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Biomedical subjects

M A Thomas

Publications and source records attributed to M A Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Visual outcome after surgical removal of choroidal neovascularization in pediatric patients.

OBJECTIVE: To assess the visual outcome after surgical removal of choroidal neovascularization (CNV) in pediatric patients. METHODS: A retrospective, noncomparative, consecutive case series of 17 eyes undergoing surgical removal of CNV of various causes in patients aged 18 years and younger. RESULTS: The cause of the CNV was presumed ocular histoplasmosis syndrome in 11 eyes, idiopathic in 3, and optic nerve coloboma, ocular toxoplasmosis, and trauma in 1 eye each. Two eyes had CNV within 100 microm of the center of the foveal avascular zone (juxtafoveal CNV) and 1 eye had peripapillary CNV, while 14 eyes had CNV beneath the geometric center of the foveal avascular zone (subfoveal CNV). In eyes with subfoveal CNV, median preoperative Snellen visual acuity was 20/200 (range, 20/80-3/200). With a median follow-up of 27 months (range, 6-45 months), median final visual acuity was 20/50 (range, 20/20-2/200); 10 (72%) had improvement of 2 or more Snellen lines after surgery, and 6 eyes (43%) had final visual acuity of 20/40 or better. In 3 eyes with juxtafoveal CNV or peripapillary CNV, all eyes had improvement of 4 or more Snellen lines. Postoperative recurrent CNV developed in 6 (35%) of 17 patients; 2 of the eyes underwent a second vitrectomy and 4 received laser treatment for the recurrences. CONCLUSIONS: Pediatric patients may have good recovery of vision after surgical removal of CNV, and the removal of these membranes may be a viable alternative to laser photocoagulation in pediatric patients.

Adolescent↗
PubMed2000

Subretinal surgery for choroidal neovascularization in patients with high myopia.

OBJECTIVE: To analyze the visual outcome in patients undergoing surgical removal of subfoveal choroidal neovascularization (CNV) in eyes with high myopia. METHODS: We retrospectively reviewed the medical records of 48 consecutive patients with high myopia (> or =6 diopters [D]) who underwent vitrectomy with surgical removal of subfoveal CNV. The patient population consisted of 2 groups. Group 1 included 23 patients with findings only of myopic degeneration, and group 2 included 25 patients with presumed ocular histoplasmosis syndrome and myopia of 6 D or more. RESULTS: In group 1, the visual acuity improved by 2 or more Snellen lines in 9 eyes (39%), decreased in 8 eyes (35%), and remained unchanged in 6 (26%), with a mean follow-up of 24 months (range, 8-60 months). The preoperative visual acuity was 20/40 or better in only 1 eye (4%), but 8 (35%) achieved a final visual acuity of 20/40 or better. In group 2, the visual acuity improved in 16 eyes (64%), was stable in 4 (16%), and deteriorated in 5 (20%), with a mean follow-up of 18 months (range, 6-44 months). Only 3 eyes (12%) had a preoperative visual acuity of 20/40 or better, but 11 (44%) achieved a final visual acuity of 20/40 or better. Recurrence occurred in 13 (57%) of the 23 eyes in group 1 and in 9 (36%) of the 25 eyes in group 2. Univariate analysis demonstrated a significant relation between younger patient age (group 1) and absence of postoperative CNV recurrence (group 2) and an improvement of visual acuity (P<.01). CONCLUSIONS: Surgical removal of CNV may provide visual benefit in selected cases of subfoveal CNV associated with high myopia. The determination of whether surgical intervention is appropriate in these cases requires a prospective, randomized, clinical trial.

Adolescent↗
PubMed2000

Submacular surgery to remove choroidal neovascularization associated with central serous chorioretinopathy.

