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Biomedical subjects

B M Elliott

Publications and source records attributed to B M Elliott.

At least 19 recordsLinked to original sources

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

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

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

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

Limitations of subfascial ligation for refractory chronic venous stasis ulceration.

Eighteen subfascial ligations of deep venous perforators were performed on 17 patients with refractory venous stasis ulceration. Thirteen patients also required concomitant or subsequent split thickness skin grafting. Primary indications included: (1) recurrence of ulceration during adequate support therapy with failure to heal using conservative measures (10 cases--55%) and (2) failure to heal with support therapy alone (eight cases 45%). Five limbs had ulcers greater than 30 cm2 and two had giant ulcers (greater than 50 cm2). Most extremities had evidence of venous reflux by photoplethysmography or Doppler ultrasound (10 of 11) or chronic deep venous thrombosis by venography (six of seven). Mean hospital stay was 23 days +/- 17, range six to 68 days. Early complications, including incisional breakdown or partial skin graft loss, were common and occurred in 10 patients. With a mean follow-up interval of 28 months (range nine to 49 months), most limbs (N = 10) were judged cured, including both with giant ulcers, and three significantly improved. By life table analysis, 63% were free from significant ulcer recurrence at 42 months. Four limbs were not significantly improved following surgery. Most patients with refractory venous ulceration will benefit from subfascial ligation of deep venous perforators and skin grafting, although recurrent or persistent ulceration remains problematic for a significant number of patients.

Adult

Alternatives to Aroclor 1254-induced S9 in in vitro genotoxicity assays.

A working party was set up by the UK Environmental Mutagen Society to consider alternatives to Aroclor 1254 (Aroclor)-induced S9 in in vitro genotoxicity assays, with the aims of considering whether a replacement for Aroclor in its role in general screening assays could be readily identified. The working party concluded that there was sufficient support in the literature to justify the use of an appropriate phenobarbital/beta-naphthoflavone regime as an acceptable alternative to Aroclor.

Aroclors

Does postoperative surveillance with duplex scanning identify the failing distal bypass?

Duplex scanning used to determine graft flow velocities is an effective means of identifying lower extremity bypass grafts at risk for failure before they occlude. We implemented a graft surveillance protocol using duplex scanning and over a two-year interval evaluated fifty-four lower extremity bypasses utilizing graft flow velocities, ankle/brachial indices, and toe pressure measurements. Three patients were identified with grafts at risk for thrombosis. Of these patients, one had no evidence of arteriographic stenosis, one patient had clinical symptoms of reduced flow velocity measurements, and one's graft subsequently occluded during follow-up. Eight patients with graft flow velocities of greater than 45 cm/sec subsequently developed occlusion or were noted to have a severe associated stenosis. Six patients developed unheralded graft occlusion less than three months following determination of the graft flow velocity. Four of these patients (67%) had bypasses to the dorsalis pedis artery. Graft flow velocity measurements do not always predict an impending graft failure, and other factors may contribute to the sudden occlusion of patent distal bypasses, especially to the pedal arteries. Although the concept of hemodynamic monitoring to identify impending graft failure is an attractive one, more sensitive or refined measurements (especially to the pedal vessels), are required.

Arterial Occlusive Diseases

Dobutamine-201Tl imaging. Assessing cardiac risks associated with vascular surgery.

The prevalence of coronary artery disease among patients considered for vascular surgical reconstructive procedures is appreciable though often clinically not apparent. One hundred and twenty-six patients underwent dobutamine-201Tl imaging (DTI) in preparation for vascular reconstruction. Fifty-four patients (43%) had a normal study and underwent vascular reconstruction, with one postoperative myocardial ischemic event (1.8%). 30 patients (24%) had a fixed defect present on DTI, which was indicative of prior infarction. Twenty-eight of these 30 patients underwent vascular reconstruction, with three postoperative myocardial ischemic events (11%, p = NS). The presence of a fixed defect on DTI did not significantly increase the risk of ischemic events in patients undergoing vascular procedures. Forty-two (33%) patients had reperfusion of their defects on DTI, which was indicative of myocardial ischemia. Fifteen of these 42 (36%) were denied vascular reconstruction. Nine of the 42 (21%) had either coronary artery bypass graft surgery or coronary angioplasty performed before vascular reconstruction without any postoperative myocardial ischemic events. The remaining 18 patients with reversible ischemia identified by DTI underwent vascular reconstruction without preoperative cardiac intervention, and nine of these 18 (50%) suffered a postoperative myocardial ischemic event (p less than 0.0001). Although there was a difference in the incidence of ischemic events among patients undergoing peripheral vascular compared with aortic reconstruction (71% versus 36%), if there was reversible ischemia identified on DTI this did not reach statistical significance. DTI is a reliable screening test that allows for an accurate means of predicting cardiac risks associated with vascular reconstruction, as well as identifying patients that might benefit from further cardiac evaluation and preoperative intervention.

