Management of idiopathic macular holes.
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Biomedical subjects
Publications and source records attributed to M A Thomas.
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Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the formation of intracellular cholesterol esters in various tissues. We recently reported the cloning and expression of human macrophage ACAT cDNA. In the current study, we report the production of specific polyclonal antibodies against ACAT by immunizing rabbits with the recombinant fusion protein composed of glutathione S-transferase and the first 131 amino acids of ACAT protein. Immunoblot analysis showed that the antibodies cross-reacted with a 50-kDa protein band from a variety of human cell lines. These antibodies immunodepleted more than 90% of detergent-solubilized ACAT activities from six different human cell types, demonstrating that the 50-kDa protein is the major ACAT catalytic component in these cells. In multiple human tissues examined, the antibodies recognized protein bands with various molecular weights. These antibodies also cross-reacted with the ACAT protein in Chinese hamster ovary cells. Immunoblot analysis showed that the ACAT protein contents in human fibroblast cells, HepG2 cells, or Chinese hamster ovary cells were not affected by sterol in the medium, demonstrating that the main mechanism for sterol-dependent regulation of ACAT activity in these cells is not change in ACAT protein content. As revealed by indirect immunofluorescent microscopy, the ACAT protein in tissue culture cells was located in the endoplasmic reticulum. This finding, along with earlier studies, suggests that cholesterol concentration in the endoplasmic reticulum may be the major determinant for regulating ACAT activity in the intact cells.
BACKGROUND: The development of a thick submacular hemorrhage usually carries a poor visual prognosis. The surgical removal of submacular blood may improve the otherwise poor outlook in these cases. SUBJECTS AND METHODS: Forty-seven consecutive patients underwent vitrectomy with surgical removal of submacular hemorrhage. The patient population consisted of two consecutive groups. Group 1 (1989 to 1991) included 23 patients (20 with age-related macular degeneration [ARMD], one with idiopathic submacular hemorrhage, one with presumed ocular histoplasmosis syndrome [POHS], and one with angioid streaks) who underwent mechanical clot extraction. Group 2 (1991 to 1993) included 24 patients (19 with ARMD, two with POHS, two with arterial macroaneurysm, and one with angioid streaks) who underwent tissue plasminogen activator-assisted drainage of thick submacular hemorrhage. The dose of tissue plasminogen activator ranged from 10 to 40 micrograms. All patients had surgery within 72 hours of diagnosis. RESULTS: In group 1, the mean size of the submacular hemorrhage was 11 disc areas (range, 1 to 16 disc areas). Mean follow-up was 40 weeks. Mean postoperative visual acuity for eyes with ARMD was 20/200. (Visual acuity improved in six eyes, was stable in seven eyes, and deteriorated in seven eyes.) All three of the eyes without ARMD had visual improvement with a mean postoperative visual acuity of 20/70. Overall, visual acuity stabilized or improved in 13 (57%) of 23 patients and decreased in 10 (43%) patients. In group 2, the mean size of the submacular hemorrhage was 11 disc areas (range, 3 to 16 disc areas). Mean follow-up was 24 weeks. Mean postoperative visual acuity for eyes with ARMD was 20/480 (visual acuity was stable in 15 eyes, improved in two eyes, and deteriorated in two eyes). Four of five eyes without ARMD had visual improvement and one was stable, with a mean postoperative visual acuity of 20/60. Visual acuity stabilized or improved in 22 (92%) of 24 patients and decreased in two (8%). The degree of clot lysis was variable. CONCLUSIONS: Submacular hemorrhage secondary to ARMD has a poor visual prognosis, with or without surgical drainage. The addition of tissue plasminogen activator-assisted clot lysis does not appear to significantly improve the visual outcome following surgery. The determination of whether surgical intervention is appropriate in these cases requires a prospective, randomized clinical trial.
