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Biomedical subjects

C Kon

Publications and source records attributed to C Kon.

15 recordsLinked to original sources

Macular hole surgery without prone positioning.

PURPOSE: To investigate the role of vitrectomy without prone posturing in the anatomic and functional outcome of macular hole surgery (MHS). METHODS: Forty-one consecutive eyes of 41 patients with stage II-IV full-thickness macular holes underwent pars plana vitrectomy and 16% C3F8 tamponade. In 25 cases posturing group (P), subjects were instructed to assume prone positioning for 10 days postoperatively, whereas in 16 cases non-posturing group (NP) patients were advised to avoid lying supine but no other posturing instructions were given. Preoperative, intraoperative and postoperative clinical data were collected, with macular hole closure rate and change in LogMAR visual acuity, contrast sensitivity, metamorphopsia, and 25-Visual Function Questionnaire (VFQ-25) being the primary outcome measures. RESULTS: Over a mean follow-up of 4.21.2 months, anatomical hole closure was noted in 22/25 (88%) and 14/16 (87.5%) in groups P and NP respectively. Visual acuity improved by a mean of eight letters and there was no significant difference in the two groups (P=0.724). Similarly, postoperative prone posturing did not have an effect on the final contrast sensitivity, metamorphopsia, and VFQ-25 composite scores (P=0.238, P=0.472, and P=0.87, respectively). However, eyes in group NP developed significantly more severe cataract in the early postoperative period (P=0.02). CONCLUSIONS: Prone posturing following MHS provides no functional or anatomic benefit but it is associated with slower progression of cataract. Combined phacovitrectomy without face down positioning may be considered for all phakic patients undergoing MHS.

Aged↗

Transpupillary thermotherapy for the treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Prospective, non-randomized, non-masked, case-selected series. METHODS: All patients with subfoveal CNV due to AMD and initial visual acuity (VA) between 6/9 and 6/60 were offered the opportunity to undergo TTT. Recruited subjects were treated using a diode laser (810 nm) with a beam size of 1.2-3.0 mm and power settings of 460-1200 mW. Treatment was applied for 60 seconds in a subthreshold manner. MAIN OUTCOME MEASURES: Differences in VA and changes in the angiographic appearance of CNV. RESULTS: Thirty-one occult/predominantly occult and five classic/predominantly classic membranes were treated with TTT and were followed-up for a mean of 6.0 +/- 1.2 months. Following an average of 1.5 +/- 0.7 (range 1-4) laser sessions, VA remained stable ( -1 to +1 Snellen line) in 24 (66.7%) eyes, improved by > 1 line in two (5.6%) eyes and decreased significantly (> or = 2 Snellen lines) in 10 (27.8%) eyes. Angiographically confirmed closure of CNV was detected in 22 (61.1%) patients. Membranes persisted in 11 (30.6%) eyes and recurred in three (8.3%) eyes. There was no association between reduction, elimination or persistence of angiographic leakage of CNV and change in VA after treatment (p = 0.347). CONCLUSIONS: Transpupillary thermotherapy may be effective at preserving vision and reducing CNV leakage in a number of patients with exudative AMD. Further studies are required to compare TTT with the natural course of subfoveal CNV and alternative treatment options.

Aged↗

Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity.

BACKGROUND: Oral mucosal wounds are characterized by rapid re-epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. OBJECTIVES: To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. METHODS: Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expression and protein production were studied in three-dimensional collagen lattices using quantitative competitive reverse transcriptase-polymerase chain reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymography and reverse zymography. RESULTS: Oral mucosal fibroblasts exhibited increased levels of the 62-kDa active form of MMP-2 and lattice contraction when compared with skin fibroblasts. Oral mucosal and skin fibroblast MMP-2 gene expression and synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT-PCR, zymography and ELISA. Differential MMP-2 activation was, however, related to phenotypic differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. CONCLUSIONS: These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.

Adolescent↗

Phenylephrine and pilocarpine in the treatment of post-operative irido-corneal adhesion.

