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Biomedical subjects

G C Brown

Publications and source records attributed to G C Brown.

At least 19 recordsLinked to original sources

Sudden retinal manifestations of intranasal cocaine and methamphetamine abuse.

We examined two patients who had sudden decrease in vision after intranasal cocaine or methamphetamine abuse. A 38-year-old woman with a history of systemic arterial hypertension developed a central retinal artery occlusion four hours after intranasal use of cocaine. A 26-year-old woman had blurred vision and intraretinal hemorrhages shortly after using methamphetamine nasally. The adrenomimetic response and sudden increase in blood pressure associated with the intranasal use of these drugs may have contributed to the retinal vascular manifestations observed in these patients.

Cocaine

Control of respiration and ATP synthesis in mammalian mitochondria and cells.

We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate

Reoperation following diabetic vitrectomy.

A review of 484 consecutive eyes that were undergoing an initial pars plana vitrectomy for the sequelae of proliferative diabetic retinopathy disclosed that 41 eyes (8.5%) required one or more additional vitrectomy operations. The primary causes for reoperation included rhegmatogenous retinal detachment in 18 (44%) of the 41 eyes, recurrent vitreous hemorrhage in 21 eyes (51%), and glaucoma in two eyes (5%). The visual prognosis was worse in the group with rhegmatogenous retinal detachment, with 10 (56%) of 18 eyes progressing to no light perception (P = .003). Severe preretinal and subretinal fibrous proliferation, as demonstrated histopathologically, accounted in large part for the poor result. The preretinal membrane formation appeared to occur secondary to a combination of diabetic extraretinal vascular growth and proliferative vitreoretinopathy. Among the total group of 41 eyes that required subsequent surgery, the retina eventually remained detached in 18 eyes (44%), and phthisis bulbi occurred in 13 eyes (32%). Rubeosis iridis developed in 17 (94%) of 18 eyes in which the retina remained detached.

Adult

Visual symptoms associated with choroidal neovascularization. Photopsias and the Charles Bonnet syndrome.

One hundred consecutive patients with macular choroidal neovascularization were studied in a cross-sectional fashion. Evidence of bilateral choroidal neovascularization was present in 31 patients. Among the 100 subjects, 59% related a history of seeing flickering or flashing lights (photopsias) in the affected eye or eyes. The colors varied, but in 59% of instances the lights were white. Twelve subjects experienced formed hallucinations (Charles Bonnet syndrome); in nine (75%) of these patients, the sequelae of choroidal neovascularization were bilateral. Symptoms that are commonly attributed to vitreoretinal tractional phenomena as well as neurologic and/or psychiatric disease are also frequently encountered in patients with macular degeneration associated with choroidal neovascularization.

Adult

Diode laser photocoagulation for retinopathy of prematurity. Preliminary results.

In a prospective, randomized clinical trial comparing transscleral cryotherapy with laser photocoagulation in the treatment of "threshold" stage 3+ retinopathy of prematurity, 32 infants were treated with diode laser photocoagulation in one eye. Twenty-eight infants have been followed up for at least 3 months, and seven have been followed up for at least 1 year. Twenty-five of 28 eyes treated with diode laser photocoagulation and followed up for at least 3 months have undergone regression. Of 24 fellow eyes treated with cryotherapy and followed up for at least 3 months, 20 have undergone regression. All seven eyes treated with diode laser photocoagulation and followed up for at least 1 year have undergone regression. Of seven fellow eyes treated with cryotherapy and followed up for at least 1 year, all have undergone regression. Our results suggest that diode laser photocoagulation is as effective as cryotherapy in the treatment of retinopathy of prematurity.

Cryosurgery

Color Doppler imaging of the ocular ischemic syndrome.