PURPOSE: To report the results of submacular surgery for removal of choroidal neovascularization associated with central serous chorioretinopathy. METHODS: Ten eyes of nine consecutive patients with central serous chorioretinopathy and subfoveal or juxtafoveal choroidal neovascularization underwent pars plana vitrectomy with removal of the choroidal neovascular membrane between January 1994 and January 1999. RESULTS: All 10 eyes (nine patients) were followed postoperatively for at least 6 months. The mean postoperative follow-up was 23 months (range, 6 to 56.5 months). The patients were followed for an average of 6.2 months from the time of symptoms to the removal of the choroidal neovascularization. Preoperative mean best-corrected visual acuity was 20/100 (range, 20/25 to 20/400), and postoperative best-corrected mean visual acuity was 20/60 + 2 (range, 20/20 to 20/400). Seven eyes had improved postoperative visual acuity, with an average of 3.4 lines gained. Of the three eyes that had worse acuity, an average of 1.3 lines of visual acuity was lost; final mean postoperative visual acuity was 20/80 + 1 (range, 20/25 to 20/400). Of the six eyes with symptoms of less than 3 months' duration, four had a final visual acuity of 20/50 or better. All three eyes with 20/300 or worse final visual acuity had loss of foveal retinal pigment epithelium after surgery; the remaining eyes had preserved retinal pigment epithelium with a visual acuity of 20/70 or better. Two eyes had intraoperative peripheral retinal tears, and two eyes had recurrence of the choroidal neovascular complex. CONCLUSIONS: The anatomic and visual results in eyes with choroidal neovascularization associated with central serous chorioretinopathy are modestly encouraging and suggest that submacular surgery for choroidal neovascularization in patients with central serous chorioretinopathy is a treatment option that may salvage good macular function in some eyes.

Adult↗
PubMed2000

Open retinotomy after submacular surgery.

PURPOSE: To report persistent open retinotomy after submacular surgery in patients with presumed ocular histoplasmosis. METHODS: Retrospective review. Five eyes of 5 patients with submacular choroidal neovascularization associated with presumed ocular histoplasmosis had pars plana vitrectomy, detachment of the posterior hyaloid, and surgical removal of the neovascular complex using the small retinotomy technique. All eyes were followed postoperatively for a mean of 47 months (range, 36 to 73 months). RESULTS: In all 5 patients, the open retinotomy persisted after submacular surgery. No complications were associated with the presence of an open retinotomy. CONCLUSION: Persistence of the retinotomy site may occur after submacular surgery. With follow-up of at least 36 months, no significant complication is associated with an open retinotomy site.

Adult↗
PubMed2000

Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I. Ophthalmic outcomes submacular surgery trials pilot study report number 1.

PURPOSE: To report complications and changes in vision during 2 years of follow-up of patients with age-related macular degeneration assigned randomly to surgical removal or to laser photocoagulation of subfoveal recurrent neovascular lesions in a pilot trial designed to test methods, to refine estimates of outcome rates, and to project patient accrual rates for a larger multicenter randomized trial to evaluate submacular surgery. PATIENTS AND METHODS: Eligible patients with previous laser photocoagulation of extrafoveal or juxtafoveal choroidal neovascularization secondary to age-related macular degeneration were enrolled at 15 collaborating clinical centers. Assignments to treatment arm were made by personnel at a central coordinating center. Adherence to eligibility criteria and treatment assignment was assessed centrally at a photograph reading center. Patients were examined at 3, 6, 12, and 24 months after treatment for data collection purposes. Outcome measures reported include treatment complications, adverse events, requirements for additional treatment, and 2-year changes in visual acuity from baseline. RESULTS: Of 70 patients enrolled, 36 were assigned to laser photocoagulation and 34 to submacular surgery; all were treated as assigned. One patient in each group died before the 2-year examination. Visual acuity was measured at the 2-year examination for 31 of the surviving patients (89%) in the laser arm and for 28 of the surviving patients (85%) in the surgery arm. The 2-year measurements for 36 of the 59 patients (61%) were made by an examiner masked to treatment assignment and to the identity of the study eye. Improvements and losses of visual acuity were observed in both treatment arms; 20 of 31 study eyes (65%) in the laser arm and 14 of 28 study eyes (50%) in the surgery arm had visual acuity 2 years after enrollment that was better than or no more than 1 line worse than the baseline level. Changes in visual acuity and the size of the central macular lesions from baseline to the 2-year examination were similar in the treatment arms. Few serious complications were observed in either arm at the time of initial treatment; serious adverse events were rare. During follow-up, 11 laser-treated eyes and 18 surgically treated eyes had additional intraocular procedures. CONCLUSIONS: The data from this pilot trial suggest no reason to prefer submacular surgery over laser photocoagulation for treatment of patients with age-related macular degeneration who have lesions similar to those studied in this pilot trial. Any clinical trial designed to compare submacular surgery with laser photocoagulation in eyes with age-related macular degeneration and subfoveal recurrent neovascular lesions must enroll several hundred patients in order to reach a statistically valid conclusion regarding differences between these two methods of treatment with respect to either changes in visual acuity or complication rates.

