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Biomedical subjects

Robert W Thompson

Publications and source records attributed to Robert W Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2003

Altered patterns of gene expression distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic disease.

OBJECTIVES: The purpose of this study was to profile altered patterns of gene expression that characterize degenerative ascending thoracic aortic aneurysms and to compare these patterns with those observed for infrarenal abdominal aortic aneurysms. METHODS: Full-thickness aortic wall tissues were obtained during surgical repair of degenerative thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms (n = 4 each), with normal thoracic and abdominal aortas from organ transplant donors used as control preparations. Radiolabeled complementary DNA was prepared for each specimen and hybridized to complementary DNA microarrays, and differential levels of gene expression between aneurysmal and normal aortic tissues at each site were assessed by parametric statistics. RESULTS: Of 1185 genes examined, 112 (9.5%) were differentially expressed (P <.05) between thoracic aortic aneurysms and normal thoracic aorta, with 105 increased and 7 decreased. There were 104 genes (8.8%) differentially expressed between infrarenal abdominal aortic aneurysms and normal abdominal aorta (65 increased and 39 decreased). Quantitative increases in expression for 97 genes were unique to thoracic aortic aneurysms, whereas increases for 61 genes were unique to infrarenal abdominal aortic aneurysms. Although 8 gene products were significantly altered in both thoracic and infrarenal abdominal aortic aneurysms, these changes were directionally concordant for only 4 (matrix metalloproteinase 9/gelatinase B, v-yes-1 oncogene, mitogen-activated protein kinase 9, and intercellular adhesion molecule 1/CD54). Results for 9 genes were independently confirmed by quantitative reverse transcriptase-polymerase chain reaction. CONCLUSIONS: Thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms exhibit distinct patterns of gene expression relative to normal aorta from the same sites, with most alterations being unique to each disease. Degenerative aneurysms arising in different locations are thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms.

Adolescent↗
PubMed2003

Long-term graft survival after penetrating keratoplasty.

PURPOSE: To determine long-term graft survival rates and causes of secondary graft failures for a large series of penetrating keratoplasties (PKPs). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Longitudinal review of 3992 consecutive eyes that underwent PKP at a large tertiary care referral center from 1982 through 1996. Data were collected retrospectively from August 1982 through December 1988 and prospectively thereafter. INTERVENTION: Three thousand six hundred forty primary grafts and 352 regrafts. MAIN OUTCOME MEASURES: Corneal graft survival and etiology of graft failures. Patients were evaluated preoperatively and at 1, 3, 6, 9, 12, 18, and 24 months after transplant, then at yearly intervals. RESULTS: Mean recipient age was 67 years (range, 1-98 years). The predominant indications for PKP were pseudophakic bullous keratopathy (32%) and Fuchs' dystrophy (23%). Graft failure occurred in 10% (385) of the eyes. The most common causes of secondary graft failure were endothelial failure (29%) or immunologic endothelial rejection (27%). Survival of first time grafts was 90% at 5 years and 82% at 10 years. Initial regrafts had significantly lower 5-year and 10-year survival rates, 53% and 41%, respectively. The highest 5-year and 10-year survival rates were noted in primary grafts for eyes with a preoperative diagnosis of keratoconus (97% and 92%, respectively), or Fuchs' dystrophy (97% and 90%, respectively). Primary grafts for aphakic bullous keratopathy without intraocular lens placement had the lowest 5-year survival rate, 70%. CONCLUSIONS: The 5-year and 10-year survival rates in this series demonstrate that PKP is a safe and effective treatment for the corneal diseases commonly transplanted in the United States. However, endothelial failure and immunologic graft rejection were persistent risks over the long term, supporting the need for continued patient follow-up. Regrafts, aphakic eyes without intraocular lens placement at the time of transplant, and corneas with deep stromal vascularization had reduced graft survival rates. Pseudophakic bullous keratopathy grafts with a retained posterior chamber intraocular lens were at increased risk of endothelial failure compared with primary grafts done for other causes or compared with pseudophakic bullous keratopathy grafts done with intraocular lens exchange.

