Search PubMed⌕ Search

Biomedical subjects

B M Elliott

Publications and source records attributed to B M Elliott.

At least 37 records · Page 2Linked to original sources
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

Review of the genotoxicity of 2-butoxyethanol.

The available data on the genotoxicity of 2-butoxyethanol have been reviewed. 2-Butoxyethanol has been examined for genotoxic activity in a range of in vitro and in vivo assays, including the mouse bone marrow micronucleus assay. The in vitro assays used range from well validated and generally accepted assays such as the Salmonella/microsome and in vitro cytogenetic assay, through to less well validated assays such as assessment of the inhibition of metabolic cooperation in V79 cells. The levels of experimental details and data reporting vary across the studies with some papers presenting only limited information. Taking the above factors into consideration, the available data indicate that 2-butoxyethanol has no significant genotoxic activity. This conclusion is also consistent with the chemical structure of 2-butoxyethanol, which is not alerting for likely genotoxic activity. These collected considerations indicate that 2-butoxyethanol is unlikely to be a genotoxic carcinogen to rodents, a prediction that supplements seventeen published predictions of the outcome of the ongoing NTP rodent carcinogenicity bioassays.

Acetaldehyde↗
PubMed1997

CI solvent yellow 14 shows activity in the bone marrow micronucleus assay in both the rat and mouse.

CI Solvent Yellow 14 has been reported to be carcinogenic in the rat, inducing neoplastic liver nodules, but non-carcinogenic in the mouse. The present experiments have extended previously reported investigations on the activity of CI Solvent Yellow 14 in in vivo genotoxicity assays. CI Solvent Yellow 14 has been examined for genotoxicity in vivo in the bone marrow micronucleus assay in both the rat and the mouse, and in the rat liver unscheduled DNA synthesis (DNA repair) assay, to limit doses of 5000 and 2000 mg/kg respectively, by oral gavage. CI Solvent Yellow 14 showed evidence of clastogenic activity in both the rat and mouse bone marrow (clear effect in the rat; weak effect in the mouse), but no evidence of DNA repair in the rat liver. In view of the latter finding, the contribution, if any, of the genotoxicity expressed by the micronucleus assay to the formation of liver nodules on chronic administration of the compound, is unclear.

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

Development of an in vivo genotoxicity assay using the marine worm Platynereis dumerilii (Polychaeta: Nereidae).

An in vivo genotoxicity test system has been developed using the embryo-larval stages of the marine annelid, Platynereis dumerilii (Polychaeta: Nereidae). This species is representative of an ecologically important group of marine invertebrates, it is amenable to laboratory culture and has a well defined and stable karyotype (2n=28) which is suitable for the analysis of a range of cytogenetic endpoints, including chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). An evaluation of the cell cycle kinetics using the embryo-larval stages allowed selection of exposure times for cytogenetic work. Subsequently, 12-h-old embryos were exposed to reference mutagens, dissolved in sea water, in the presence of 5-bromodeoxyuridine (BrdU) for 12 h (SCE analysis) or 8 h (CA analysis) at 15 +/- 1 degree C, by which time they had reached the first larval stage (20-24h). Dose response-relationships for cytotoxicity, SCEs and CAs were observed for both direct acting mutagens (methyl methanesulfonate, mitomycin C) and mutagens which require metabolic activation (cyclophosphamide, benzo[a]pyrene). The sensitivity of the embryo-larval stages of P. dumerilii to both direct and indirect acting mutagens, their suitability for laboratory culture, together with the presence of a good karyotype and chromosome morphology for cytogenetic analyses, makes this species a potentially valuable in vivo model for marine genotoxicity testing.

Animals↗
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↗
PubMed1996

Methyl methanesulphonate (MMS) as a resource conserving and reliable positive control agent for male rat and male mouse dominant lethal assays.