Aged↗
PubMed2000

Update on surgical removal of choroidal neovascularization.

Surgical management of choroidal neovascularization may offer patients with subretinal membranes another therapeutic option. Current techniques allow extraction of subretinal membranes, but not all patients have favorable clinical outcomes with such an approach. This article reviews the current state of subretinal surgery and attempts to summarize those characteristics that may predict good surgical results. Vitreoretinal surgical techniques for the management of subretinal membranes are reasonably well established. Certain characteristics of choroidal neovascularization have been identified that may suggest favorable surgical outcomes; however, no randomized prospective data are yet available to show the role of these procedures. The National Institutes of Health-sponsored Submacular Surgery Trials are designed to determine whether surgery or observation is better for eyes with subfoveal choroidal neovascularization in presumed ocular histoplasmosis syndrome or age-related macular degeneration and in eyes with age-related macular degeneration-associated hematomas.

Choroidal Neovascularization↗
PubMed2000

Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments.

Niemann-Pick type C (NPC) disease is characterized by an accumulation of cholesterol and other lipids in the lysosomal compartment. In this report, we use subcellular fractionation and microscopy to determine the localization of the murine Niemann-Pick C1 (NPC1) protein. Fractionation of mouse liver homogenates indicates that some NPC1 cosediments with lysosome-associated membrane protein 1 (LAMP1)-containing membranes. However, a significant amount of NPC1 is also found in membranes that do not contain LAMP1. Moreover, fractionation of liver membranes and fibroblasts in the presence of a nonionic detergent showed that a fraction of NPC1 cosediments with caveolin-1 in rafts. Immunofluorescence microscopy of cultured mouse fibroblasts showed that NPC1 is found in two morphologically distinct structures. The first population is characterized by large punctate structures that do not colocalize with major organelle protein markers, but do colocalize with filipin and a small fraction of caveolin-1. Examination of these large NPC1-containing compartments using electron microscopy shows that these structures contain extensive internal membranes. The second population is represented by smaller, more diffuse structures, a fraction of which colocalize with LAMP1-positive compartments. Incubation of fibroblasts with low density lipoprotein (LDL) increases colocalization of NPC1 with LAMP1-containing compartments. This colocalization can be further enhanced by treating fibroblasts with progesterone or chloroquine. The results indicate that NPC1 is associated with an unique vesicular compartment enriched with cholesterol and containing caveolin-1, and that NPC1 cycles to LAMP1-positive compartments, presumably to facilitate the processing of LDL-derived cholesterol.

Amino Acid Sequence↗
PubMed1999

The activity of the human interleukin-5 conserved lymphokine element 0 is regulated by octamer factors in human cells.

