Search PubMed⌕ Search

Biomedical subjects

G A Williams

Publications and source records attributed to G A Williams.

At least 55 records · Page 3Linked to original sources
PubMed1999

Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes.

PURPOSE: Retinal neovascularization is one of the leading causes of blindness. A crucial event in this process is the remodeling and penetration of the capillary basement membrane by migrating endothelial cells. This process requires proteolysis of basement membrane components by a variety of proteinases. The objective of the present study was to determine the expression of proteinases in human retinal tissues showing active neovascularization. METHODS: Epiretinal neovascular membranes surgically removed from patients with proliferative diabetic retinopathy were analyzed by zymography, and the types and amounts of proteinases present in the tissues were determined. Retinas from nondiabetic donor eyes served as control specimens. RESULTS: Both the high- (54 kDa) and low- (33 kDa) molecular-weight forms of urokinase were present at significantly higher levels in neovascular membranes than in normal retinas. The pro forms of the matrix metalloproteinases (MMP) MMP-2 and MMP-9 were significantly elevated in the neovascular membranes in comparison with levels in normal retinas. In addition, the active forms of these enzymes were present in the membranes, whereas there was no detectable level of the active forms in normal retinas. CONCLUSIONS: Human diabetic neovascular membranes contain high levels of urokinase and MMP. The increased activity of proteinases in the final common pathway of retinal neovascularization indicates that inhibition of these enzymes may be a useful therapeutic target as an alternative approach in the management of proliferative retinopathies.

Aged↗
PubMed1998

Comparison of recombinant transforming growth factor-beta-2 and placebo as an adjunctive agent for macular hole surgery.

OBJECTIVE: This study aimed to compare the visual and anatomic results of macular hole surgery in eyes treated with recombinant transforming growth factor-beta-2 (TGF-beta2) or placebo. DESIGN: The design was a prospective, multicenter, randomized, double-masked, placebo-controlled clinical study. PARTICIPANTS: One hundred thirty eyes with idiopathic macular holes of 1 year or less and a refracted Early Treatment Diabetic Retinopathy Study visual acuity of 20/80 or worse were treated with 1.1 microg recombinant TGF-beta2 or placebo to the macular hole after fluid-gas exchange. INTERVENTION: The effect of recombinant TGF-beta2 as an adjunctive agent for macular hole surgery was evaluated. MAIN OUTCOME MEASURES: Closure of the macular hole and change in visual acuity at 3 months were measured. RESULTS: The 3-month visits were completed for 120 eyes. The macular hole was closed at 3 months in 35 (61.4%) of 57 eyes treated with placebo and 49 (77.8%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.08). The mean visual acuity gain was +6.4 letters in eyes receiving placebo and +8.9 letters in eyes treated with recombinant TGF-beta2 (P = 0.27). Visual acuity improved 2 or more lines in 23 (40.4%) of 57 eyes treated with placebo and 30 (47.6%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.42). Intraocular pressure elevation greater than 30 mmHg was more common 2 weeks after surgery in eyes treated with recombinant TGF-beta2 (P < 0.001). CONCLUSIONS: Recombinant TGF-beta2 resulted in a similar proportion of successful closure of macular holes as placebo. There was no statistically significant visual acuity benefit with the use of recombinant TGF-beta2 for the treatment of macular holes.

Aged↗
PubMed1998

Plasmin enzyme-assisted vitrectomy in traumatic pediatric macular holes.