A single i.p. injection of methyl methanesulphonate (MMS; 40 mg/kg) to male rats, followed by their sequential mating over 4-28 days post-dosing, was shown to induce dominant lethal (DL) effects in two strains of rats and in four separate experiments. Activity was evident between 4 days post-dosing (sampling treated spermatozoa) and 28 days post-dosing (sampling treated early spermatids). The highest incidences of resorptions were seen between days 15 and 21 post-dosing, being approximately 1 week later than the peak of activity in the mouse. The DL effects seen were strong and could be detected as early as 4-10 days post-dosing, at which time only small reductions in pregnancy rates and total implantation numbers were seen. Similar, but weaker, mutagenic effects have been reported by Ehling et al. for MMS in mouse DL assays. These data indicate, therefore, that MMS provides a convenient positive control agent for both male rat and male mouse dominant lethal assays, requiring only approximately five treated males, each mated to two females at around 14 days post-dosing.

Animals↗
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↗
PubMed1995

Do results justify an aggressive strategy targeting the pedal arteries for limb salvage?.

We initiated a strategy to bypass all of the significant popliteal and tibial disease in the setting of limb-threatening ischemia beginning in September 1986. Of 194 infrapopliteal bypasses performed for limb salvage during the ensuing 6 years, 111 (57%) autogenous vein bypasses were performed to the pedal vessels at or distal to the ankle. By life table analysis, primary graft patency at 60 months for pedal bypasses was 57%, with salvage of failed grafts resulting in secondary patency of 61%. Limb salvage was 64% at 60 months. Of 33 graft thromboses, 24 (73%) resulted in eventual limb loss. Five limbs were amputated due to wound complications or progressive forefoot sepsis despite patent pedal grafts. More bypasses were performed to the dorsalis pedis than the posterior tibial at the ankle (78 vs 33), but patency and limb salvage were similar. Bypasses to the pedal arteries resulted in superior limb salvage compared with peroneal bypass when forefoot tissue necrosis was present (63 vs 33% at 36 months, P = 0.048). Pedal grafts had comparable overall patency (57 vs 64%) and limb salvage (64 vs 75%) to more proximal tibial bypasses. Pedal bypass provides acceptable long-term outcomes for both patency and limb salvage. When forefoot ischemic tissue loss is present, pedal bypass, when feasible, appears preferable to peroneal bypass.

Diabetes Mellitus↗
PubMed1995

Distal wound complications following pedal bypass: analysis of risk factors.

Wound complications of the pedal incision continue to compromise successful limb salvage following aggressive revascularization. Significant distal wound disruption occurred in 14 of 142 (9.8%) patients undergoing pedal bypass with autogenous vein for limb salvage between 1986 and 1993. One hundred forty-two pedal bypass procedures were performed for rest pain in 66 patients and tissue necrosis in 76. Among the 86 men and 56 women, 76% were diabetic and 73% were black. All but eight patients had a history of diabetes and/or tobacco use. Eight wounds were successfully managed with maintenance of patent grafts from 5 to 57 months. Exposure of a patent graft precipitated amputation in three patients, as did graft occlusion in an additional patient. One graft was salvaged by revision to the peroneal artery and one was covered by a local bipedicled flap. Multiple regression analysis identified three factors associated with wound complications at the pedal incision site: diabetes mellitus (p = 0.03), age > 70 years (p = 0.03), and rest pain (p = 0.05). Ancillary techniques ("pie-crusting") to reduce skin tension resulted in no distal wound problems among 15 patients considered to be at greatest risk for wound breakdown. Attention to technique of distal graft tunneling, a wound closure that reduces tension, and control of swelling by avoiding dependency on and use of gentle elastic compression assume crucial importance in minimizing pedal wound complications following pedal bypass.

Adult↗
PubMed1995

Is infrapopliteal bypass compromised by distal origin of the proximal anastomosis?