PURPOSE: This study describes hemodynamic characteristics of the ophthalmic, central retinal, and posterior ciliary arteries in 16 eyes of 11 patients with the ocular ischemic syndrome. Understanding the hemodynamic characteristics of the retrobulbar circulation may elucidate the natural history and pathophysiology of the ocular ischemic syndrome and perhaps form the basis for rational treatment of this condition. METHODS: Color Doppler imaging, a procedure that permits rapid noninvasive imaging of the ophthalmic, central retinal, and posterior ciliary arteries, was used to quantitate peak systolic blood flow velocities and vascular resistance (pulsatility index) within these vessels in study group eyes and in an age-matched control population. RESULTS: We demonstrated markedly reduced ocular ischemic syndrome central retinal and posterior ciliary artery peak systolic velocities compared with control group eyes. Central retinal and posterior ciliary artery vascular resistance (pulsatility index) was greater in ocular ischemic eyes versus control group eyes. Reversal of ophthalmic artery blood flow was detected in 12 of 16 ocular ischemic syndrome eyes. Study group eyes with poor vision had no detectable posterior ciliary arterial blood flow. CONCLUSION: Color Doppler imaging quantitates hemodynamic characteristics of the retrobulbar circulation in the ocular ischemic syndrome. There is markedly reduced peak systolic velocity and increased vascular resistance in ocular end arteries such as the central retinal and posterior ciliary arteries. Ophthalmic artery reversal of flow seems to represent collateral blood flow to lower resistance vascular beds. Posterior ciliary artery hypoperfusion may correlate with poor vision in the ocular ischemic syndrome.

Aged

Pseudophakic retinal detachments. Anatomic and visual results.

Retinal reattachment rates and visual results were analyzed in 227 consecutive primary pseudophakic rhegmatogenous retinal detachments. The overall anatomic reattachment rate was 90%, with no significant difference between the anterior chamber (AC) and posterior chamber intraocular lens groups. Visual results were significantly worse in the AC lens group (P less than 0.05). Negative prognostic indicators for reattachment included age greater than 65 years, poorer preoperative vision, larger extent of the retinal detachment, inability to identify a retinal break, longer duration of symptoms before presentation, and grades C or D proliferative vitreoretinopathy (P less than 0.05). In addition to the above factors, eyes with AC reaction, AC lenses, and macular detachment had a poorer visual prognosis.

Adult

The leaks and slips of bioenergetic membranes.

Bioenergetic membranes use proton gradients to transduce energy. However, when the proton gradient is large 1) there is a passive leak of protons (and other ions) across these membranes, and 2) some proton pumps may fail to pump protons (a phenomenon known as slip). Leaks and slips may be an unavoidable consequence of membrane structure and cause significant wastage of free energy, but they may also have functional roles beneficial to the organism.

Animals

Distribution of the posterior ciliary arteries revealed after vascular occlusions. A case report.

Recognized posterior ciliary artery occlusion combined with central retinal artery occlusion is relatively uncommon. Clinical and experimental evidence of combined occlusions appear to support a nasal and temporal distribution for the posterior ciliary arteries in most cases. A case involving a patient in whom the posterior ciliary arteries divided superiorly and inferiorly to supply the region of the macula is reported. Some of the more common variations in the distribution of the posterior ciliary arteries are discussed. Clinicians should be aware that the territorial divisions of the choroidal perfusion in the macula may be horizontally based.

Arterial Occlusive Diseases

Purtscher's retinopathy preceding acute pancreatitis.

A patient with a long history of alcohol abuse had diminished vision. The clinical and angiographic findings were consistent with Purtscher's retinopathy. Subsequently, the patient was hospitalized for acute pancreatitis. To our knowledge, this is the first reported case of pancreatic retinopathy preceding the systemic findings of acute pancreatitis.

Acute Disease

Total cell protein concentration as an evolutionary constraint on the metabolic control distribution in cells.

Cell protein occupies 15-35% of cell volume. This level is argued to be the maximum compatible with cell function. Because of this constraint, selection pressure during evolution is likely to have maximized pathway fluxes for minimum total protein level. Pathways optimized in this way are shown to have the following characteristics: (1) the "simple" flux control coefficients of all enzymes are equal, (2) the normal flux control coefficients depend on the relative kinetic constants of the enzymes, such that enzymes with low specific activity are present at relatively high levels and have high flux control, (3) the normal flux control coefficients are proportional to enzyme levels. A single rate limiting step located at the first step in a pathway is likely to be inefficient in terms of protein levels, and the major metabolic pathways are therefore expected to have control distributed throughout the pathway. This has important implications for metabolic control.

Animals

On the nature of the mitochondrial proton leak.

Respiring mitochondria have a significant passive permeability to protons; the mechanism of this proton leak is unknown. Several putative mechanisms were tested. Mitochondrial permeability to small sugars was unaffected by energization, suggesting that there is no significant dielectric breakdown at high membrane potential. Mitochondria are argued to have a proton permeability that is 6 to 8 orders of magnitude higher than the permeability to other cations, suggesting that the proton leak is probably not via a simple pore or membrane defect. 15-30% of the proton leak of freshly prepared mitochondria was extractable with bovine serum albumin and is probably due to fatty acids. Little if any of the proton leak appears to be due to cycling of ions other than protons, or to be associated with the functional activity of the proton pumps. The mitochondrial proton leak shares several properties with the proton permeability of pure phospholipid bilayers, suggesting that they share the same mechanism, although the leak through the bilayer in mitochondria may be modified by the presence of proteins.

