Search PubMed⌕ Search

Biomedical subjects

B M Elliott

Publications and source records attributed to B M Elliott.

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

Adult vs. adolescent rats differ in biobehavioral responses to chronic nicotine administration.

More than 90% of smokers begin smoking during adolescence, suggesting that nicotine's actions may differ in adults vs. adolescents in ways that render adolescents vulnerable to smoking initiation. This experiment tested the hypothesis that nicotine's biobehavioral actions differ in adult and adolescent rats. Forty-two male (21 adolescents, 21 adults) and 41 female (21 adolescents, 20 adults) Sprague-Dawley rats were administered saline or 12 mg/kg/day nicotine via osmotic minipump for 21 days. Body weight, feeding, and locomotion (horizontal activity, vertical activity, center time) were measured before, during, and after saline or nicotine administration. Nicotine's effects depended on age and sex. Nicotine reduced body weight and feeding of adult males and females, and of adolescent males, but not of adolescent females. In addition, adolescent males were more sensitive than adults or adolescent females to nicotine's activity-enhancing effects. In cessation, nicotine-exposed adolescent males continued to exhibit greater activity than saline-exposed animals. Results indicate that nicotine's biobehavioral actions differ depending on age and sex.

Aging↗
PubMed2001

The mutagenic potential of acetonitrile in the bone marrow and peripheral blood of the mouse.

Acetonitrile was tested for its ability to induce clastogenic or aneugenic effects through the induction of micronucleated polychromatic erythrocytes (MNPCE) in mouse bone marrow and peripheral blood. Groups of NMRI mice, five males and five females, were administered a single i.p. dose of acetonitrile, corresponding to the maximum tolerated dose (MTD), 100 or 125 mg/kg body wt for males and females, respectively. Bone marrow was sampled at 18, 24 or 36 h after treatment, while peripheral blood was sampled before and 24, 48, 72 and 96 h after treatment. Positive controls were administered cyclophosphamide (65 mg/kg i.p.). Acetonitrile did not increase the incidence of MNPCE in either bone marrow or peripheral blood in male mice or in peripheral blood in females. A small, but statistically significant (P: < 0.05), increase was observed in female bone marrow 36 h after administration, but since this was within the range of the control data it is not considered to be of biological significance. Cyclophosphamide increased the incidence of MNPCE in bone marrow and peripheral blood of both sexes. It is concluded that acetonitrile is neither clastogenic nor aneugenic in the bone marrow of the mouse at the MTD.

Acetonitriles↗
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↗
PubMed1998

An assessment of the genetic toxicology of antimony trioxide.

Antimony trioxide (Sb2O3, CAS 1309-64-4) has been examined in a range of in vitro and in vivo genotoxicity assays. Negative results were obtained with the Salmonella/microsome assay and the L5178Y mutation assay, but a positive response was observed in the in vitro cytogenetic assay using isolated human peripheral lymphocytes. However, in vivo, antimony trioxide was non-clastogenic in the mouse bone marrow micronucleus assay, following oral gavage administration for 1, 7, 14 or 21 days at dose levels of up to 5000 mg/kg (single dose) or 1000 mg/kg (repeat dose). A negative result was also obtained in the in vivo rat liver DNA repair (unscheduled DNA synthesis) assay following a single oral gavage administration of doses up to 5000 mg/kg. These data show no genotoxicity for antimony trioxide in vivo and do not confirm a previous report of clastogenicity in the mouse on repeated dosing. It is concluded that antimony trioxide is not genotoxic in vivo and does not present a genotoxic hazard to humans.

Animals↗
PubMed1998

Assessment of developmental effects, cytotoxicity and genotoxicity in the marine polychaete (Platynereis dumerilii) exposed to disinfected municipal sewage effluent.

While sodium hypochlorite is widely used as a disinfectant for municipal sewage effluents and power station cooling waters discharged into coastal environments, there is limited information on the potential in vivo genotoxicity of such disinfection procedures to marine organisms. Using a recently developed test system based on the marine polychaete Platynereis dumerilii, we have evaluated impacts based on embryo-larval development, cytotoxicity and genotoxicity following exposure to disinfected settled (primary) effluent from a municipal sewage treatment works (STW). Sewage samples were collected from Newton Abbot STW, Devon, UK and then disinfected with sodium hypochlorite based on standard operational procedures. Exposure of polychaetes to dilutions of disinfected sewage in seawater (20 +/- 1 degree C) led to a marked reduction in normal embryo-larval development (7 h EC50 from 0.57-1.88% (v/v), n = 4), with a simultaneous increase in cytotoxicity. Following the calculation of the Maximum Tolerated Dose (MTD), based on developmental and cytotoxic effects, the organisms were also analysed for the induction of chromosomal aberrations. This investigation demonstrated the absence of genotoxicity in polychaetes exposed in vivo to sewage disinfected with sodium hypochlorite. These observations extend our previously published studies in which polychaetes exposed to non-disinfected sewage, while showing developmental toxicity and cytotoxicity, did not exhibit any evidence of cytogenetic damage.