OBJECTIVE: This study aimed to evaluate the benefit of plasmin enzyme-assisted macular hole surgery on a consecutive series of pediatric patients with traumatic macular holes. DESIGN: Prospective noncomparative case series operated on at William Beaumont Hospital between July 13, 1996, and November 16, 1996, and observed for at least 6 months. PARTICIPANTS: During this interval, the authors operated on four eyes from four consecutive patients who were 14 years of age or younger with traumatic macular holes. INTERVENTION: The patients underwent plasmin enzyme-assisted pars plana vitrectomy with membrane peeling, fluid-gas exchange, and postoperative positioning. The enzyme used was 0.4 international unit (IU) of autologous plasmin enzyme. MAIN OUTCOME MEASURES: Snellen lines of improvement in visual acuity and rate of final visual acuity of 20/40 or greater, and incidence of complications and reoperations were measured. RESULTS: All four macular holes were closed successfully. Follow-up was from 6 to 12 months. There were no reoperations. Visual acuity improved from four to eight lines in all eyes. Three eyes (75%) achieved a postoperative visual acuity of 20/40 or better. Three eyes (75%) had transient, posterior, subcapsular cataracts develop: two of the eyes after surgery and one as a result of the initial injury. CONCLUSION: The treatment of pediatric traumatic macular holes with plasmin enzyme-assisted vitrectomy, membrane peeling, and gas-fluid exchange resulted in closure of the macular holes with significant visual improvement.

Adolescent↗
PubMed1998

Good visual acuity in an adult population with marked posterior segment changes secondary to retinopathy of prematurity.

PURPOSE: To show that good visual acuity can be compatible with marked posterior segment changes secondary to retinopathy of prematurity (ROP) in the adult population. METHODS: A retrospective chart review of adult patients with regressed ROP. We found 14 eyes in 12 patients who were older than 21 years with a visual acuity of 20/60 or better associated with marked posterior segment changes secondary to ROP. RESULTS: Of the 14 eyes, 11 were myopic, with six eyes having the spherical equivalent of > or = -6.00. Best-corrected visual acuities ranged from 20/15-20/60. One eye had a macular fold. Thirteen eyes had macular ectopia. CONCLUSIONS: Good vision can be compatible with marked posterior segment changes secondary to ROP in an adult population. This emphasizes the need to follow these patients closely during childhood and treat them promptly for any amblyogenic condition that could prevent them from reaching their full visual potential.

Adult↗
PubMed1998

Adrenoleukodystrophy: unusual clinical and radiographic manifestation.

Adrenoleukodystrophy is an X-linked recessive peroxisomal disorder, characterized by progressive neurologic deterioration due to cerebral white matter demyelination and adrenal insufficiency. Onset is usually in childhood between ages 5 and 10, and its course is fatal within approximately 5 years. Initial symptoms are behavioral, gait, and auditory disturbances and may be a diagnostic dilemma. Abnormally raised plasma very long chain fatty acids (VLCFA) are diagnostic; computed tomography and magnetic resonance imaging findings show symmetrical occipital white matter lesions which progress in a rostralcaudal direction.

Adolescent↗
PubMed1998

Video technology and children's evidence: international perspectives and recent research.

Research has shown that children can be as competent and reliable as adults as eyewitnesses of crime, if questioned in an appropriate manner. However, there is considerable variation between, and within, countries in the way in which child witness evidence is accepted in criminal cases. This article reviews the legal facilities that exist for young witnesses in countries such as the United States, England & Wales, Canada and Australia. Particular emphasis is placed on recent research into the use of video technology by the courts in child abuse cases--namely testimony with a live video link or a pre-recorded interview in place of live, open court evidence. Studies into the use of live link and videotaped interviews have shown that these innovations could help to reduce the trauma of testifying for children and could lead to better quality evidence from the child. However, there is considerable concern among legal and child protection professionals about the relative lack of impact of video testimony when compared with live, in-court testimony. Research has uncovered significant support among legal professionals towards using curtained partitions 'screens' to allow a child witness to testify within the courtroom without allowing the child to see, or be distracted by, the accused. There is also widespread concern about the questioning techniques used in videotaped interviews and with the live link. Future implications for the use of video testimony are also discussed.

Adolescent↗
PubMed1997

Vitrectomy for retained lens fragments after phacoemulsification.