Three-dimensionally localized versions of several two-dimensional NMR sequences have been implemented on a 1.5 T whole-body MRI/MRS scanner. In addition to the localization of voxels, the slice-selective RF pulses were also used for refocusing/transfer of various coherences in the 2D NMR sequences. Initial phantom and in vivo human studies are presented here. The sequences were localized versions of 2D J-resolved, 2D zero-quantum, 2D double-quantum, zero-quantum-filtered COSY and SECSY, and double-quantum-filtered COSY and SECSY. Two-dimensional plots for the J-resolved and multiple-quantum sequences are presented for a phantom containing an aqueous solution of 10 mM alanine. Sensitivity of different multiple-quantum-coherence orders to B0 inhomogeneity is discussed. Localized double-quantum-filtered COSY of a phantom containing physiological concentrations of several metabolites also is presented to demonstrate the feasibility of performing this technique within time limits reasonable for human comfort. The first-reported 2D J-resolved 1H in vivo MR spectrum localized in three dimensions in presented here, acquired predominantly from the cerebral white matter of a healthy volunteer and demonstrating the use of localized 2D NMR techniques in vivo.
A two-dimensional (2D) J-resolved MR spectroscopy sequence (2D J-PRESS), fully localized in three dimensions, has been implemented on a whole-body MR scanner. A modified PRESS sequence with [90 degrees-180 degrees-t1/2-180 degrees-t1/2-acquisition] was used for voxel localization. An incremental delay (t1/2) was added to the intervals before and after the last slice-selective 180 degree RF pulse to monitor the J-evolution in a localized 2D MR spectrum. Spectra were recorded with phantoms containing common cerebral metabolites--alanine, N-acetyl aspartate, glutamine, glutamate, taurine, myo-inositol, glucose, aspartate, GABA, and choline at 50 mM. In conformity with previously reported results, additional cross-peaks due to strong coupling were monitored in many metabolites. A brain phantom was developed to mimic the gray matter of human brain with the metabolites at physiological concentrations (0.5-12 mM). In vivo 2D J-PRESS spectra (n = 18) of healthy human brain were in conformity with those recorded from the brain phantom.
PURPOSE: To report the postoperative finding of a dense, permanent, peripheral temporal visual field defect in the treated eyes of three patients who underwent pars plana vitrectomy with air/fluid exchange. METHODS: The patient's charts were reviewed. RESULTS: Visual field loss after pars plana vitrectomy and air/fluid exchange occurs and may be caused by mechanical trauma to the optic nerve head. CONCLUSION: Great caution is advised when aspirating directly over the optic nerve with any extrusion instrument.
PURPOSE: To evaluate the occurrence of cataract formation after pars plana vitrectomy and gas-fluid exchange in patients younger than 50 years of age. METHODS: Twenty-eight patients younger than 50 years of age with bilaterally symmetric crystalline lenses underwent pars plana vitrectomy and gas-fluid exchange in one eye. Postoperatively, lens photographs were used to assess any asymmetry between the surgical and nonsurgical eye. Lens photographs were graded by three independent masked observers using the Lens Opacities Classification System III (LOCS III). Significant cataract progression was defined as either cataract extraction in the surgical eye or a greater than a 0.9 LOCS III unit difference in lens opacity between the surgical and nonsurgical eye. Results were compared with 28 patients older than 50 years of age who had undergone identical surgery. RESULTS: In only 7% of patients younger than 50 years of age (mean age, 36.5 years; range, 16-47 years) did significant lens opacity develop in the surgical eye compared with the nonsurgical eye during the follow-up period (mean follow-up, 25.4 months; range, 12-43 months). Of patients older than 50 years of age (mean age, 68.2 years; range, 51-85 years), 79% developed significant lens opacity in the surgical eye compared with the nonsurgical eye during the follow-up period (mean follow-up 27.3 months; range, 12-49 months). The difference in cataract progression between patients younger than 50 years of age and patients older than 50 years of age was statistically significant (P < 0.0000001). CONCLUSION: Pars plana vitrectomy with gas-fluid exchange is minimally cataractogenic within the first few years in patients younger than 50 years of age.
