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Biomedical subjects

J G Robison

Publications and source records attributed to J G Robison.

At least 19 recordsLinked to original sources
PubMed2001

Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel.

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.

Base Sequence↗
PubMed2001

Contemporary analysis of outcomes following lower extremity bypass in patients with end-stage renal disease.

This study was designed to compare outcomes following infrainguinal bypass between patients with end-stage renal disease (ESRD) and patients with normal renal function (NRF). Sixty-three patients with ESRD undergoing 78 infrainguinal bypasses from 1990 to 1999 were compared with a concurrent group of 132 age-, race-, and gender-matched patients with NRF undergoing 148 bypasses. Limb salvage and survival were calculated using Kaplan-Meier analysis. Markov decision analysis was used to calculate expected quality-adjusted life years (QALY) with intervention. Mean follow-up was 25 months (range 1-116). The results of our study show that infrainguinal bypass in patients with ESRD and tissue necrosis appears to provide a measurable, but marginal, degree of improvement in quality of life.

Adult↗
PubMed2001

A monoclonal antibody specific for human thymidine kinase 1.

Previous research has shown that thymidine kinase 1 (TK1), a nucleotide salvage pathway enzyme, is an accurate prognostic and diagnostic tumor marker. However, the current radioisotope assay for TK1 is cumbersome and has hampered the clinical application of this diagnostic technique in cancer management. To overcome the problems of the current radioisotope assay, we have produced monoclonal antibodies (MAbs) using purified TK1 from Raji cell extract. Production and confirmation of their specificity was confirmed using Western blot, immunohistochemical staining, TK1 activity inhibition assays, and enzyme-linked immunoadsorbent assay (ELISA) techniques. Thus, in the future, these antibodies may aid in the early detection of cancer and more accurate prognosis, as well as allowing for an increased ability to study the function of TK1 in basic cellular processes.

Antibodies, Monoclonal↗
PubMed2001

Thymidine kinase 1 immunoassay: a potential marker for breast cancer.

Previous research indicates that thymidine kinase I (TKI) possesses value as a tool for both prognosis and diagnosis in breast cancer. However, drawbacks to the existing radioassay for thymidine kinase have frustrated its clinical use. To overcome these drawbacks, we developed a monoclonal antibody to TK1. We have assessed this antibody for a linear antibody-antigen response and for reproducibility using ELISA techniques. We also have evaluated this antibody for TKI specificity as determined by Western blot. To test the accuracy of this monoclonal antibody further, we treated human MCF-7 breast cancer cells with tamoxifen and measured decreasing TKI activity and protein levels with the radioassay and with our monoclonal antibody in an ELISA, respectively. We then used the radioassay and our monoclonal antibody to measure TK1 activity and protein levels, respectively, in 218 serum samples of postoperative breast cancer patients and found a correlation between the two assays. Our results demonstrated that the TK1 immunoassay not only had a linear, reproducible, and specific response but accurately measured TK1 levels in both MCF-7 breast cancer cells and serum. Thus, our monoclonal antibody may demonstrate potential for practical use in a clinical setting for the management of breast cancer.

Antibodies, Monoclonal↗
PubMed1999

Diabetes mellitus is the major risk factor for African Americans who undergo peripheral bypass graft operation.

OBJECTIVE: African Americans, especially African American women, have a greater risk of lower extremity ischemia that necessitates an infrainguinal bypass graft operation and amputation. Because the prevalence of diabetes mellitus is proportionally greater in this ethnic/racial group, the relative contribution of diabetes was compared with other potential risk factors. METHODS: This study was designed as a retrospective case control study at the University and Veterans Hospitals. In a 5-year period, 764 consecutive patients who required infrainguinal revascularizations were compared with a statewide population that was described by the 1995 Behavior Risk Factor Surveillance System database. The main outcome measure was the requirement for infrainguinal revascularization. RESULTS: Diabetes mellitus was more common among African American women who underwent bypass graft operation (70%; odds ratio [OR], 24.9; 95% confidence interval [CI], 20.3 to 30.4) than African American men (46%; OR, 11.6; 95% CI, 8.9 to 15.2), white women (49%; OR, 15.9; 95% CI, 13.0 to 19.5), or white men (42%; OR, 14.8; 95% CI, 12.5 to 17.4). Overall, bypass graft operation was associated more strongly with diabetes mellitus for all groups (OR, 15.7; 95% CI, 13.5 to 18. 3) than with smoking (OR, 4.5; 95% CI, 3.8 to 5.2) or hypertension (OR, 4.6; 95% CI, 4.0 to 5.3). Life-table analysis revealed limb salvage to be worse at 3 years among African American patients (64% vs 75%; P <.005) despite similar primary and cumulative secondary graft patency rates. CONCLUSION: Diabetes mellitus is the dominant risk factor that contributes to the need for bypass graft operation, especially among African American women. A greater prevalence of diabetes mellitus may account for the higher incidence of tissue necrosis and the increased requirement for distal bypass grafting and may contribute to the reduction in long-term limb salvage that was observed with these women.