Distal origination of the proximal anastomosis (DOPA) of an infrapopliteal bypass beyond the adductor hiatus minimizes the length of graft required and optimizes use of scarce autogenous conduit. Sixty-two DOPA infrapopliteal revascularizations using autogenous vein performed for limb salvage over a 7-year period were reviewed and compared with 203 concurrent infrapopliteal bypasses originating more proximally (POPA). Life-table analysis revealed no difference at 54 months between DOPA and POPA bypass with regard to primary patency (57% vs. 50%, respectively) or secondary patency (67% vs. 65%, respectively). Differences in limb salvage at 54 months between DOPA and POPA bypasses did not reach statistical significance (53% vs. 66%, p = 0.12), although DOPA fared worse. Inferior limb salvage results in all infrapopliteal bypasses were correlated with the presence of tissue necrosis (52% vs. 70%, p < 0.001), which was more prevalent in patients undergoing DOPA bypass (71% vs. 49%, p < 0.01). The long-term patency of infrapopliteal bypass appears only marginally affected by DOPA. However, the prognosis for limb salvage in this setting is compromised as a result of the virulent behavior of the atherosclerotic disease that spares the superficial femoral artery while predominantly involving the popliteal and tibial vessels.

Aged↗
PubMed1995

Protamine use during peripheral vascular surgery: a prospective randomized trial.

PURPOSE: One hundred twenty patients undergoing aortic reconstruction (40), infrainguinal bypass (49), and carotid endarterectomy (31) were prospectively enrolled into a double-blind randomized trial to investigate the utility of routine heparin reversal with protamine. METHODS: All patients underwent systemic heparinization with 90 U/kg body weight during operation and after revascularization were randomized to receive either protamine or saline solution for heparin reversal. Blood loss was measured throughout the surgical procedure, and indexes of coagulation and the requirement for blood and blood products were documented during operation and the first 24 hours after operation. RESULTS: Plasma heparin concentration, partial thromboplastin time, and activated clotting time were significantly higher (p < 0.05) in those receiving saline solution at 20 minutes and 1 hour after administration. Total surgical blood loss was not significantly different between study groups. No significant differences were found in blood product requirement, intravenous fluid administered, hematocrit, or wound hematomas between groups at 24 hours. In addition, no difference was seen in the surgeon's subjective intraoperative assessment of hemostasis after administration of either study drug. Furthermore, after study drug administration protamine was associated with a deleterious effect on subsequent intraoperative blood loss (318 +/- 33 ml vs 195 +/- 18 ml, p < 0.05). CONCLUSIONS: Although protamine effectively reverses heparin anticoagulation, its routine use after elective peripheral vascular surgical reconstruction does not appear to provide any clinical benefit.

Aged↗
PubMed1995

Evaluation of phenobarbital/beta-naphthoflavone as an alternative S9-induction regime to Aroclor 1254 in the rat for use in in vitro genotoxicity assays.

A series of bacterial mutation, mammalian cell (L5178Y) gene mutation and in vitro cytogenetic assays were performed to compare the efficacy of using S9 fractions prepared from rats induced with a combination of phenobarbital (PB) and beta-naphthoflavone (beta NF), with S9 fractions from rats treated with the general enzyme inducer Aroclor 1254. Although some quantitative differences in the magnitudes of the mutagenic/clastogenic effects were observed between the two induction regimes, no qualitative differences were observed. The use of a combined PB/beta NF induction regime using oral dosing is therefore considered to be a suitable substitute for Aroclor 1254.

Administration, Oral↗
PubMed1995

Stratification of mortality risk for renal artery surgery.

Seventy consecutive operations involving the renal arteries were reviewed to identify factors linked to perioperative mortality. Aortorenal bypass (n = 29), endarterectomy (n = 12), extraanatomic bypass (n = 12), thrombectomy (n = 4), and reimplantation (n = 13) were associated with a 16% perioperative mortality that was often secondary to multisystem organ failure. Patients who died exhibited a higher serum creatinine (3.4 vs 2.1 mg/dL; P < 0.05). Stratification of patients by risk revealed higher American Society of Anesthesiologists (ASA) (P < 0.005) and modified Acute Physiology Score, and Chronic Health Evaluation (APACHE II) (P < 0.02) score among patients who died. Higher mortality was also observed after bilateral renal artery operations (31% vs 5%; P < 0.005) or concomitant mesenteric revascularization (37% vs 12%; P < 0.05), but not simultaneous aortic procedures (18% vs 11%; P = NS). Bilateral operation (P < 0.0001), age (P < 0.001), and ASA class (P < 0.01) were independent predictors of mortality according to multivariate analysis. Because of higher mortality in these specific situations, modification or limitation of operative scope may be appropriate.

