Lecythophora mutabilis endophthalmitis after long-term corneal cyanoacrylate.
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Adult↗
Biomedical subjects
D M Marcus
Publications and source records attributed to D M Marcus.
The effect of blood transfusion protocol on retinopathy of prematurity: A prospective, randomized study.
OBJECTIVE: Controversy exists regarding the potential influence of anemia and blood transfusions on the rate of retinopathy of prematurity (ROP) in premature infants. A prospective, randomized, masked trial was performed to determine the influence of red blood cell transfusion protocol on ROP incidence and severity in a population of high-risk infants. METHODS: A total of 50 infants with birth weights <1251 g were divided randomly into two groups beginning on day of life 29. Group 1 (n = 24) received red cell transfusions during the 6-week study period, only if certain symptom-based guidelines were met. Group 2 (n = 26) received red cell transfusions to maintain the hematocrit level above 40% for the entire 6 weeks. Infants were monitored for ROP, growth, and associated morbidity. Serial measurements of serum glucose, lactate, ferritin, total iron-binding capacity, and iron were performed. RESULTS: ROP occurred in 83% of infants in group 1, and 73% of infants in group 2. There were no statistically significant differences in ROP severity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or any of the laboratory values except hemoglobin (10.8 vs 13.2 g/dL) and hematocrit (33.9% vs 41.8%) between the groups. Combining data from both groups, there was no association between hemoglobin or hematocrit ratios and ROP incidence or severity. CONCLUSIONS: A transfusion policy aimed at limiting the amount of blood given to premature infants (symptom-based) during the neonatal period does not impart a significantly different risk for ROP or other associated conditions, than does a policy in which transfusions are given more liberally for replacement purposes.
Erythrocyte Transfusion↗
Decreased synthesis of glycosphingolipids in cells lacking vimentin intermediate filaments.
We are studying defects in glycosphingolipid synthesis in cells lacking vimentin intermediate filaments (vimentin-). Sugars can be incorporated into glycolipids whose ceramide is synthesized either de novo (pathway 1) or from sphingoid bases salvaged from hydrolysis of sphingolipids (pathway 2) and into glycolipids recycling from the endosomal pathway through the Golgi (pathway 3). Vimentin- embryonic fibroblasts, obtained from vimentin-knockout mice, incorporate less sugar into glycolipids than vimentin+ fibroblasts. Using two inhibitors of ceramide synthesis, beta-chloroalanine and fumonisin B1, we found the major defect in synthesis to be in pathway 2 and not in de novo synthesis. We used two additional approaches to analyze the functions of pathways 2 and 3. First, we used exogenous glucosylthioceramide ([14C]C8-Glc-S-Cer), a synthetic, nonhydrolyzable glycosphingolipid, as a precursor for synthesis of larger glycolipids. Vimentin- SW13 cells and embryonic fibroblasts glycosylated [14C]C8-Glc-S-Cer less extensively than their vimentin+ counterparts. Second, we used chloroquine to inhibit the hydrolysis of sphingolipids in endosomes and lysosomes. Chloroquine markedly decreased the incorporation of sugars into glycolipids larger than glucosylceramide. The defect in glycolipid synthesis in vimentin- cells probably results from impaired intracellular transport of glycolipids and sphingoid bases between the endosomal/lysosomal pathway and the Golgi apparatus and endoplasmic reticulum. Intermediate filaments may accomplish this function by contributing to the organization of subcellular organelles and/or by binding proteins that participate in transport processes.
Animals↗
Telemedicine diagnosis of eye disorders by direct ophthalmoscopy. A pilot study.