Adolescent↗
PubMed2003

Transient exposure to elastase induces mouse aortic wall smooth muscle cell production of MCP-1 and RANTES during development of experimental aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) is associated with chronic transmural inflammation and destruction of the elastic media. The purpose of this study was to elucidate molecular mechanisms that might orchestrate leukocyte recruitment into the outer aortic wall by determining whether CC chemokines contribute to development of aneurysm degeneration in an elastase-induced mouse model of AAA. METHODS: Adult male C57BL/6J mice underwent transient elastase perfusion of the abdominal aorta to induce development of AAA. At various intervals after elastase perfusion (0, 4, 7, 14 days), real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to measure aortic wall expression of the CC (beta) chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T-cell expressed and secreted (RANTES). Expression of these chemokines by cultured mouse aortic smooth muscle cells (AoSMC) was similarly assessed after transient (5 minutes) exposure to elastase solutions in vitro. RESULTS: Mouse aortic diameter (mean +/- SEM) increased to aneurysmal proportions by 14 days after elastase perfusion (from 0.51 +/- 0.03 mm to 1.34 +/- 0.32 mm; 163% increase; P <.05), with macrophage infiltration of the outer aortic wall beginning within 7 to 10 days. Increased aortic wall messenger RNA expression for MCP-1 (28-fold) and RANTES (11-fold) was observed on day 4, with maximal production of chemokine protein on day 7 (MCP-1, from 7.07 +/- 0.06 ng/mL to 19.60 +/- 0.19 ng/mL; P <.001; RANTES, from 0.23 +/- 0.006 ng/mL to 2.03 +/- 0.057 ng/mL; P <.001). Neither MCP-1 nor RANTES was detected in normal mouse aorta with immunohistochemistry, but both chemokines were abundant in AAA. Within 48 hours of transient exposure to elastase, cultured mouse AoSMC exhibited pronounced induction (>90-fold) of MCP-1 and RANTES, despite concomitant decrease in cell numbers. CONCLUSIONS: Increased mouse aortic wall expression of MCP-1 and RANTES occurs early in development of elastase-induced AAA and before onset of the chronic inflammatory response. Moreover, elastase directly stimulates AoSMC chemokine production in vitro. Elastase-induced medial SMC production of CC chemokines may therefore provide an important link between enzymatic injury, leukocyte recruitment, and aneurysmal degeneration of the aortic wall.

Animals↗
PubMed2003

Facial recognition using simulated prosthetic pixelized vision.

PURPOSE: To evaluate a model of simulated pixelized prosthetic vision using noncontiguous circular phosphenes, to test the effects of phosphene and grid parameters on facial recognition. METHODS: A video headset was used to view a reference set of four faces, followed by a partially averted image of one of those faces viewed through a square pixelizing grid that contained 10x10 to 32x32 dots separated by gaps. The grid size, dot size, gap width, dot dropout rate, and gray-scale resolution were varied separately about a standard test condition, for a total of 16 conditions. All tests were first performed at 99% contrast and then repeated at 12.5% contrast. RESULTS: Discrimination speed and performance were influenced by all stimulus parameters. The subjects achieved highly significant facial recognition accuracy for all high-contrast tests except for grids with 70% random dot dropout and two gray levels. In low-contrast tests, significant facial recognition accuracy was achieved for all but the most adverse grid parameters: total grid area less than 17% of the target image, 70% dropout, four or fewer gray levels, and a gap of 40.5 arcmin. For difficult test conditions, a pronounced learning effect was noticed during high-contrast trials, and a more subtle practice effect on timing was evident during subsequent low-contrast trials. CONCLUSIONS: These findings suggest that reliable face recognition with crude pixelized grids can be learned and may be possible, even with a crude visual prosthesis.

Adult↗
PubMed2003

Delayed complications after endovascular AAA repair in women.

PURPOSE: To assess whether women suffer more delayed complications or require more interventions after endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Over a 2-year period, 245 patients (203 men, 42 women) underwent endovascular repair with the AneuRx stent-graft at our institution. Baseline, operative, and follow-up data were reviewed and outcomes compared between men and women for complications or secondary procedures beyond the 30-day postoperative period. RESULTS: The 42 (17.1%) women treated with the AneuRx graft experienced more technical complications (17% versus 8.3%; p<0.05) and acute conversions to open repair (6/7, 86%; p=0.0005). At 30 days, systemic morbidity was significantly higher in women (26% versus 5.3%; p=0.001.) However, mortality (2.3% versus 1.5%), length of hospital stay (2.6 versus 2.9 days), and major endoleaks at discharge (0% versus 1.6%) were similar. Over a mean follow-up of 11.3 months (range 1-26), graft limb occlusion occurred more frequently in female patients (12.2% versus 2.5%; p=0.05), and secondary procedures were required in a significantly higher number of women (29% versus 9%; p<0.05). Three patients in each group (25% of women versus 17% of men) who had secondary procedures required additional interventions. Although not statistically significant, the mortality in women during follow-up was higher (9.7% versus 5%); 2 deaths were directly related to graft complications in the female group. CONCLUSIONS: Endoluminal AAA repair in women presents a technical challenge at the time of operation and may cause more frequent late complications, necessitating close postprocedural surveillance and prompt correction of complications to avoid potentially catastrophic outcomes. Reassessment of inclusion criteria for women may be necessary.