APACHE↗
PubMed1994

Aortic dissection originating in the suprarenal abdominal aorta.

Spontaneous dissection of the abdominal aorta originating from the suprarenal aorta is very rare. Previous reports attest to the lethal nature of this disorder. This case represents the first report of successful repair of a spontaneous suprarenal abdominal aortic dissection by graft insertion with obliteration of both the entrance tear and the false lumen with reimplantation of the visceral vessels.

Aged↗
PubMed1994

Evaluation of the genotoxicity of 4-diethylamino-4'-nitroazobenzene and seven analogues.

A series of eight nitroaromatic azo compounds based on 4-diethylamino-4'-nitroazobenzene has been examined for genotoxic activity in a collaborative study conducted under the auspices of the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers (ETAD). The evaluation has been conducted in two parts, firstly an examination in vitro to assess any intrinsic genotoxic activity of the compound. The chemicals were examined in the Salmonella assay in a standard plate incorporation protocol in both the presence and absence of S9 and in a minimum of the four tester strains recommended in the OECD guideline for this assay, i.e. TA1535, TA1537, TA98 and TA100. All of the compounds were mutagenic in one or more of the Salmonella tester strains, and all were positive in TA98 with S9. A considerable range of potency was seen in this assay. The chemicals were further examined in vitro for mammalian cell gene mutation at either the HGPRT or TK locus in a standard (CHO, V79 or L5178Y) cell system. Only one of the chemicals was mutagenic and only with S9. This chemical also showed the most potent response in the Salmonella assay. The second part of the study was an examination in vivo to see whether any genotoxic activity was expressed in the whole animal. The in vivo rat liver DNA repair (unscheduled DNA synthesis; UDS) assay was chosen as being the most likely to be sensitive to aromatic nitroazo compounds. All of the materials were negative when tested alongside a structurally related positive control. The chemicals were also examined in the mouse bone marrow micronucleus assay in order to provide a second in vivo assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis.

In this review we have evaluated the relationship between peroxisome proliferation and hepatocarcinogenesis. To do so, we identified all chemicals known to produce peroxisome proliferation and selected those for which there are data (on peroxisome proliferation and hepatocarcinogenesis) which meet certain criteria chosen to facilitate comparison of these phenomena. The summarised data and definition of the methodology used has been collected in appendices. These comparisons enabled us to evaluate the relationship between these phenomena using reliable data. As there is a good correlation between them, we further explored the mechanisms of action that have been proposed (direct genotoxic activity, production of hydrogen peroxide, cell proliferation and receptor activation). The relationship between these events in other species, including humans, was also reviewed and finally an overview of the assessment of human hazard is presented in section IX. Some of the first chemicals which were shown to produce peroxisome proliferation were also hepatocarcinogens whose carcinogenicity could not be readily explained by genotoxic activity. This raised the suggestion that the unusual phenomenon of peroxisome proliferation was intricately linked to the carcinogenic activity of these agents. Three questions have exercised the attention of regulatory, industrial and academic toxicology since then; are chemicals which elicit peroxisome proliferation in the liver actually a coherent class of chemical carcinogens?; does the early biological phenomenon of peroxisome proliferation have real predictive value for and mechanistic association with rodent carcinogenesis?; and what hazard/risk do these agents pose to humans that may be exposed to them? Whether peroxisome proliferators are indeed a discrete class of rodent carcinogens would appear to be the single, most important question. If so, then the assumptions and procedures relevant to human hazard and risk assessment should be applied to the class and should be essentially generic; if not, each chemical should be considered independently. Our critical analysis of the published data for over 70 agents which have been shown to possess intrinsic ability to induce peroxisome proliferation in the livers of rodents has led to the conclusion that there exists a strong correlation between peroxisome proliferation as n early effect in the liver and hepatocarcinogenicity in chronic exposure studies. An almost perfect correlation was observed between the induction of peroxisomes in the rodent liver and the eventual appearance of tumours following chronic exposure The few exceptions to this were largely explainable (section II).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