Animals

Cytochrome oxidase content of rat brain during development.

The cytochrome oxidase concentration and content of rat brain during development was measured using a simple new assay for cytochrome a. The cytochrome oxidase concentration increased from 1.2 nmol/g wet wt. of brain at birth to about 5.5 nmol/g in the adult, most of the change occurring between 5 and 25 days after birth.

Animals

Prevalence and association of asteroid hyalosis with systemic diseases.

We performed a cross-sectional study of 12,205 patients, which identified 101 patients (0.83%) with asteroid hyalosis. These patients were examined for associated systemic and ocular conditions. Diabetes mellitus was found in 29 of the patients with asteroid hyalosis (29%), as compared to ten of 101 (10%) control subjects (P = .0007). An increased prevalence of systemic arterial hypertension (61 of 101 [60%] patients with asteroid hyalosis compared with 29 of 101 [29%] control subjects; P = .0001) and atherosclerotic vascular disease (30 of 101 [30%] patients with asteroid hyalosis compared with 13 of 101 [13%] control subjects; P = .006) was also discovered in the asteroid hyalosis group. Additionally, patients with asteroid hyalosis were found to be more hyperopic than control subjects (P = .009).

Adult

A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization.

We conducted a prospective study to determine the incidence of ocular neo-vascularization following acute central retinal artery obstruction. Only patients initially evaluated within 7 days of visual loss were eligible. Any patient with pre-existing ocular neovascularization or clinical evidence of the ocular ischemic syndrome noted at the initial evaluation was excluded. During the 18-month study, 33 consecutive patients were enrolled. Six patients subsequently developed neovascularization of the iris, an incidence of 18.2%. In these six patients, neovascularization of the iris appeared as early as 12 days to as late as 15 weeks following the artery obstructions. Five of the six patients (15.2% of the total) later developed neovascular glaucoma. Another patient in this series developed neovascularization of the optic disc without neovascularization of the iris, an incidence of 3.0%. Only two of the seven patients with ocular neovascularization had ipsilateral hemodynamically significant carotid artery disease as determined by noninvasive carotid artery testing. This study confirms results of previous retrospective studies that the incidence of ocular neovascularization after central retinal artery obstruction is higher than commonly thought. It also shows that, in the majority of cases, carotid artery disease is not responsible for the neovascularization seen after central retinal artery obstruction.

Acute Disease

Foveal avascular zone diameter and sickle cell disease.

Patients with sickle cell disease can have a distinct retinopathy in which the posterior pole shows abnormalities, including perifoveolar vascular abnormalities. The foveal avascular zone (FAZ) was examined using fluorescein angiography in patients with sickle cell disease and in healthy normal controls. The longest FAZ diameters of 38 patients (51 eyes) with sickle cell disease were compared with those of the 48 patients (60 eyes) in the control group. The average of the longest FAZ diameter in the patients with sickle cell disease was 1.00 mm compared with 0.61 mm for the controls. This difference was statistically significant (P less than .00001). Within the sickle cell group, there were no significant differences in the FAZ diameters with respect to degree of retinopathy, type of sickle hemoglobinopathy, or visual acuity. Thus, an enlarged FAZ diameter in patients with sickle cell disease is confirmed.

Adult

The ocular ischemic syndrome. III. Visual prognosis and the effect of treatment.

The records of fifty-two consecutive patients with the ocular ischemic syndrome seen between 1978 and 1985 were reviewed with the purpose of investigating the visual prognosis and effects of treatment. On initial presentation, 43% of affected eyes had a visual acuity of 20/20-20/50, whereas 37% were counting fingers or worse. By the end of one year, only 24% remained in the 20/20-20/50 group, while 58% were counting fingers or worse. The presence of rubeosis iridis was an indicator of poor visual prognosis. Ninety-seven percent of eyes with rubeosis had vision of counting fingers or worse at the end of one year. We were unable to demonstrate convincingly that carotid endarterectomy and superficial temporal artery to middle cerebral artery bypass were of benefit in stabilizing or improving vision in persons with the ocular ischemic syndrome.

Aged