OBJECTIVE: To report a pilot study of telemedical direct ophthalmoscopy in the diagnosis of acquired immune deficiency syndrome (AIDS)-related retinopathy in a human immunodeficiency virus (HIV)-positive population and in the diagnosis of glaucoma, cataract, and retinopathy in a diabetic population. DESIGN: Prospective comparative case series. PARTICIPANTS: Seventeen HIV-positive and 20 diabetic patients. METHODS: A direct ophthalmoscope custom-fitted with a digital microcamera capable of transmitting images from any of 61 sites within the Georgia Statewide Telemedicine Program was used by a nonophthalmologist to examine 34 eyes of 17 HIV-positive patients and 39 eyes of 20 patients with diabetes. Fundus images were transmitted in real-time to a reviewing ophthalmologist. An in-person, comprehensive examination including indirect ophthalmoscopy, was performed by a second ophthalmologist. Telemedical examination was compared to the in-person comprehensive examination. RESULTS: For the HIV study, 21 eyes did not show HIV retinopathy (noninfectious retinopathy with cotton-wool spots) by in-person examination. Telemedical examination correctly identified 20 of these eyes as disease-free (specificity = 95%). HIV retinopathy was present in 12 of the 34 eyes by in-person evaluation with telemedical examination correctly diagnosing 10 of these eyes (sensitivity = 83%). One eye with dense cataract and retinal detachment was unable to be evaluated ophthalmoscopically by either in-person or telemedical examination. Telemedical and in-person assessments for HIV retinopathy were identical in 100% of eyes without cataract. Disagreement in diagnosis between telemedical and in-person examination was associated with cataract (P < 0.0007). For the diabetes study, because of an inadequate image, telemedical examination was unable to classify 46% and 36% of eyes for glaucoma and diabetic retinopathy, respectively. Inability to make a telemedical determination for glaucoma (P < 0.011), nonproliferative (P < 0.064) and proliferative (P < 0.064) diabetic retinopathy was associated with cataract. Of the eyes that were able to be assessed by telemedical examination for diabetic retinopathy (n = 25), glaucoma (n = 21), and cataract (n = 39), the accuracy was poor (sensitivity = 29%, 50%, and 41%, respectively). Telemedical examination for diabetic retinopathy and glaucoma was more likely to agree with in-person examination in eyes without cataract as compared to eyes with cataract (not statistically significant). CONCLUSION: Telemedical direct ophthalmoscopic, real-time fundus imaging may provide a valuable means for providing ophthalmic consultation to the primary care physician in younger patients without lens or media opacity, but is inadequate for eyes with any degree of lens or media opacity.
Acquired Immunodeficiency Syndrome↗
Modulation of VEGF production by pH and glucose in retinal Müller cells.
PURPOSE: To investigate the influence of pH and glucose concentration, both of which represent significant biochemical variables in tissue ischemia, on the production of VEGF protein by retinal Müller cells and C6 glioma cells, under normoxic and hypoxic conditions. METHODS: Rat retinal Müller cells and C6 glioma cells grown in tissue culture monolayers were studied. The effect of pH (range 7.0-8.0) and glucose concentration (0.6-25 mmol/L) on VEGF protein production, under both normoxic and hypoxic conditions, were evaluated by ELISA analysis of the conditioned media. Establishment of significant cell hypoxia was verified by measurement of lactate release into the conditioned media. RESULTS: Hypoxia caused a 7.9-fold increase in VEGF production in C6 cells at 24 h, and a 3.4-fold increase in Müller cells after 48 h. Under hypoxic conditions, VEGF protein production was increased further by increasing pH and increasing glucose, and decreased by low pH and low glucose. Varying the glucose concentration or pH of the medium did not result in significant induction of VEGF protein production by either cell type under normoxic conditions. CONCLUSIONS: Both glucose and pH significantly affected VEGF production induced by low oxygen. However, neither exerted a measurable stimulatory effect on VEGF production in normoxic conditions. Coexisting hypoxia and acidosis or hypoglycemia, as might occur in severe tissue ischemia, may render glial cells incapable of effectively upregulating VEGF synthesis, while alkalosis or hyperglycemia may augment hypoxia-induced VEGF production.