PURPOSE: Posterior lens fragments after phacoemulsification can be a serious complication of cataract surgery. This study is designed to evaluate the clinical features of eyes after pars plana vitrectomy has been performed to remove posteriorly dislocated lens fragments after phacoemulsification. METHODS: The authors performed a retrospective chart review of 126 consecutive eyes of 126 patients with dislocated lens fragments after phacoemulsification, managed with pars plana vitrectomy at Associated Retinal Consultants of Michigan. These eyes were operated on from January 1986 through January 1996. RESULTS: The relation of the intervals between cataract surgery and vitrectomy to various postoperative clinical parameters was studied. Clinical features at presentation included elevated intraocular pressure (IOP over 25 mmHg) in 52.4% of the eyes, uveitis in 69.6%, and corneal edema in 50.8%. Initial visual acuity was 20/400 or worse in 73.8% of the eyes. The mean preoperative visual acuity was 20/278 (median, 20/400), whereas the mean final visual acuity was 20/40 (median, 20/50) after a mean follow-up of 18.9 months. Retinal detachments were found in 20 eyes: 7 before vitrectomy and 13 during or after it. After surgery, 44% of eyes achieved a final visual acuity of 20/40 or better and 90% were 20/400 or better. The distribution of best-corrected final visual acuities among the eyes showed statistically significant differences based on the type of intraocular lens (IOL) used, with posterior chamber IOL greater than anterior chamber IOL, and anterior chamber IOL greater than aphakia. Reasons for a poor visual outcome included persistent corneal edema (four eyes), retinal detachment (two eyes), central retinal vein occlusion (two eyes), age-related macular degeneration (two eyes) glaucoma (one year), and endophthalmitis (one eye). CONCLUSIONS: There were no statistically significant differences between early (< 7 days) and delayed (8 days or more) vitrectomy when increased IOP, corneal edema, choroidal effusions, cystoid macular edema, and visual acuity were analyzed. The use of vitrectomy to remove posteriorly dislocated lens fragments has been shown to be an effective treatment method that significantly reduces the inflammatory response and hastens visual recovery.

Adult↗
PubMed1997

Using focus group methodology to develop breast cancer screening programs that recruit African American women.

Public communication campaigns are designed to increase the number of women who receive mammograms, breast examinations, and cervical exams. However, these campaigns have failed to recruit sufficient numbers of African American women. Focus group techniques were used to provide data to develop a communication campaign that would increase the knowledge, assess the attitudes, and change behaviors of African American women, aged 40-65, about the aforementioned preventive health practices. The discussions revealed that participants distrusted "clinics" and preferred being examined by "their own" or a private physician. Results further revealed that the personal influence of opinion leaders, combined with interpersonal contacts that encourage preventive care, help influence women to participate in mammography and cervical cancer screening.

Adult↗
PubMed1997

Macular hole surgery without using adjunctive additives.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of performing surgical techniques for macular holes without using adjunctive additives. PATIENTS AND METHODS: A prospective study was completed of consecutive eyes treated for macular holes of 1 year or less duration that had not had previous vitreous surgery. The best-corrected visual acuity and hole flattening were determined. RESULTS: Postoperative flattening of the hole was achieved in 39 (91%) of 43 eyes, with at least a 50% reduction of the minimum resolvable visual angle (3-line visual increase) in 65% of the eyes and a final vision of 20/40 or better in 40% of the eyes during the follow-up interval (mean 10.6 months). CONCLUSIONS: The success rate of current macular hole surgical techniques suggests that adjunctive additives may not be necessary for most cases. Thus, new treatment modalities need to be evaluated with carefully controlled studies.

Aged↗
PubMed1995

Stabilization of ribonuclease B activity by concentrated xylose solutions.

Ribonuclease B has become a paradigm as a simple example of an N-linked glycoprotein. We have found that certain affinity-purified preparations of this enzyme demonstrated a pronounced tendency to lose activity if stored as dilute aqueous solutions. Such inactivation is accelerated by the presence of NaCl, but can be counteracted by inclusion of high (1 mol/l) concentrations of xylose. Enzyme activity cannot be restored by addition of xylose after storage of the enzyme. In marked contrast to alpha-methyl-mannoside, xylose does not prevent ribonuclease B from binding to concanavalin A and so may be used to stabilize the enzyme during purification by lectin affinity chromatography.

Chromatography, Affinity↗
PubMed1995

Lens-sparing vitrectomy with perfluorocarbon liquid for the primary treatment of giant retinal tears.