Following cataract surgery, entrapment of the iris within the surgical wound is often managed by intensive use of miotics. As the radial fibres stretch, only a small amount of fraction is exerted upon the entrapped iris. Application of a combination of phenylephrine and pilocarpine drops causes simultaneous contraction of the pupil sphincter and the radial muscle fibres. This study investigated the relative magnitude of forces induced in the iris periphery by pilocarpine and phenylephrine and the effectiveness of adding g. phenylephrine 10% to g. pilocarpine 4% drops in the treatment of postoperative irido-corneal adhesions. The investigation was divided into two parts. First, the forces induced in the iris periphery upon exposure to pilocarpine and phenylephrine were measured in 6 cadaver irises. The mean force was 27.5 +/- 5.7 x 10(-3) N for pilocarpine and 23.3 +/- 4.0 x 10(-3) N for phenylephrine. The combination of the two drugs produced a force of 54.2 +/- 6.6 x 10(-3) N (p < 0.05). In the second part of the study intensive pilocarpine 4% drops were administered to 17 patients who had iris-wound entrapment on the first post-operative day. Patients with persistent adhesion were commenced on intensive g. phenylephrine 10% and assessed after 90 minutes. Of the 17 patients, 6 responded to pilocarpine drops alone; in a further 7 the irido-corneal adhesion was released only by the addition of phenylephrine drops, and in 4 patients drops were ineffective in relieving the adhesion. This study indicates that addition of phenylephrine 10% to pilocarpine 4% drops enhances the effectiveness of pharmacological treatment of post-operative irido-corneal adhesion.

Cataract Extraction↗

Glutamine and glutamate metabolism in normal and heat shock conditions in Drosophila Kc cells: conditions supporting glutamine synthesis maximize heat shock polypeptide expression.

We have previously reported that Drosophila Kc cells require glutamine for maximal expression of heat shock proteins in stressed conditions (Sanders and Kon: J. Cell. Physiol. 146:180-190, 1991). The mechanism of this effect has been investigated by comparing the metabolic utilization of glutamine in conditions which support hsp expression with that of glutamate in conditions where up to 100-fold less hsp is synthesized. This comparison showed that free ammonia was generated by cells incubated in the presence of glutamine in 37 degrees C (heat shock) conditions, but not at 25 degrees C, and not in the presence of glutamate in either normal or heat shock conditions. There was no difference in the amount of [14C]O2 generated from either [14C]-labeled amino acid in the tricarboxylic acid cycle, but three- to four-fold more alanine was synthesized in cells incubated in glutamine than in glutamate. Treating the cells with aminotransferase inhibitors to artificially increase NH3 release raised hsp expression in the presence of glutamate to maximal levels characteristic of glutamine. This potentiation correlated with inhibition of alanine aminotransferase. Since only NH3 production correlated with hsp expression in heat shock conditions in the presence of glutamine, and NH3 addition to glutamate also resulted in maximal hsp expression, we measured glutamine production in glutamate plus NH3 and observed net glutamine synthesis. The supposition that glutamine itself is responsible for the regulatory changes supporting maximal hsp expression was supported by the finding that the glutamine analog, 6-diazo-5-oxo-L-norleucine (DON), mimicked the effects of glutamine. We conclude that glutamine imposes regulatory changes which alter nitrogen metabolism and support hsp expression in Kc cells.

Amino Acids↗

Glutamine is a powerful effector of heat shock protein expression in Drosophila Kc cells.

We have investigated the effects of extracellular anions on the regulation of expression of the heat shock response in Drosophila Kc cells incubated in defined balanced salt solutions. Widely varying chloride concentrations had no effect on normal or heat shock protein (hsp) expression. Increasing glutamate concentrations from zero to 15 mM increased hsp expression more than 100-fold while affecting expression of non-heat-shock proteins minimally. Glutamine was 20-100-fold more potent than glutamate in supporting hsp expression, while other amino acids were less effective or supported no detectable hsp synthesis in heat shock. Inhibition of glutamine synthetase with methionine-sulfoximine resulted in very low hsp expression with glutamate and normal high level expression with glutamine, confirming the importance of glutamine. The absence of glucose and treatment with 2-deoxyglucose did not change the requirement for adequate glutamine for hsp expression. Cells heat shocked under conditions which gave very low hsp expression resumed growth when returned to normal medium as well as cells which expressed normal levels of hsps. Measurements of free amino acid levels in cells heat shocked in the presence and absence of glutamine showed a correlation between glutamine levels and amount of hsp expression. We conclude that a physiological process regulated by glutamine or a glutamine metabolite is important for normal hsp expression in heat shock conditions in Drosophila.