Animals↗
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

Short-term growth in asthmatic children using fluticasone propionate.

BACKGROUND: Inhaled corticosteroids may reduce short-term growth velocity in asthmatic children and knemometry is the most sensitive tool to detect this short-term growth suppression. STUDY OBJECTIVE: To compare lower leg growth velocity, as measured by knemometry, in asthmatic children during and after treatment with inhaled fluticasone propionate (FP), 100 microg twice daily. DESIGN: Nonrandomized open trial. SETTING: University hospital, outpatient clinic for pediatric pulmonology. PATIENTS: Twenty-one asthmatic children (13 boys), aged 6 to 10 years. INTERVENTIONS: Inhalation of FP from a dry powder inhaler, 100 microg, twice daily for 6 weeks, followed by 2 weeks during which only an inhaled beta2-agonist was used on demand (washout). During treatment and washout periods, patients were seen every 2 weeks at the same time of day. MEASUREMENTS AND RESULTS: Lower leg growth velocity measured by knemometry during FP treatment was not significantly different from that during washout (p=0.33, one-way analysis of variance). CONCLUSIONS: No significant suppression of lower leg growth velocity was found in prepubertal asthmatic children using FP, 100 microg, by dry powder inhaler twice daily for 6 weeks.

Administration, Inhalation↗
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

Evaluation of the genotoxicity of municipal sewage effluent using the marine worm Platynereis dumerilii (Polychaeta: Nereidae).

Samples of settled (primary) effluent were collected from a municipal sewage treatment works at Newton Abbot, Devon, UK, a site which discharges primary effluent via long sea pipeline into the English Channel (minimum of 200-fold initial dilution). Sewage samples were collected during the period February-April 1995 and were analysed for standard physico-chemical parameters (ammonia, chemical oxygen demand, conductivity, non-purgeable organic carbon and settled solids). Samples were also tested for cytotoxicity, genotoxicity, and for developmental effects in the embryo-larval stages of the marine worm, Platynereis dumerilii. Exposure to sewage concentrations of > or = 10% (v/v) in seawater at 20 +/- 1 degrees C led to a marked reduction in normal embryo-larval development (7 h EC50 values from 10% to 18% v/v, n = 5). There was also evidence of a simultaneous delay in the cell cycle progression (as determined by sister chromatid differential staining) following embryo-larval exposures to sewage concentrations of > or = 10% (v/v). Following the calculation of the Maximum Tolerated Dose (MTD), based on cytotoxic and developmental effects, cells from the same embryo-larvae were analysed for chromosomal aberrations (CAs). Results were consistent for all samples tested, demonstrating the absence of cytogenetic damage following the in vivo exposure of polychaete embryo-larvae to settled sewage.

Animals↗
PubMed1997

The genetic toxicity of time: importance of DNA-unwinding time to the outcome of single-cell gel electrophoresis assays.

Single-cell gel electrophoresis assays (comet assays) are described in which DNA damage is assessed in mouse skin keratinocytes treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and beta-propiolactone (BPL) either in vitro or in vivo. The positive results observed under both conditions of test encourage the further development of the mouse skin comet assay as a screen for direct-acting in vivo genotoxins. From the outset of the present experiments we were struck by the compacted nature of the DNA in mouse skin keratinocytes. Under similar conditions of assay, rodent hepatocytes presented a uniform 'unwound' distribution of DNA over the whole nuclear region. In order to study this effect we varied what seemed to be the most obviously related assay parameter: the DNA-unwinding time. A series of experiments was conducted in which control and MNNG-treated cells were exposed to a range of alkaline DNA-unwinding times (0.3-18 h) followed by measurement of the three comet tail parameters (length, DNA content, and their product, tail moment). Each of these parameters increased with increasing time of unwinding such that the tails observed for MNNG-treated cells with 0.3 h of DNA unwinding were similar in length to the tails of control cells exposed to an 8 h DNA-unwinding time. It is concluded that DNA-unwinding time is a critical parameter of the comet assay and that it may require optimisation for each tissue/cell type studied. Further, the data alert to the prospect that agents that uniquely affect chromosomal protein superstructure may increase comet tail length/DNA content in the absence of chemically induced DNA damage. Thus, there may be two discrete classes of chemical interaction with chromosomal DNA that yield identical comet assay results, but which have different implications for the genetic toxicity of the test agent. Similar effects were observed for rat hepatocytes or mouse lymphoma cells exposed to an 18 h DNA-unwinding time, but no comet tails were produced by exposure of cells to the lysis conditions (pH 10.0) for 18 h.

Acetone↗
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↗