PURPOSE: To evaluate the surgical success of vitrectomy without initial lensectomy in the primary treatment of retinal detachment associated with giant tears without proliferative vitreoretinopathy. METHODS: Thirty-four consecutive phakic eyes with idiopathic giant retinal tears underwent vitrectomy, injection of perfluorocarbon liquid, endolaser, and gas tamponade. Encircling scleral buckling was performed in 14 of 34 patients. Preoperative visual acuity ranged from 20/25 to hand motions. Giant tear size ranged from 90 degrees to 330 degrees. Follow-up ranged from 10 to 64 months. RESULTS: Anatomic retinal re-attachment was achieved intraoperatively in all eyes. The re-operation rate was 14% for eyes that underwent scleral buckling with the initial vitrectomy and 45% in eyes without primary scleral buckling. In 59% of eyes with cataract formation, 32% underwent cataract surgery with or without intraocular lens implantation. Best-corrected final visual acuity ranged from 20/15 to 20/400. CONCLUSION: Most phakic eyes with giant retinal tear not associated with proliferative vitreoretinopathy can be re-attached successfully with initial preservation of the lens.

Adolescent↗
PubMed1994

Alpha-crystallin: molecular chaperone and protein surfactant.

Bovine lens alpha-crystallin has recently been shown to function as a molecular chaperone by stabilizing proteins against heat denaturation (Horwitz, J. (1992) Proc. Natl. Acad. Sci. USA, 89, 10449-10453). An investigation, using a variety of physico-chemical methods, is presented into the mechanism of stabilization. alpha-Crystallin exhibits properties of a surfactant. Firstly, a plot of conductivity of alpha-crystallin versus concentration shows a distinct inflection in its profile, i.e., a critical micelle concentration (cmc), over a concentration range from 0.15 to 0.17 mM. Gel chromatographic and 1H-NMR spectroscopic studies spanning the cmc indicate no change in the aggregated state of alpha-crystallin implying that a change in conformation of the aggregate occurs at the cmc. Secondly, spectrophotometric studies of the rate of heat-induced aggregation and precipitation of alcohol dehydrogenase (ADH), beta L- and gamma-crystallin in the presence of alpha-crystallin and a variety of synthetic surfactants show that stabilization against precipitation results from hydrophobic interactions with alpha-crystallin and monomeric anionic surfactants. Per mole of subunit or monomer, alpha-crystallin is the most efficient at stabilization. alpha-Crystallin, however, does not preserve the activity of ADH after heating. After heat inactivation, gel permeation HPLC indicates that ADH and alpha-crystallin form a high molecular weight aggregate. Similar results are obtained following incubation of beta L- and gamma-crystallin with alpha-crystallin. 1H-NMR spectroscopy of mixtures of alpha- and beta L-crystallin, in their native states, reveals that the C-terminus of beta B2-crystallin is involved in interaction with alpha-crystallin. In the case of gamma- and alpha-crystallin mixtures, a specific interaction occurs between alpha-crystallin and the C-terminal region of gamma B-crystallin, an area which is known from the crystal structure to be relatively hydrophobic and to be involved in intermolecular interactions. The short, flexible C-terminal extensions of alpha-crystallin are not involved in specific interactions with these proteins. It is concluded that alpha-crystallin interacts with native proteins in a weak manner. Once a protein has become denatured, however, the soluble complex with alpha-crystallin cannot be readily dissociated. In the aging lens this finding may have relevance to the formation of high molecular weight crystallin aggregates.

Alcohol Dehydrogenase↗
PubMed1994

Platelet activation during hand vibration.

The level of beta-thromboglobulin, the circulating platelet aggregate ratio and platelet sensitivity to aggregation with adenosine 5'-diphosphate (ADP) and collagen were assessed in 12 control subjects, 16 patients with vibration white finger (VWF) and 15 patients with primary Raynaud's disease; this was done before and after a 1-min exposure to hand vibration. The beta-thromboglobulin level increased significantly in controls, from a median (interquartile range) of 35.5 (22-47) to 47.5 (27-52) ng/ml, and in the VWF group from 44.0 (39-60) to 47.5 (42-109) ng/ml (P < 0.005). Vibration had no effect on circulating platelet aggregate ratio in any group. The platelets of normal subjects tended to be more sensitive to aggregation with low-dose ADP (1 mmol/l) than those of patients with VWF or primary Raynaud's disease. Significant change occurred in the lag phase of the aggregation response to vibration in the control group at an ADP concentration of 2 and 5 mmol/l. These results indicate that intravascular platelet aggregation occurs as a result of exposure to vibration. Platelet sensitivity to aggregation with ADP may be decreased in patients with VWF or established Raynaud's disease.