Animals↗
Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways.
There are several pathways for the incorporation of sugars into glycosphingolipids (GSL). Sugars can be added to ceramide that contains sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to ceramide synthesized from sphingoid bases produced by hydrolysis of sphingolipids (pathway 2), and into GSL recycling from the endosomal pathway through the Golgi (pathway 3). We reported previously the surprising observation that SW13 cells, a human adrenal carcinoma cell line, synthesize most of their GSL in pathway 2. We now present data on the synthesis of GSL in four additional cell lines. Approximately 90% of sugar incorporation took place in pathway 2, and 10% or less in pathway 1, in human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast, approximately 50-90% of sugar incorporation took place in pathway 1 in C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14 times as much GSL as the other three cell lines. In C6 glioma cells, approximately 30% of sugar incorporation occurred in pathway 1 and 60% in pathway 2. There was no relation between the utilization of pathways for GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In both cells pathways 1 and 2 each accounted for 50% of incorporation of choline into sphingomyelin. In five of the six cell lines that we have studied, most GSL synthesis takes place in pathway 2. We suggest that when the need for synthesis is relatively low, as in slowly dividing cells, GSL are synthesized predominantly from sphingoid bases salvaged from the hydrolytic pathway. When cells are dividing more rapidly, the need for increased synthesis is met by upregulating the de novo pathway.
Carbohydrate Sequence↗
Kinetics of fluid delivery from methylcellulose sponges.
PURPOSE: The authors quantitatively evaluate the kinetics of fluid transfer from microsurgical sponges in a laboratory model to understand the kinetics of mitomycin C (MMC) delivery. METHODS: The amount of fluid transferred from soaked methylcellulose (Weck-cel, Weck Inc., Durham, NC, U.S.A.) sponges to small pieces of hydrated or dry filter paper used to simulate episcleral tissue and Tenon fascia was measured as a function of time, sponge size, hydration status of the filter paper, and technique of sponge application. RESULTS: The time course of fluid delivery from methylcellulose sponges to filter paper was nonlinear and characterized by a rapid delivery phase over the first 15 to 30 seconds, followed by a slow phase extending to at least 5 minutes. Sponge size and baseline hydration of the paper significantly influenced the rate and amount of fluid delivered, as did replacing the sponge every minute with a new sponge. CONCLUSION: The transfer of fluid from a microsurgical sponge displays nonlinear kinetics, with the majority of delivery occurring in the first 15 to 30 seconds. Sponge size, hydration of the recipient tissue, and technique of sponge application are significant variables influencing the amount of fluid, and therefore mitomycin C, delivered.
Antibiotics, Antineoplastic↗
Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption.
OBJECTIVE: To examine eyes from mice with targeted adenomatous polyposis coli (APC) gene disruption to determine if retinal pigment epithelium (RPE) abnormalities replicate the human counterpart. METHODS: Thirty-two eyes from 16 mice heterozygous for APC gene disruption (chain-termination mutation in codon 1638 of exon 15) and 12 control eyes were examined by light microscopy. RESULTS: Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in the areas of outer and inner segments. Retinal abnormalities included outer nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and retinal abnormalities seen in the control eyes. CONCLUSIONS: This study is consistent with the hypothesis that the APC gene is critical in the regulation of RPE proliferation and development. These findings also demonstrate that mutation of the APC gene in codon 1638, a location beyond the previously described critical region for human RPE abnormalities, leads to perturbation in the mouse RPE and retina. Further study of this murine model and the APC/RPE relationship may provide insight into regulatory mechanisms for RPE proliferation.
Adenomatous Polyposis Coli↗
Detection and localization of steel intraocular foreign bodies using computed tomography. A comparison of helical and conventional axial scanning.