Black or African American↗
PubMed1999

Justification of intervention for limb-threatening ischemia: a surgical decision analysis.

Intervention for vascular occlusive disease of the distal lower extremity in elderly patients will inevitably be scrutinized as medical resources decline. The authors applied surgical decision analysis to three treatment options: revascularization, amputation and expectant management. The appropriate outcome probabilities were derived from our experience with revascularization to the tibial and pedal vessels, and utility scores were obtained by formalized patient assessment. Revascularization was predicted to improve patient outcome by 1.10 quality-adjusted life-years compared with primary amputation and by 1.16 quality-adjusted life-years compared with expectant management. To gain one additional quality-adjusted life-years, revascularization would cost $5280 more than expectant management, but $33,900 less than primary amputation. Sensitivity analysis predicted revascularization to be the least costly treatment per quality-adjusted life-years as long as 1-month patency exceeds 11%. Revascularization for limb-threatening ischemia of the distal lower extremity is justified and can be performed at a reasonable cost.

Aged↗
PubMed1999

The pitfalls of establishing a statewide vascular registry: the South Carolina experience.

Concerned about the inadequacy of a centralized database and the importance of low morbidity and mortality on carotid endarterectomy efficacy, the South Carolina Vascular Surgical Society prospectively instituted a computer registry for carotid procedures performed by its members, to establish a statewide standard of practice. From January 1994 through December 1997, 23 of the 30 physician members voluntarily registered data on 1652 carotid operations at 14 hospitals into a central database. Blinded results were reviewed biannually. Complete data (1995-1997) were available for 1199 cases. The patients tended to be >64 years old (72%), male (62%), and white (93%). Carotid endarterectomy was the most frequently performed operation (90%). Perioperative complications (< or = 30 days) occurred in 173 patients (14.4%), including stroke (n = 19; 1.6%), death (n = 8; 0.7%), and stroke/death (n = 25; 2.0%). Although 23 surgeons (77% of the society) contributed some data, only 10 surgeons (33%) contributed complete data on >10 patients/year. Despite biannual efforts to boost participation, case entry remained stable (1994, 358; 1995, 347; 1996, 425; and 1997, 427), representing about one-third of the estimated carotid procedures performed in the state during that period. The cost of the registry was approximately $11,500. Audit of 8 surgeons revealed a >95 per cent match against the statewide discharge database and low error rate versus independent medical record review. This experience confirms that excellent outcomes after carotid endarterectomy are not limited to a few select centers and can be accomplished by adequately trained surgeons in a variety of institutional settings. Incomplete physician participation, however, inevitably raises questions about the utility of such efforts. Until volunteer registries induce full participation by heightening perceived physician benefit, their role will remain limited for future outcomes research.

Carotid Artery Diseases↗
PubMed1998

Preoperative thromboxane A2/prostaglandin H2 receptor activity predicts early graft thrombosis.

PURPOSE: This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expression of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. A prospective correlation of preoperative platelet TXA2/PGH2 receptor-mediated activity with lower extremity graft patency was sought. METHODS: Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome measures were primary graft patency rate at 3 months, platelet TXA2/PGH2 receptor activity by equilibrium binding with 125I-BOP, and aggregation to the TXA2-mimetic U46619. RESULTS: Preoperative platelet TXA2/PGH2 receptor density was higher (Bmax, 3100 +/- 1300 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 was lower (26 +/- 6 nmol/L vs 57 +/- 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased receptor density. Early graft thrombosis was more likely in patients with a platelet TXA2/PGH2 receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180). CONCLUSIONS: Elevated platelet TXA2/PGH2 receptor levels and enhanced sensitivity of platelet aggregation to TXA2 predict early arterial graft thrombosis. Specific TXA2/PGH2 receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel.