Adenosine Diphosphate↗
PubMed1994

Determination of the ratios of 239Pu and 240Pu to 241Am for nuclear weapons test sites in Australia.

Recent measurements of the plutonium contamination at former nuclear weapons test sites in Australia have used the 59.5 keV gamma ray from the 241Am impurity to estimate levels of 239Pu and 240Pu. Measurements of the activity ratio of 239Pu to 241Am are presented for sites where suitable samples could be collected. Measurements of 240Pu were also made when interferences from fission products were absent. All measurements were made using a planar Ge detector of sufficient resolution to separate the 51.6 keV 239Pu gamma ray from the Ge K x-ray escape peaks and Compton scattering continuum from the much stronger 59.5 keV 241Am gamma ray. Results are given for most of the plutonium-contaminated sites in Australia.

Americium↗
PubMed1994

Exercise technetium-99m sestamibi tomography for cardiac risk stratification of patients with stable chest pain.

BACKGROUND: This study was designed to evaluate the prognostic value of symptom-limited maximal exercise treadmill testing with tomographic technetium-99m sestamibi (MIBI) myocardial imaging in patients referred for evaluation of stable angina. Exercise stress thallium-201 myocardial imaging provides prognostic information in coronary artery disease subsets including patients with stable chest pain. The prognostic value of exercise technetium-99m MIBI myocardial tomography has not been established. METHODS AND RESULTS: Of 548 consecutive patients with stable angina pectoris who underwent maximal exercise treadmill stress testing in combination with a same-day "rest-stress" tomographic technetium-99m MIBI myocardial imaging protocol, 521 patients were followed for 13 +/- 5 months to determine the univariate and multivariate variables associated with cardiac events and to define their cardiac event-free survival. Ten patients were lost to follow-up (98% complete), and 17 who had coronary revascularization within 6 months of testing were excluded. Major cardiac events occurred in 24 patients (9%)--nonfatal myocardial infarction in 11 and cardiac death in 13. Univariate Cox survival analysis demonstrated significant relative risk (RR) and 95% confidence intervals (CI) for exercise ST segment depression (RR = 2.3; 95% CI, 1.0 to 5.3), an abnormal MIBI scan (RR = 13.8; 95% CI, 1.9 to 102.3), and a reversible MIBI perfusion defect (RR = 3.2; 95% CI, 1.4 to 7.5). Multivariate models demonstrated that both exercise MIBI perfusion abnormalities (RR = 11.9; 95% CI, 1.6 to 89.4) and reversible MIBI perfusion defects (RR = 2.9; 95% CI, 1.2 to 7.0) had independent predictive value. During 1 year of follow-up, cardiac events occurred in only 0.5% of patients with normal MIBI scans compared with 7% of those with abnormal MIBI scans (P < .001). One-year, cardiac event-free survival was 92% in patients with reversible MIBI perfusion defects (P < .01 versus normal), 96% in patients with fixed defects (P < .01), and 93% in patients with combined reversible and fixed MIBI myocardial perfusion abnormalities (P < .02). CONCLUSIONS: As with exercise thallium-201 myocardial imaging, exercise stress technetium-99m MIBI myocardial tomography provides significant independent information concerning the subsequent risk of serious cardiac events (death, myocardial infarction) in patients with stable angina pectoris. The identification of MIBI perfusion abnormalities, in particular, the presence of reversible MIBI defects, was associated with reduced 1-year, event-free survival. The recognized imaging and radiotracer biokinetic differences between thallium-201 and MIBI do not appear to modulate the prognostic value associated with scintigraphic evidence of ischemic myocardial jeopardy in the stable angina population.

Chest Pain↗