Aged↗
PubMed2002

Treatment of embolizing arterial lesions with endoluminally placed stent grafts.

The purpose of this study was to demonstrate the safety and efficacy of endovascular stent grafts for the management of embolizing arterial lesions. Eight patients who presented to Barnes-Jewish Hospital between June 2000 and June 2001 with embolizing arterial lesions were treated with covered stents or stent grafts. All hospital records were retrospectively reviewed, and pertinent data extracted. Our results showed that endovascular stent grafts can be used successfully to exclude embolizing arterial lesions without increasing the risk of further embolization. Long-term follow-up will be necessary to assess the durability of this approach to embolizing arterial lesions.

Aged↗
PubMed2002

Abdominal aortic aneurysms. Surgical treatment.

The purpose of this chapter is to provide a brief overview of the current place of open surgical repair for abdominal aortic aneurysms with respect to the factors influencing clinical decision-making, the operative techniques most frequently used, and some of the complications commonly encountered in the postoperative period.

Aortic Aneurysm, Abdominal↗
PubMed2002

Monocyte chemotactic activity in human abdominal aortic aneurysms: role of elastin degradation peptides and the 67-kD cell surface elastin receptor.

BACKGROUND: Chronic inflammation is a characteristic feature of abdominal aortic aneurysms (AAAs), but the molecular signals responsible for recruiting monocytes into the outer aortic wall are unresolved. The purpose of this study was to examine whether AAA tissues elaborate chemotactic activity for mononuclear phagocytes and to determine whether this activity is attributable to interactions between elastin degradation peptides (EDPs) and their cell surface receptor, the 67-kD elastin binding protein (EBP). MATERIAL AND METHODS: Soluble proteins were extracted from human AAA tissues, and chemotactic activity for differentiated U937 mononuclear phagocytes was measured by use of a modified Boyden chamber. Chemotactic activity induced by N -formyl-Met-Leu-Phe was used as a positive control and checkerboard analysis was used to distinguish chemotaxis from chemokinesis. Inhibition of chemotaxis was tested by peptide competition, blocking antibodies and galactosugar-mediated dissociation of the 67-kD EBP. RESULTS: AAA extracts stimulated a concentration-dependent increase in monocyte migration that reached up to 24% of the maximal effect induced by N -formyl-Met-Leu-Phe. Checkerboard analysis demonstrated that AAA extracts stimulated chemotaxis without a chemokinetic effect. AAA-derived chemotactic activity was eliminated by competition with Val-Gly-Val-Arg-Pro-Gly (VGVAPG), a repetitive peptide found in human elastin that binds to cellular elastin receptors, and decreased nearly 40% in the presence of BA-4, an antielastin monoclonal antibody that can block EDP-mediated chemotactic activity. Monocyte chemotaxis in response to both VGVAPG and AAA extracts was abolished in the presence of lactose, a galactosugar that specifically dissociates the 67-kD EBP, but it was unaffected by either glucose, fructose, or mannose. CONCLUSIONS: These findings indicate that soluble EDPs released within human AAA tissue can subsequently attract mononuclear phagocytes through ligand-receptor interactions with the 67-kD EBP, thereby providing a plausible molecular mechanism to explain the inflammatory response that accompanies aneurysmal degeneration. Better understanding of factors regulating inflammatory cell recruitment may lead to novel forms of therapy for early stages of aneurysmal degeneration.

Antibodies↗
PubMed2002

Doxycycline in patients with abdominal aortic aneurysms and in mice: comparison of serum levels and effect on aneurysm growth in mice.