BACKGROUND: Axillary lymph node status in breast cancer patients remains the single most important predictor of outcomes. Current methods of histopathologic analysis may be inadequate because 30% of node-negative patients recur. The purpose of this study was to test the hypothesis that a multigene reverse transcriptase-polymerase chain reaction (RT-PCR) panel provides a more sensitive method to detect axillary lymph node metastases than routine pathologic examination. STUDY DESIGN: Sixty-one consecutive breast cancer patients were evaluated, with nine normal control patients. Nodes > 1 cm were bisected for histopathologic and RT-PCR analysis. Nodal tissue was homogenized, and total RNA was converted into cDNA with reverse transcriptase. Reverse transcriptase-polymerase chain reaction analysis was performed with primers specific for keratin-19, c-myc, prolactin inducible protein (PIP), and beta-actin using ethidium bromide gel electrophoresis. Reverse transcriptase-polymerase chain reaction positive/ pathology negative axillary lymph nodes were reevaluated using step sectioning and immunohistochemical staining. RESULTS: Thirty-seven patients had pathologically negative axillary lymph nodes, of which 15 (40%) were positive by RT-PCR analysis. Two RT-PCR negative results (one probably from tissue processing error and the other secondary to sampling error) among the 24 histologically positive specimens were detected (8%). The number of patients in each pathologic stage was 26 patients in stage I; 18, stage IIA; 7, stage IIB; 7, stage IIIA; 3, stage IIIB; and 0 patients in stage IV. By RT-PCR staging, 8 of 26 patients went from stage I to IIA (30%), and 7 of 18 from stage IIA to IIB (39%). Of the RT-PCR positive individuals who were stage I by pathologic analysis, 100% were found to be c-myc positive, 0% keratin-19 positive, and 0% PIP positive; for stage IIIB patients these markers were 50%, 100%, and 100% respectively. Additionally, an increasing number of positive markers per specimen appeared to correlate with larger primary tumor size (p < 0.01) and decreased predicted 5-year survival (r = 0.950, p < 0.002). CONCLUSIONS: Multimarker RT-PCR analysis appears to be a readily available and highly sensitive method for the detection of axillary lymph node micrometastases. Longterm followup of RT-PCR positive patients will be required to determine its clinical relevance. If validated as a predictor of disease recurrence, this method would provide a powerful complement to routine histopathologic analysis of axillary lymph nodes.

Axilla↗
PubMed1998

Efficacy of reverse transcriptase-polymerase chain reaction screening for micrometastic disease in axillary lymph nodes of breast cancer patients.

Pathologic examination of axillary lymph nodes (ALNs) may miss micrometastases in 30 per cent of breast cancer patients. We have developed a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR)-based screening method that detects histopathologically positive ALNs with a 5 per cent false-negative rate. The purpose of this study was to compare this RT-PCR methodology with histopathology with regard to sensitivity and cost. Pathologically negative ALNs from 35 breast cancer patients were re-evaluated by a single pathologist in a blinded fashion using serial sectioning with immunohistochemical staining. Histopathologic results were then compared with those of RT-PCR. Cost analysis was performed based on standard charges for these methods. RT-PCR identified micrometastases in 14 of 35 pathologically negative nodes. Serial sectioning and immunohistochemical staining identified micrometastases in two cases, with RT-PCR positive for one of these. The charge per specimen for performing routine histopathologic examination was $380, serial sectioning and immunohistochemical staining $787, and RT-PCR $125. RT-PCR appears to be more sensitive at detecting ALN micrometastasis than histopathologic examination even with serial sectioning and immunohistochemical staining. If micrometastatic breast cancer detected by RT-PCR proves to be clinically relevant, it could be a more effective screening methodology with significant cost savings as compared to currently available pathologic examinations.

Adult↗
PubMed1998

Occlusive disease associated with popliteal aneurysms: impact on long term graft patency.