Interleukin-5 (IL-5) controls the development of eosinophilia and contributes to a number of disease states including asthma. Expression of IL-5 is inducible under tight transcriptional regulation. This requires the contribution of several promoter elements; however, the conserved lymphokine element 0 (CLE0) in particular, is essential for expression of IL-5. In this study, we report the nuclear factors which regulate human IL-5 CLE0 activity in the human cell line PER-117. Using specific antibodies, we identified the transcriptional factors Oct-1 and Oct-2 binding to the 5' region of the CLE0 element. The involvement of Oct factors with CLE0 has not been reported previously in any of the lymphokines. In addition, the CLE0 element also appeared to complex with the transcriptional activator AP-1, consisting of the family members Jun D and Fra-2. We observed the binding of Oct-1 to be constitutive in comparison to Oct-2 and AP-1, both of which were induced in response to cell activation by PMA/A23187. Although the interaction of all three factors with CLE0 was closely linked and overlapping, residues critical to their binding were identified. We demonstrate, using site-directed mutagenesis and cotransfection experiments, that the CLE0 element is indispensable for IL-5 promoter activity and that Octamer factors contribute to the positive regulation of the hIL-5 gene.

Base Sequence↗
PubMed1999

Divalent metal derivatives of the hamster dihydroorotase domain.

Dihydroorotase (DHOase, EC 3.5.2.3) is a zinc enzyme that catalyzes the reversible cyclization of N-carbamyl-L-aspartate to L-dihydroorotate in the third reaction of the de novo pathway for biosynthesis of pyrimidine nucleotides. The recombinant hamster DHOase domain from the trifunctional protein, CAD, was overexpressed in Escherichia coli and purified. The DHOase domain contained one bound zinc atom at the active site which was removed by dialysis against the chelator, pyridine-2,6-dicarboxylate, at pH 6.0. The apoenzyme was reconstituted with different divalent cations at pH 7.4. Co(II)-, Zn(II)-, Mn(II)-, and Cd(II)-substituted DHOases had enzymic activity, but replacement with Ni(2+), Cu(2+), Mg(2+), or Ca(2+) ions did not restore activity. Atomic absorption spectroscopy showed binding of one Co(II), Zn(II), Mn(II), Cd(II), Ni(II), or Cu(II) to the enzyme, while Mg(II) and Ca(II) were not bound. The maximal enzymic activities of the active, reconstituted DHOases were in the following order: Co(II) --> Zn(II) --> Mn(II) --> Cd(II). These metal substitutions had major effects upon values for V(max); effects upon the corresponding K(m) values were less pronounced. The pK(a) values of the Co(II)-, Mn(II)-, and Cd(II)-substituted enzymes derived from pH-rate profiles are similar to that of Zn(II)-DHOase, indicating that the derived pK(a) value of 6.56 obtained for Zn-DHOase is not due to ionization of an enzyme-metal aquo complex, but probably a histidine residue at the active site. The visible spectrum of Co(II)-substituted DHOase exhibits maxima at 520 and 570 nm with molar extinction coefficients of 195 and 210 M(-1) cm(-1), consistent with pentacoordination of Co(II) at the active site. The spectra at high and low pH are different, suggesting that the environment of the metal binding site is different at these pHs where the reverse and forward reactions, respectively, are favored.

Animals↗
PubMed1999

Analysis of the 5' and 3'UTRs in the post-transcriptional regulation of the interleukin-5 gene.

Post-transcriptional regulation is emerging as an important control point in cytokine gene expression. However, the role that it plays in IL-5 gene expression is unclear with some conflicting reports. Here we investigate the importance of post-transcriptional regulation and the role of the 5' and 3' untranslated regions (UTRs) in mIL-5 gene expression. To do this, IL-5 expression from a panel of cDNA constructs was compared. We found it essential to remove the 5' synthetic oligonucleotide tails, introduced during the cloning of the mIL-5 cDNA, when studying IL-5 expression. The presence of these oligo(G) tails acted as potent inhibitors of translation of both SV40 and SP6 transcripts. Furthermore, the length of the tails was found to be critical to the translational efficiency. Taking this into account, we found no evidence to suggest that IL-5 is regulated at the level of mRNA stability or translation efficiency by either the 5' or 3'UTR. These results suggest that post-transcriptional control is not a major factor regulating IL-5 expression.