PURPOSE: To compare the sensitivity and specificity of detection, and accuracy of localization, of small steel intraocular and episcleral foreign bodies, using conventional axial and helical computed tomographic scanning in an experimental model. METHODS: Small steel foreign bodies ranging in size from 0.048 to 0.179 mm3 were placed in intraocular and episcleral locations in eye bank eyes mounted in the orbits of a human skull and scanned using helical and conventional axial techniques. Helical scanning was performed using 1-mm and 3-mm thick sections. Conventional axial scanning was performed using 3-mm thick sections. Images were reviewed by masked observers to determine sensitivity, specificity, and accuracy of localization for each imaging method. RESULTS: Steel foreign bodies as small as 0.048 mm3 were detectable with each scanning protocol. Although the helical scans appeared to provide higher levels of sensitivity compared to conventional axial scanning, the difference in outcome between the scan types was not statistically significant. Sensitivity was dependent on the size of the foreign body and ranged from 45% to 65% for the smaller ones (< 0.06 mm3) to 100% for the larger ones (> 0.06 mm3). Multiplanar reformatting of images was helpful in achieving optimal accuracy. CONCLUSION: In an experimental model of steel intraocular foreign body, helical computed tomographic scanning provided images of high quality similar to that of conventional axial scanning.
Cadaver↗
On knowing what one knows.
The author presents vignettes of a type of experience that is familiar to many analysts. He suggests that analysts and analysands know much more about each other than is generally recognized and that much of the important communication is subliminal, out of conscious awareness. Evidence of our unconscious knowledge surfaces in the form of emotion, fantasy, images, intrusive thoughts, and physical feelings. Often it seems uncanny. Recent experimental evidence and neurobiological research seem to explain and validate these analytic experiences.
Emotions↗
High affinity antibodies against Lex and sialyl Lex from a phage display library.
Our previous studies of seven murine mAbs against the carbohydrate Lex Ag demonstrated that they were all encoded by VH441 and V kappa 24B. To obtain higher affinity Abs, and to ascertain whether their L chains could be encoded by other genes, we constructed a phage display library in a modified pComb 8 vector. The library contained random L chains, and Fd segments enriched in VH domains encoded by the VHX24 gene family. We selected phage with an Lex-BSA Ag, and obtained two Fab mAbs, clones 23 and 24, whose affinities were more than 100-fold higher than hybridoma mAb PM81. Both new mAbs were encoded by VH441, and their L chains were encoded by genes of the V kappa Ox1 and V kappa 9 families. In contrast to hybridoma mAb PM81, which binds only Lex, clones 23 and 24 bound sialyl Lex (SLex) as well as Lex, and clone 23 also binds the backbone carbohydrate structure nLacCer. Analysis of the binding of these three mAbs to synthetic glycolipids that contained structural modifications indicated that they recognize different aspects of the Lex structure, and suggested that they bind to limited regions of the oligosaccharide.
Amino Acid Sequence↗
An analytical review of silicone immunology.
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Adjuvants, Immunologic↗
Inflammatory opacities of the vitreous in rifabutin-associated uveitis.
PURPOSE: To describe rifabutin-associated uveitis with opacities in the inferior and posterior vitreous in three patients with acquired immunodeficiency syndrome. METHOD: Case reports of the three patients are presented. RESULTS: The patients, who were being treated with rifabutin and fluconazole, developed anterior and posterior uveitis. The posterior uveitis was characterized by white-yellow inflammatory opacities located in the inferior and posterior vitreous. Discontinuation of rifabutin and the start of topical corticosteroid therapy resulted in improvement of the uveitis and visual acuity. CONCLUSION: Recognition of rifabutin-associated uveitis with opacities in the inferior and posterior vitreous may prevent unnecessary invasive diagnostic and therapeutic procedures.
Acquired Immunodeficiency Syndrome↗
Pathways of glycosphingolipid biosynthesis in SW13 cells in the presence and absence of vimentin intermediate filaments.