OBJECTIVE: Correlate graft patency and limb salvage outcomes following popliteal aneurysm repair with the extent of tibial occlusive disease. EXPERIMENTAL DESIGN: Retrospective study with a mean follow-up of 36 months (range, 2-96 months). SETTING: Institutional teaching hospital. PATIENTS: Of 20 popliteal aneurysms among 16 patients undergoing repair, 75% were associated with preoperative tibial vessel occlusion. Normal, three vessel infrapopliteal runoff was present in 5 patients, two vessels in 7 patients, and one or no vessels in 8 patients. Fifty percent of limbs were asymptomatic, while the remainder suffered from a variety of ischemic symptoms. INTERVENTIONS: Eighteen of the 20 aneurysms were repaired with femoropopliteal bypass grafts, and two femoral-tibial bypasses were performed. Autogenous saphenous vein was used in 18 cases (10 in situ, 8 reversed) and PTFE in two short segment femoral-popliteal bypasses. MEASURES: Graft patency was determined by presence of a palpable pulse, the re-establishment of normal ankle-brachial indices, or duplex scanning. Patency and limb salvage rates were estimated using life table analysis by the Kaplan-Meier method. RESULTS: Preoperative symptoms did not correlate with tibial runoff, except in two patients presenting with acute thrombosis and ischemia. Cumulative graft patency by life table analysis was not different for either good (2-3 vessels, N-12) or poor (0-1 vessels, N-8) runoff. Overall primary patency at 60 months was 73%, and cumulative secondary patency was 100% with no limbs lost at 60 months. CONCLUSIONS: Concomitant distal arterial occlusive disease is frequently associated with popliteal aneurysms, yet did not appear to substantially impact either long-term graft patency or limb salvage.

Aged↗
PubMed1997

Is duplex venous surveillance worthwhile after arthroplasty?

Deep venous thrombosis (DVT) complicates 60% of knee and 80% of hip arthroplasties performed without prophylactic therapy. Routine postoperative duplex ultrasound surveillance has been proposed for the detection of venous thrombosis following arthroplasty. In order to determine whether surveillance represents an effective strategy to detect postoperative DVT when prophylaxis is used, surveillance duplex exams obtained after primary or revision hip or knee arthroplasty were analyzed using decision analysis techniques. DVT was suspected clinically after 95 of 738 (13%) arthroplasties, with no symptoms suggestive of DVT after the remaining 643 procedures. Surveillance duplex scans were performed within 2 weeks of 371 procedures, while no surveillance studies were performed after the remaining 272 procedures. In these asymptomatic patients only 2 (0.5%) surveillance duplex studies were positive for DVT. In contrast, 4 of 37 (11%) duplex exams and 5 of 62 (8%) contrast phlebograms performed among symptomatic patients were positive for DVT. The overall incidence of DVT after arthroplasty in the entire population was 1.4% (10/738) with no pulmonary emboli. Patient follow-up averaged 162 +/- 285 days. Using the 1995 Medicare reimbursement of $163 for venous duplex, the incremental cost was $35,000 to detect 1 additional unsuspected DVT and $110,000 per additional quality-adjusted life-year gained. The low incidence of clinically significant DVT and pulmonary emboli with current prophylaxis does not justify an aggressive screening program. Decision analysis suggests that a greater incidence of DVT is required for screening to be worthwhile.

Adolescent↗
PubMed1997

Racial differences in operation for peripheral vascular disease: results of a population-based study.

Operation for non-coronary atherosclerotic peripheral vascular occlusive disease may vary among race and gender groups. Using a state-wide registry, the authors identified all operations performed for infrarenal peripheral vascular disease over a 12-month period in a single south-eastern state. Procedures performed included reconstruction for aortoiliac (n=641) and infrainguinal (n=1129) disease and major amputation (n=1077). The incidence for patients over age 50 was calculated using census data. Operation for aortoiliac disease was significantly more likely for white patients (relative risk 3.79, 95% C.I. 2.84-5.15), but less likely for infrainguinal peripheral vascular disease (relative risk 0.64, 95% C.I. 0.56-0.73) and amputation (relative risk 0.17, 95% C.I. 0.15-0.19). Trends toward lower operative mortality in blacks with aortoiliac disease (10.6% versus 12.0%), PVD (3.2% versus 3.5%), and amputation (5.5 versus 8.7%) failed to attain statistical significance. Patient race was associated with the type and location of operation performed for peripheral vascular disease.

Aged↗
PubMed1997

Thromboxane A2 receptor density increases during chronic exposure to thromboxane A2 receptor antagonists after porcine carotid bypass.

Domestic swine (n=12 in each group) were randomized to daily treatment with the thromboxane A2 (TXA2) receptor antagonist BMS-180291 (group I), aspirin (group II), or no drug (group III) prior to prosthetic carotid graft implantation. Platelet and arterial wall receptor density were measured by equilibrium binding using 125I-BOP. At 6 weeks, means (s.e.m.) platelet receptor density (pmol/mg) had increased in groups I (3.3(0.6) versus 1.8(0.3); P<0.05) and II (2.6(0.6) versus 1.7(0.2); P<0.05), but not in group III (1.3(0.3) versus 1.2(0.2)). Aortic membrane TXA2 receptor density (fmol/mg) was significantly greater (P<0.05) in groups I (150(50)) and II (68(10)) compared with group III (39(6)). Chronic exposure to a TXA2 receptor antagonist or aspirin is associated with increased platelet and aortic receptor density in pigs.