3' Untranslated Regions↗
PubMed1999

Role of nuclear factor of activated T cells (NFAT) in the expression of interleukin-5 and other cytokines involved in the regulation of hemopoetic cells.

NFAT (nuclear factor of activated T cells) is a transcription factor that plays a role in the regulation of various cytokines, including those involved in the regulation of hemopoetic cells such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL4), interleukin-3 (IL3), interleukin-13 (IL13) and interleukin-5 (IL5). In this report we provide a summary of the various locations in the promoters of each of these cytokines where NFAT has been shown or suggested to bind, and at which sites NFAT has been shown to be involved in transcriptional regulation. We also provide experimental data to show that the binding of NFAT to the nucleotides GAA at positions -113 to -111 of the human IL5 promoter is associated with functional activity in human T cells.

Animals↗
PubMed1999

Intraoperative acetazolamide in the prevention of intraocular pressure rise after pars plana vitrectomy with fluid-gas exchange.

PURPOSE: To assess the effect of intraoperative acetazolamide (Diamox) on postoperative intraocular pressure (IOP) in gas-filled, vitrectomized eyes. METHODS: We conducted a prospective randomized clinical trial of 63 consecutive patients undergoing pars plana vitrectomy with total fluid-gas exchange and long-acting intraocular gas tamponade. Patients were randomized by a blind draw to receive either intravenous 500 mg acetazolamide (Diamox) (Group 1) or no treatment (Group 2) at the conclusion of the operative procedure. Intraocular pressures at the conclusion of surgery (IOP-1), 4-8 hours following surgery (IOP-2), and on the first postoperative day (IOP-3) were measured using an Oculab Tono-Pen. RESULTS: Patients in Groups 1 and 2 showed similar mean IOP on postoperative day 1 (20.48+/-7.84 mmHg versus 19.89+/-7.89 mmHg). A similar incidence of IOP-2 greater than 30 mmHg (1 versus 3 patients with high IOP) and IOP-3 greater than 30 mmHg (4 versus 3 patients with high IOP) was seen. Patients in Group 1 had a lower mean IOP at 4-8 hours postoperatively (16.25+/-6.47 mmHg) than those in Group 2 (20.13+/-6.33 mmHg). No correlation could be demonstrated between IOP-1 and subsequent IOP. However, IOP on the first postoperative day (IOP-3) was strongly correlated with IOP 4-8 hours after surgery (IOP-2) (P = 0.0001). No protective effect of Diamox could be demonstrated on either IOP-2 or IOP-3. CONCLUSIONS: No protective effect against pressure rise could be demonstrated for intraoperative acetazolamide (Diamox) in the prophylaxis of IOP rise following pars plana vitrectomy and total fluid-gas exchange with long-acting intraocular gas.

Acetazolamide↗
PubMed1999

Validation of linked administrative data on end-stage renal failure: application of record linkage to a 'clinical base population'.

OBJECTIVE: To evaluate the use of record linkage to monitor the occurrence of end-stage renal failure in Western Australia in 1980-94. METHODS: A clinical base population of 1,046 patients was identified from the Western Australian (WA) Health Services Research Linked Database. To exclude acute renal failure, patients were selected if they received in-hospital renal dialysis on more than 10 occasions over more than 28 days in 1980-94. Estimates of annual incident and prevalent cases were validated against the ANZDATA dialysis and transplant register. Reasons for discrepancy were investigated by an ad hoc linkage between the two data sources. RESULTS: The WA Linked Database counted slightly fewer incident cases (-7%) and slightly more prevalent cases (+7%) than the ANZDATA Register. The Linked Database identified 97% of cases on the ANZDATA Register, but this fell to 83% post case definition, probably due to patients receiving home-based dialysis failing to meet our case definition. ANZDATA correctly identified 90% of cases in the linked file. CONCLUSION: Trends in end-stage renal failure from 1986 to 1994, based on the Linked Database, were the same as those reported from purpose-designed disease registers. IMPLICATIONS: Linked administrative data provide a valid and efficient means to plan and evaluate many of the routine aspects of renal dialysis and transplant services.