We reported previously that the incorporation of sugars into glycosphingolipids (GSL) is diminished in SW13 cells that lack a vimentin intermediate filament (IF) network (vim-) compared to vim+ cells. To further analyze the nature of this abnormality, we double-labeled cells with 3H-serine and 14C-sugars. There was no difference between vim+ and vim- cells in the incorporation of serine into GSL, although the usual difference in sugar incorporation was observed. This indicated that the defect in vim- cells was not in the incorporation of sugars into ceramide synthesized de novo by acylation of sphinganine (pathway 1). Sugars can also be incorporated into ceramide synthesized from sphingosine that is derived from catabolism of sphingolipids (pathway 2), and into GSL that recycle through the Golgi apparatus from endosomes (pathway 3). The amount of galactose and glucosamine incorporated into GSL in these three pathways was analyzed by the use of two inhibitors of sphingolipid biosynthesis. beta-Chloroalanine inhibits the de novo synthesis of sphinganine (pathway 1), and fumonisin B1 inhibits the acylation of sphinganine and sphingosine (pathways 1 and 2). We were surprised to observe that in both vim+ and vim- cells only 20-40% of sugar incorporation into GSL took place in pathway 1, and 60-80% of sugar incorporation took place in the recycling pathways. Moreover, in contrast to larger GSL, GlcCer was not synthesized in pathway 3. Our observations indicate that vimentin IF facilitate the recycling of GSL and sphingosine, and that the differences between vim+ and vim- cells are predominantly in pathways 2 and 3. Furthermore, although it is generally believed that virtually all GSL are synthesized in the de novo pathway, these data indicate that the recycling pathways predominate in the incorporation of sugars into GSL in SW13 cells.
Acylation↗
Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen.
PURPOSE: A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. METHODS: Formalin-fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. RESULTS: Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. CONCLUSIONS: Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.
Animals↗
Choroidal and retinal detachment in antineutrophil cytoplasmic antibody-positive scleritis.
PURPOSE/METHODS: A 72-year-old woman with antineutrophil cytoplasmic antibody-positive vasculitis had a combined detachment of the choroid and retina. This unique initial manifestation was also associated with systemic and orbital manifestations, including brow ptosis, dacryoadenitis, and pneumonitis. RESULTS/CONCLUSIONS: This patient underwent vitrectomy for removal of a dense vitreitis and responded well to systemic cyclophosphamide. This case demonstrates that antineutrophil cytoplasmic antibody testing is useful for the diagnosis and treatment of Wegener's granulomatosis and microscopic polyarteritis-associated scleritis. The distinction between these two entities is often difficult to make.
Aged↗
Posterior segment complications after vitrectomy for macular hole.
PURPOSE: The purpose of this study is to assess the rate of posterior segment complications after vitreous surgery for macular holes and to evaluate the effect of such complications on final visual outcome. METHODS: The authors reviewed retrospectively all cases of vitreous surgery for macular holes performed between June 1990 and October 1993. Among 98 patients with a followup of 3 months or more, all patients with posterior segment complications during the postoperative course were identified. The rate of complications was compared with that seen after vitreous surgery for macular pucker performed by the same surgeons. RESULTS: Posterior segment complications were noted in 23 (23%) of 98 patients. These included peripheral retinal breaks (3%), rhegmatogenous retinal detachment from a peripheral retinal break (14%), enlargement of the hole (2%), late reopening of the hole (2%), retinal pigment epithelium loss under the hole (1%), photic toxicity (1%), and endophthalmitis (1%). In 40% of these eyes, the final visual acuity was two lines or more below preoperative visual acuity. When compared with the macular pucker group, the rate of posterior segment complications, in particular the rate of peripheral retinal tears and detachments, was significantly higher (P < or = 0.05). CONCLUSIONS: The authors conclude that visually significant posterior segment complications may occur after vitrectomy for macular hole, and the rate of these complications appears to be higher than expected.
Adult↗
Vitreoretinal management of traumatic dislocation of the crystalline lens.
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Anterior Eye Segment↗