Animals↗
PubMed1997

Relevance of quality improvement methods to surgical practice: prospective assessment of carotid endarterectomy.

Continuous quality improvement methods are increasingly being applied to health care systems, yet demonstration of outcome and cost benefits for surgical patients remains sparse. We used continuous quality improvement principles to specifically identify potential opportunities to reduce patient charges for carotid endarterectomy in our academic vascular surgery practice without compromising results. The targeted opportunities included: 1) limitation of laboratory examination, 2) selective cardiac stress testing, 3) discharge on 1st postoperative day, and 4) substitution of outpatient carotid duplex imaging for inpatient angiography. After 1 year, reductions in the average patient charge ($7700 versus $13,900, P < 0.001) and increases in payment/charge ratio (1.2 versus 0.8; P < 0.001) were observed. These changes were primarily due to a reduction in length of stay (2.2 versus 5.7 days; P < 0.001). No significant difference in patient morbidity occurred. Reductions in charges occurred within the targeted areas of laboratory (-77%), cardiac testing (-73%), hospital room (-60%), and radiology (-81%) utilization. Attention to the four factors identified by continuous quality improvement methods significantly reduced total patient charges without detrimental effects on patient outcome.

Aged↗
PubMed1996

Failure of dialysis access: revise or replace?

Providing adequate long-term dialysis access has become increasingly difficult. In order to evaluate the operative factors associated with early failure of dialysis access, 2337 operations performed in 1124 patients over an 8-year period were retrospectively reviewed. Evaluation of 1306 procedures that eventually failed and required operative revision or repair provided the basis for this study. Access failure occurred in 459 (41%) of the 1124 patients. An average of 2.8 episodes of failure (range 1-13) were observed among this group of patients, occurring after an average of 230 +/- 9 days (mean +/- ++standard error) postoperatively, with the longest interval to failure being 2529 days. The time-to-failure for revision of a preexistent arteriovenous fistula or prosthetic graft (140 +/- 9 days, n = 449) was significantly (P < 0.0001 ANOVA) shorter than for creation of an arteriovenous fistula (272 +/- 21 days, n = 336) or prosthetic graft (299 +/- 19 days, n = 372) at a new site. Procedures performed in octogenarians tended to fail earlier (178 days). Dialysis access failure tends to recur in patients with a history of previous access problems. The time-to-failure was similar for new prosthetic grafts and arteriovenous fistulas, but twice as long compared to revision of a previous access site.

Adolescent↗
PubMed1995

Upregulation of b-FGF receptor expression after carotid bypass.

Basic fibroblast growth factor (b-FGF) appears to be an important positive modulator of the neointimal hyperplasia that occurs after prosthetic vascular graft implantation through its effects on vascular myointimal/smooth muscle cell migration and proliferation. The distribution and extent of b-FGF receptor (b-FGFR1) expression was compared using immunohistochemical techniques in normal porcine carotid arteries and at various times up to 6 weeks following implantation of small caliber prosthetic vascular grafts. At the time of graft harvest, specimens were infused with OCT medium at 100 mm Hg and rapidly frozen in liquid nitrogen. Transverse sections of the perianastomotic arterial tissues were labeled with primary mouse monoclonal antibody directed toward the extracellular domain of the receptor, followed by goat-anti mouse IgG and rabbit anti-goat IgG conjugated to horseradish peroxidase. The b-FGFR1-positive cells were identified by peroxidase activity within the Golgi complex of smooth muscle cells. Normal porcine carotid arteries showed no evidence of staining for b-FGFR1. However, at 6 weeks cells in the perianastomotic area clearly showed significant b-FGFR1 localization. Anti-muscle actin labeling confirmed these to be smooth muscle cells. The observed upregulation of b-FGFR1 expression supports the concept of positive feedback by cytokines as a contributing factor to the hyperplastic response of smooth muscle cells after prosthetic vascular graft implantation. This finding further supports a potential strategy to specifically target activated smooth muscle cells through use of mitotoxin therapy.

Animals↗