OBJECTIVE: Doxycycline has been shown to inhibit aneurysm formation in a rodent model of abdominal aortic aneurysm (AAA). The doses necessary for this inhibition (6 mg/kg) are much higher than the standard antibiotic doses (1 to 1.5 mg/kg) used in humans. Because the side effects associated with doxycycline are dose related, whether patients would tolerate doses that are four to six times higher than normal is unclear. Also unclear is whether the serum levels necessary in these animal models can be safely achieved in patients. The purposes of this study were to determine the serum concentrations necessary to inhibit aneurysm formation in a mouse model of AAA and to compare them with the plasma concentrations in patients with AAA with a standard dose of doxycycline. METHODS: Four groups of 10 mice of C57BL/6 strain were given doxycycline (0, 10, 50, and 100 mg/kg) beginning at 7 weeks of age. At 8 weeks of age, the mice underwent AAA induction through bathing periadventitial aortic tissue with 0.25 mol/L CaCl(2). Blood samples were taken 10 weeks after surgery to assess the levels of doxycycline. Aortic size was measured at AAA induction and at death with a videomicrometer. Fourteen patients with diagnosed AAA were given 100 mg of doxycycline twice a day for at least 3 months. Blood samples to determine the plasma levels of the drug were taken at 3 or 6 months. The circulating levels of doxycycline for mice and humans were assessed with high-performance liquid chromatography. RESULTS: The changes in aortic size and circulating levels of doxycycline in the AAA murine model are reported. Doses of 10, 50, and 100 mg/kg accounted for a 33%, 44%, and 66% reduction of the aneurysmal growth in the mice, respectively. In patients, the circulating doxycycline levels ranged from 1.8 to 9.42 microg/mL (mean, 4.14 +/- 0.557), values similar to those obtained in mice. CONCLUSION: The circulating doxycycline levels of the patients are comparable with those achieved in mice. Doxycycline accounts for an inhibition of 33% to 66% of the aortic growth. The findings suggest that standard doxycycline doses could inhibit AAA growth in humans.

Animals↗
PubMed2002

Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study.

BACKGROUND: The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population. METHODS: Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 +/- 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months. RESULTS: Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 +/- 0.68 ug/mL (median, 3.64 microg/mL; range, 1.31 to 14.39 microg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 +/- 1.3 mm at 6 months versus 41.0 +/- 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% +/- 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 +/- 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 +/- 32.9 ng/mL at 3 months (not significant versus baseline) and to 66.4 +/- 24.2 ng/mL at 6 months (P =.022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P <.05). CONCLUSION: Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

Aged↗
PubMed2002

Incisional refractive surgery.

The use of incisional refractive surgery has become limited due to the widespread use of the excimer laser to correct myopia, hyperopia and astigmatism. Laser in situ keratomileusis and photorefractive keratectomy have proven to be much more accurate and predictable in correcting refractive error. This has made some forms of incisional refractive surgery practically obsolete. Radial keratotomy should not be considered a primary refractive procedure in the modern world, as RK has become "RKhaic". There are still indications for incisional refractive surgery in cataract and post-surgical patients for the treatment of astigmatism. However, with the advent of the toric intraocular lens and the use of LASIK in such aforementioned patients, these indications for incisional surgery will likely become more limited. In this review, we go over the past history of incisional refractive surgery and also report the current uses and advancements of this technique in today's practice environment.

Astigmatism↗
PubMedDate not supplied

Characterization of a recombinant immunodiagnostic antigen (NIE) from Strongyloides stercoralis L3-stage larvae.

Due to the process of internal autoinfection, even chronic asymptomatic infections with Strongyloides stercoralis have the potential to become severe disseminated disease with fatal outcome. Intermittent and scanty larval excretion makes parasitologic diagnosis difficult. Serodiagnosis is helpful, but antigen preparation from infective larvae requires access to patients or immunosuppressed experimental animals. For these reasons, attention has turned to recombinant antigens for immunodiagnosis. A 31-kDa candidate antigen (NIE) derived from an L3 cDNA library is described in this report. Multiple alignment of the deduced amino acid sequence of NIE showed approximately 12-18% identity with various other organisms, including 17.9% of Asp1 of Ancylostoma caninum, 12.6% of Hemonchus contortus, and 17.6% of insect venom allergen 5 of yellow jacket. By ELISA, antibodies to the purified recombinant NIE antigen were demonstrated in 87.5% of 48 sera from strongyloides-infected patients and in only 6.5% of sera from presumed normal controls. Immunoreactivity of purified NIE antigen with parasite-specific IgE from sera of strongyloides-infected patients indicated its potential use as an immediate sensitivity skin test antigen. This application of the NIE antigen was supported by its capacity to trigger release of histamine upon in vitro exposure to blood from strongyloides-infected patients and its failure to produce histamine release from blood of normal controls.

Amino Acid Sequence↗
PubMedDate not supplied

Prospects for the medical management of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a chronic degenerative disease with life-threatening implications. While AAAs are thought to arise through a localized form of arterial wall injury superimposed on various predisposing factors, their natural history is one of progressive structural deterioration, gradual expansion, and eventual rupture. Pathologic processes contributing to the changes observed in AAAs include chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. These changes result in progressive aortic dilatation accompanied by alterations in vessel geometry, redistribution of hemodynamic wall stresses, and diminished tensile strength. As outlined in this review, better understanding of the biological mechanisms underlying these changes will allow design of novel therapeutic strategies to suppress the process of aneurysmal degeneration.

Adrenergic beta-Antagonists↗