Adult↗
PubMed1999

Patients' and partners' perceptions of uvulopalatopharyngoplasty for snoring.

OBJECTIVE: Uvulopalatopharyngoplasty (UPPP) has become a routine operation for snoring. Many centres have published their results. Few, if any, have questioned their patient's subjective feelings regarding the operation and more importantly, the patient's partner. METHOD: The study involved postal questionnaires and a retrospective case note review. Between the years 1988 and 1995, 125 patients underwent a UPPP for snoring at Derriford Hospital, Plymouth, England, a large district general hospital. Postal questionnaires were sent to all patients and their partners, asking them about their experience of snoring and of the operation. The subjective postoperative change in the patient's snoring and their day time sleepiness was measured by the Epworth Sleepiness Score. RESULTS: The number of joint questionnaires returned was 90. The number of patients who felt that their snoring had improved after the operation within the first year was 100%, but this fell to 71% after 1 year. There was a significant improvement in the patient's daytime sleepiness after the operation. The list of complications included pain and nasal regurgitation, along with a dry mouth and altered taste. Overall, 78% of patients would recommend the procedure to others. CONCLUSIONS: The operation of UPPP is successful in reducing the severity of snoring noise in the majority of patients, as well as in improving the quality of the patient's sleep. This success, however, decreases with time and must be put in context with the relatively high morbidity.

Adult↗
PubMed1998

Biosynthesis of endotubin: an apical early endosomal glycoprotein from developing rat intestinal epithelial cells.

Endosomes are the site of sorting of internalized receptors and ligands in all cell types and, in polarized cells, the apical endosomal compartment is involved in the selective transepithelial transport of immunoglobulins and growth factors. The biochemical composition of this specialized compartment remains largely unresolved. We have characterized a glycoprotein, called endotubin, that is located in the apical endosomal tubules of developing rat intestinal epithelial cells. A monoclonal antibody against endotubin recognizes a broad band of 55-60kDa, which upon isoelectric focusing can be resolved into two bands, and a faint band of 140kDa. Metabolic labelling followed by immunoprecipitation indicates that endotubin is synthesized as a 140kDa precursor that is cleaved to the 55-60kDa forms. High pH washing of endosomal membranes removes the 55-60kDa forms from the membrane, whereas the high-molecular-mass form remains membrane associated and appears to be an integral membrane protein. Immunoblotting with a polyclonal antibody against the putative cytoplasmic tail of the protein identifies a 140kDa band and a band of 74kDa, presumably the cleavage product. Immunoprecipitation with antibodies against the 55-60kDa form results in coprecipitation of a 74kDa protein, and immunoprecipitation with antibody against the 74kDa protein results in coprecipitation of the 55-60kDa form. Epitope mapping of the monoclonal antibody binding site supports a proposed type I membrane protein orientation. We propose that endotubin is proteolytically processed into a heterodimer with the 55-60kDa fragment remaining membrane-associated through a non-covalent association with the membrane-bound 74kDa portion of the molecule.

Animals↗
PubMed1998

Flip angle effects in STEAM and PRESS-optimized versus sinc RF pulses.

Flip angle dependence of the localized single-voxel 1H NMR spectroscopic sequences STEAM and PRESS using numerically optimized Shinnar-Le Roux (SLR) and conventional sinc RF pulses has been evaluated. Phantom experiments were used to evaluate voxel profiles from MR images of the selected voxels. Information on the total excited volume was recorded from the integrated area under the water peak in the localized spectrum at different flip angles (theta = 0 degrees-180 degrees). The voxel profiles for both the STEAM and PRESS sequences using the SLR RF pulses were found to be identical, unlike the case for the sinc RF pulses. The SLR RF pulses in the PRESS sequence were found to be more sensitive to flip angle variations. Localized, water-suppressed 1H NMR spectra recorded from the frontal gray matter in healthy volunteers (n = 3) showed less lipid contamination using the SLR RF pulses compared with the sinc RF pulses.

Area Under Curve↗