Amino Acids↗

Mutants of PC12 cells with altered cyclic AMP responses.

PC12 cells, derived from a rat pheochromocytoma, were mutagenized and selected in media containing agents known to elevate intracellular concentrations of cyclic AMP (cAMP). More than 40 clones were isolated by selection with cholera toxin or 2-chloroadenosine or both. The variants that were deficient in accumulating cAMP were obtained by using a protocol in which 1 microM 8-bromo-cAMP was included in addition to the agonist. Certain of these variants were partially characterized with respect to the site of altered cAMP metabolism. The profiles of adenylate cyclase activity responsiveness of certain variants to guanosine-5'-(beta, gamma-imido) triphosphate and to forskolin resembled those of UNC and cyc phenotypes of S49 lymphoma cells, which are functionally deficient in the GTP-sensitive coupling protein, Ns. Other variants were characterized by increased cyclic nucleotide phosphodiesterase activity at low substrate concentration. Diverse morphological traits were observed among the variants, but it was not possible to assign them to a particular cAMP phenotype. Two revertants of a PC12 mutant were isolated and observed to have regained a cellular cAMP response to 2-chloroadenosine and to forskolin. It is hoped that these PC12 mutants will have utility for defining cAMP-mediated functions, including any links to the action of nerve growth factor, in cells derived from the neural crest.

2-Chloroadenosine↗

Potentiation of guanosine 3':5'-monophosphate accumulation in C-6 glial tumor cells.

C-6 glial tumor cells treated with norepinephrine and sodium azide accumulated cyclic GMP to concentrations approximately 10-fold greater than the sum of the separate responses. Isoproterenol, but not phenylephrine, was an effective substitute for norepinephrine, and the response was blocked by propranolol and sotalol. Nitroprusside, but neither cyanide nor isobutyl-methylxanthine, replaced azide. The potentiation was not affected by removal of CA2+ OR Na+ from the extracellular medium and was not blocked by cocaine. The potentiative accumulation of cyclic GMP in C-6 cells differs from the recently described stimulation by catecholamines of soluble guanylate cyclase of renal cortex. The potentiative phenomenon is compared with the few known instances in which cyclic AMP augments cyclic GMP formation and may be associated with synergistic modifications of cellular functions.

Adenylyl Cyclases↗

Systemic conditions in the Emergency Eye Clinic.

PURPOSE: A systemic disease may be diagnosed for the first time in patients who present to the eye department with ophthalmological manifestations. This study documents the pattern of systemic disorders which were encountered in an emergency eye clinic for the first time. SUBJECTS AND METHOD: Over a period of six months details of all patients who had a previously unknown systemic condition diagnosed in the Emergency Eye Clinic were recorded. Patients were seen in this clinic upon referral from other practitioners. All patients, with the exception of those with minor ophthalmic problems, were screened for hypertension and glycosuria. The patients were subsequently referred to their general practitioner or the appropriate hospital specialist for further management. RESULTS: During this period 1025 new patients visited the emergency eye clinic. Previously undiagnosed systemic disease was present in 86 patients (8.4%). The commonest disorders were neurological 35 (41%), cardiovascular 17 (20%), glycosuria 13 (15%) and respiratory 5 (6%). Visual disturbance and pain were the most frequent ocular presentation. In 54 patients (62.8%) the ocular condition was a direct manifestation of the systemic condition and in 32 patients (37.2%) the systemic disease was a coincidental finding. CONCLUSIONS: Awareness of ophthalmological manifestations of systemic disorders helps in the early diagnosis of these conditions and reduces the resulting morbidity and possibly mortality. This study illustrates the hidden role of the emergency eye clinic in identifying patients with an underlying systemic condition.

Brain Diseases↗