospitals, Hahnemann, Department of Radiation Oncology, treated 278 patients prospectively beginning in January 1995 with low-dose irradiation for wet-type macular degeneration. Two hundred forty-nine patients were treated with a total dose of 14.40 Gy in eight fractions of 1.80 Gy over 10-13 elapsed days, and 27 patients with 20 Gy at 2 Gy per fraction over 12-15 days. The first two patients were treated to a total dose of 10.00 Gy in five fractions of 2.00 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. A percentage (36.7%) of the patients had previously received laser treatments in the study eye, 21.9% once, 5% twice, 9.7% three or more. Subjective visual acuity and toxicity data was collected on all patients. RESULTS: At 2-3 weeks after treatment 195 patients (70%) retained their visual acuity without change, 68 patients (24.5%) stated they had improved vision, and 15 patients (4.8%) stated their vision continued to decrease. Two to 3 months after treatment, 183 patients (65.8%) had no change in their vision, 75 patients (27%) had an improvement in their vision, and 20 patients (7.2%) had a decrease in visual acuity. Transient acute reactions occurred in 14 of the 278 patients treated. CONCLUSION: Our observations in this group of 278 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age related wet type macular degeneration.

Adult↗
PubMed1997

Quantification of information transfer via cellular signal transduction pathways.

A conceptual framework is developed for the quantitative analysis of signal transfer through cellular signal transduction pathways and networks. This approach is referred to as signal transfer analysis and is based on formalisms that were first developed for the analysis of metabolic networks. Signal transduction is quantified as the sensitivity, known as the response coefficient of a target (e.g. an ion channel or transcription factor) to a signal (e.g. a hormone, growth factor or neurotransmitter). This response coefficient is defined in terms of the fractional change in the activated target brought about by a small fractional change in the signal. Quantifying the signal transduction in this way makes it possible to prove that for an idealized signaling cascade without feedback loops, the total response equals the product of all the local response coefficients, one for each level of the cascade. We show under which conditions merely having more levels in a cascade can boost the sensitivity of a target to a signal. If a signal propagates to a target through two different routes, these routes contribute independently to the total response, provided there is no feedback from the target. This independence makes the behavior of signaling cascades different from that of metabolic pathways, where different branches are connected through Kirchhoffs law. The relations between the total response and the local kinetics at each level are given for a number of network structures, such as branched signaling pathways and pathways with feedback. The formalism introduced here may provide a general approach to quantify cellular information transfer.

Cell Physiological Phenomena↗
PubMed1997

Peripapillary staphyloma.

PURPOSE: To report a rare case of peripapillary staphyloma. METHOD: Case report. A 5-month-old infant was examined for esotropia associated with a retinal and optic nerve abnormality of the left eye. RESULTS: Detailed clinical examination along with diagnostic ultrasonography and electroretinography established a diagnosis of a peripapillary staphyloma of the left eye measuring 9.77 mm in depth. The patient's right eye was entirely normal, and she showed no systemic abnormalities. CONCLUSION: Although extremely rare, the peripapillary staphyloma may cause severe visual impairment of the affected eye in an otherwise healthy individual unassociated with systemic abnormalities.

Electroretinography↗
PubMed1997

Surgical removal of subfoveal neovascularization in idiopathic juxtafoveolar retinal telangiectasis.

PURPOSE: To investigate the efficacy of the surgical removal of subfoveal choroidal neovascularization in patients with type 2A idiopathic juxtafoveolar retinal telangiectasis. METHODS: Two patients with bilateral acquired idiopathic juxtafoveolar retinal telangiectasis and a subfoveal choroidal neovascular membrane underwent surgical excision of the membrane using standard subretinal surgical techniques. RESULTS: In both cases, surgical removal of the neovascular membrane was complicated by an intimate adherence of the membrane with the overlying neurosensory retina in an area of retinochoroidal anastomosis. A retinal dehiscence occurred in both instances at the time of surgery. Postoperative visual outcome was poor. CONCLUSION: The retinochoroidal anastomoses often visualized in cases of subretinal neovascularization complicating bilateral acquired IJFRT could indicate that there is a fairly marked adherence of the neovascular membrane to the neurosensory retina. Attempts at surgical removal of subretinal membranes in this disease entity with current techniques may be contraindicated.

Choroid↗
PubMed1997

Cellular energy utilization and molecular origin of standard metabolic rate in mammals.

The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Adenosine Triphosphate↗
PubMed1997

Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia and delayed cerebral energy failure in the newborn piglet.

Studies of the brains of severely birth-asphyxiated infants using proton (1H) magnetic resonance spectroscopy (MRS) have shown changes indicating a rise in cerebral lactate (Lac) and a fall in N-acetylaspartate (Naa). The aim of this study was to test two hypotheses: 1) that these changes can be reproduced in the newborn piglet after transient reversed cerebral hypoxiaischemia, and their time course determined; and 2) that changes in Lac peak-area ratios are related to changes in phosphorylation potential as determined by phosphorus (31P) MRS. Eighteen piglets aged < 24 h were anesthetized and ventilated. Twelve underwent temporary occlusion of the carotid arteries and hypoxemia, and six served as sham-operated controls. 1H and 31P spectra were acquired alternately, both during the insult and for the next 48 h, using a 7-tesla spectrometer. During hypoxiaischemia, the median Lac/total creatine (Cr) peak-area ratio rose from a baseline of 0.14 (interquartile range 0.07-0.27), to a maximum of 4.34 (3.33-7.45). After resuscitation, Lac/Cr fell to 0.75 (0.45-1.64) by 2 h, and then increased again to 2.43 (1.13-3.08) by 48 h. At all stages after resuscitation Lac/Cr remained significantly above baseline and control values. Naa/Cr was significantly reduced below baseline and control values by 48 h after resuscitation. The increases in the Lac peak-area ratios were concomitant with the falls in the [phosphocreatine (PCr)*]/ [inorganic phosphate (Pi)] ratio, during both acute hypoxiaischemia and delayed energy failure. The maximum Lac/Naa during delayed energy failure correlated strongly with the minimum [nucleotide triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] (r = -0.94, p < 0.0001). We conclude that both hypotheses have been confirmed.

Animals↗
PubMed1997

Transthoracic echocardiography in young patients with acute retinal arterial obstruction. RECO Study Group. Retinal Emboli of Cardiac Origin Group.

OBJECTIVE: To report the transthoracic echocardiographic findings in young patients presenting with acute retinal arterial obstruction, given their clinical risk status for cardioembolic disease. DESIGN: Case series. SETTING: Four North American tertiary hospital centres. PATIENTS: Eleven patients less than 45 years of age presenting with acute retinal arterial obstruction who underwent transthoracic echocardiography. OUTCOME MEASURES: Anticoagulation therapy or cardiac surgery. RESULTS: Echocardiography showed abnormalities in five patients (45%). Five of the 11 patients were at high risk for cardioembolic disease on the basis of a history of risk factors or the presence of a cardiac murmur on presentation, or both. Three (60%) of the five had abnormal findings on echocardiography; all three required anticoagulation therapy or cardiac surgery. Of the six patients at low risk two (33%) had abnormal echocardiograms; neither required anticoagulation therapy or surgical intervention. CONCLUSIONS: All the patients who required anticoagulation therapy or cardiac surgery based on the findings on transthoracic echocardiography were deemed to be at high risk for cardioembolic disease. This emphasizes the importance of clinical risk stratification in the systemic evaluation of young patients presenting with acute retinal arterial obstruction.

Acute Disease↗