BACKGROUND: Submacular membranectomy has been suggested as an alternative treatment for subfoveal choroidal neovascularization (CNV). Clinicopathologic features of the right eye of a 59-year-old man with recurrent subfoveal CNV who underwent submacular membranectomy after two unsuccessful laser photocoagulation treatments are reported. METHODS: The surgically excised subfoveal membrane was sectioned serially and evaluated by light microscopy. The globes were obtained postmortem and serial sectioned through the macula and optic nerve head for light microscopy. Ultrastructural study of a tissue section in the center of the lesion was performed. RESULTS: Histopathologic study of the surgically excised membrane disclosed a thin two-component fibrovascular membrane with the larger component internal to residual retinal pigment epithelium and basal laminar deposit. Photoreceptor outer segments were present on the internal surface of the membrane near one margin. Light and electron microscopic study of the postmortem globe revealed a very thin subfoveal subretinal pigment epithelial fibrovascular membrane with loss of photoreceptor cell layer in a central 0.5 mm area, loss of outer segments, reduction of inner segments, and thinning of the outer nuclear layer in the remainder of the lesion. There was moderate retinal pigment epithelial attenuation and mild basal laminar and basal linear deposits. CONCLUSION: Submacular membranectomy for recurrent subfoveal CNV secondary to age-related macular degeneration after two unsuccessful laser photocoagulation treatments appeared to be effective with repopulation of two thirds of the area of membranectomy by extension of attenuated retinal pigment epithelium from adjacent areas. There was, however, persistence or recurrence of CNV, moderate atrophy of the overlying retina with total loss of the photoreceptor cells over the central 0.5 mm of the membrane, and moderate loss of the photoreceptor cells over the remaining area.
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OBJECTIVE: To assess the anatomic outcome and visual acuities at follow-up after pars plana vitrectomy in the management of stage 2 macular holes. DESIGN: Retrospective. SETTING: Retina Consultants, Ltd, St Louis, Mo. PATIENTS: Thirty-three patients, aged 43 to 75 years, with stage 2 macular holes. INTERVENTION: Total pars plana vitrectomy with separation of the posterior hyaloid membrane and injection of intraocular gas followed by postoperative face-down positioning. MAIN OUTCOME MEASURES: Visual acuity and anatomic appearance of the macular hole. RESULTS: Postoperatively, 20 (61%) of 33 eyes attained a visual acuity of 20/50 or greater. Twenty (61%) of 33 eyes showed an improvement in visual acuity, while nine (27%) of 33 were stable. Four (12%) of 33 eyes showed a decline in postoperative visual acuity with progression to a stage 3 macular hole. Twenty-five (76%) of 33 eyes showed stabilization or improvement in the appearance of the macular hole. CONCLUSIONS: Pars plana vitrectomy in conjunction with postoperative intraocular gas tamponade may result in visual and anatomic stabilization or improvement in eyes with stage 2 macular holes. However, because of limited natural history data, it is unknown whether these results are any better than those that might occur without surgery.
PURPOSE: The authors report their experience with the surgical removal of subfoveal choroidal neovascularization. Correlations between preoperative characteristics and final postoperative visual acuity are explored. METHODS: A retrospective study of 159 consecutive patients was performed between February 1990 and August 1993. Follow-up of 2 or more months was available for 147 eyes: presumed ocular histoplasmosis syndrome, 67 eyes; age-related macular degeneration, 41 eyes; myopia, 10 eyes; multifocal choroiditis, 9 eyes; idiopathic, 8 eyes; angioid streaks, 4 eyes; and miscellaneous, 8 eyes. RESULTS: Sixty-seven eyes had presumed ocular histoplasmosis syndrome: mean follow-up was 10.5 months. Visual acuity was stable or improved in 56 (83%) eyes and 20/40 or greater in 21 (31%) eyes. Mean interval to best visual acuity was 3 months. A recurrence rate of 37% had no significant effect on final visual outcome (P = 0.952). Forty-one eyes had age-related macular degeneration: mean follow-up was 15 months. Visual acuity was improved in only five (12%) eyes and was 20/40 or greater in only two (5%) eyes. The interval to best visual acuity was 5 months. A recurrence rate of 27% had not significant effect on final visual outcome (P = 0.31). The visual results and recurrence rates for eyes with less common disorders are presented. CONCLUSION: The surgical excision of subfoveal choroidal neovascularization may stabilize or improve visual acuity in selected cases. Patients with focal disorders of the retinal pigment epithelium-Bruch's membrane complex appear to have a better surgical outcome than those with diffuse disease.
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PURPOSE: To compare the rates of intraoperative and postoperative complications of external argon laser choroidotomy and needle drainage techniques during scleral buckle procedures for primary retinal detachment. METHODS: A group of 175 patients undergoing scleral buckling for primary retinal detachment was randomly assigned to undergo either external argon laser choroidotomy or needle drainage. Complications associated with drainage of subretinal fluid were categorized as retinal break, retinal incarceration, or hemorrhage (dot, < or = 1 disc diameter [DD], or > 1 DD), and recorded during surgery and 24 hours after surgery. RESULTS: In the group that underwent laser choroidotomy, 12 (13%) of 92 patients had complications, including 4 dot hemorrhages, 3 hemorrhages 1 DD or smaller, 3 hemorrhages larger than 1 DD, 1 retinal incarceration, and 1 suprachoroidal hemorrhage. In the group that underwent needle drainage, 13 (16%) of 81 patients had complications, including 3 dot hemorrhages, 4 hemorrhages 1 DD or smaller, 5 hemorrhages larger than 1 DD, and 1 suprachoroidal hemorrhage. No significant difference was noted between the two groups in the incidence of complications (P = 0.657). CONCLUSION: External argon laser choroidotomy and needle choroidotomy are comparable, safe, and effective ways to drain subretinal fluid during scleral buckle surgery.
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The development of subfoveal choroidal neovascularization is a major cause of visual loss in age-related macular degeneration and other disorders of the retinal pigment epithelium-Bruch's membrane complex. We designed a new subretinal laser delivery system and used it to treat subfoveal neovascular membranes in three eyes with age-related macular degeneration. Preoperative visual acuities were 20/200, 20/80, and 20/300, respectively. With a mean follow-up of seven months, postoperative visual acuities were 20/80, 20/400, and 20/300, respectively. One eye developed recurrent neovascularization, which was adequately treated with slit lamp-delivered laser photocoagulation. Another eye continued to lose visual acuity because of progressive atrophy of the retinal pigment epithelium. Although ablation of choroidal neovascular membranes was possible with this technique, visual results were disappointing, probably because of damage of the underlying retinal pigment epithelium and choriocapillaris.
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We prospectively evaluated the effect of interferon alfa-2a on subfoveal choroidal neovascularization. Eight patients with recurrent subfoveal choroidal neovascularization after surgical excision and 12 patients with subfoveal choroidal neovascularization without previous surgical excision received interferon alfa-2a (3.0 to 6.0 million U/m2 of body surface area), every other night for an average of 12 weeks. Mean follow-up was nine months. Visual acuity improved in two of 20 (10%), remained stable in seven of 20 (35%), and worsened in 11 of 20 (55%) patients. The fluorescein angiogram improved in two of 20 (10%), remained stable in three of 20 (15%), and deteriorated in 15 of 20 (75%) patients. All patients had side effects, which led to the discontinuation of therapy in five of 20 (25%) patients. Side effects included flulike symptoms, leukopenia, thrombocytopenia, increased liver enzymes, alopecia, fever, nausea, and suicidal depression. Interferon alfa-2a failed to improve visual acuity or the fluorescein angiographic appearance of subfoveal neovascular membranes in 90% of cases and was associated with marked side effects. We discourage the widespread use of interferon alfa-2a in the treatment of choroidal neovascularization.
To assess the role of brain catecholamines in cognitive decline associated with sleep deprivation, 40 healthy male volunteers were randomized to conditions of total sleep deprivation or 40.5 h of rest. Within each sleep condition, subjects were further randomized to treatment with a 2-day regimen of placebo or alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor. Cognitive performance was measured repeatedly over time using a computerized performance assessment battery. Treatment with AMPT or treatment with sleep deprivation increased sleepiness without producing marked or consistent deterioration in performance. By contrast, subjects who received both treatments reported greater sleepiness than those receiving either treatment alone, and developed severe cognitive impairment on a variety of tasks. These findings, along with previous evidence that catecholamine-enhancing drugs improve performance in sleep-deprived individuals, support the view that decline in cognitive performance during sleep deprivation may be mediated by brain catecholamines.