Aged

Venous thromboembolism: anticoagulation, lysis, or filter?

Experience and review of the literature suggest that when deep venous thrombosis does occur, standard anticoagulation with heparin followed by Coumadin is the mainstay of treatment for both deep venous thrombosis and pulmonary emboli. However, thrombolytic therapy with urokinase or streptokinase may benefit selected patients. Percutaneous caval interruption is the optimal technique to prevent pulmonary embolization, but should be reserved for patients who have contraindications to anticoagulation therapy or recurrent emboli despite adequate anticoagulation. Selected high risk patients may also be candidates for caval interruption.

Anticoagulants

The existence of an inactive form of transglutaminase within metastasising tumours.

Separation by anion exchange chromatography of detergent extracts from a poorly metastatic HSV-2-induced hamster fibrosarcoma, its highly metastatic variant and a highly metastatic rat fibrosarcoma indicated the presence of an inactive form of transglutaminase antigen, when eluent fractions were assayed for transglutaminase activity and antigen. This inactive antigenic transglutaminase was clearly separable from the particulate and cytosolic forms of the transglutaminase enzyme. Unlike tumours, its presence could not be demonstrated in extracts from normal rat liver. Measurement of activity levels during tumour growth indicated that the progression of the two highly metastatic tumours was accompanied by a decrease in cytosolic transglutaminase activity, whilst the activity of this enzyme form remained constant in the poorly metastatic tumour. Measurement of antigen levels indicated an inverse relationship between the level of inactive transglutaminase and the level of cytosolic transglutaminase activity, suggesting that the two forms are inter-related. Gel filtration indicated the molecular weight of the inactive form to be greater than both the particulate and cytosolic forms, and it was estimated to be 120,000. Partial proteolysis of the semi-purified inactive form, by either trypsin or thrombin, led to its activation and to the appearance of a transglutaminase similar in molecular weight and ionic mobility, both by anion-exchange chromatography and electrophoresis, to the cytosolic transglutaminase.

Animals

Immunological similarities between cytosolic and particulate tissue transglutaminase.

At the present time it is uncertain whether or not the cytosolic and particulate forms of tissue transglutaminase are distinct and discrete enzymes. In this study a number of physical and immunological similarities between the two forms are demonstrated, indicating that they share some common epitopes, although their native confirmations may differ.

Animals

Characterisation of the cellular substrates for transglutaminase in normal liver and hepatocellular carcinoma.

The transglutaminase-mediated incorporation of [14C]methylamine into tissue slices obtained from normal rat liver and diethylnitrosamine-induced hepatocellular carcinomas was used as a means of characterising the endogenous substrates of the transglutaminase enzymes present in these tissues. The amount of radiolabel incorporated was found to be similar in both tissues with the major radiolabelled protein identified as a high molecular weight polymer unable to traverse a 3.0% (w/v) acrylamide gel and with a molecular weight of at least 5 x 10(6) Da. Measurement of the crosslink, epsilon-(gamma-glutamyl)lysine, in the hepatocellular carcinoma and in normal liver indicated a 3-fold reduction in the levels found in tumour tissue when compared to normal liver. In contrast, the levels of covalently bound polyamines present in the hepatocellular carcinoma were found to be comparable or greater than those found in normal liver. Considering that there is a selective reduction (approx. 5-fold) in the activity of the cytosolic transglutaminase present in hepatocellular carcinomas with no change in the activity of the particulate enzyme (Hand et al. (1988) Biochim. Biophys. Acta 970, 137-145) these results suggests that the two enzymes may be differentially activated and that they may act on different substrates within the cell.

Animals

Preoperative evaluation of cardiac risk using dobutamine-thallium imaging in vascular surgery.

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery.

Aged

Aortic reconstruction in high-risk pulmonary patients.

Seventeen patients with clinical chronic obstructive pulmonary disease (COPD) who required aortic reconstruction underwent preoperative pulmonary function testing that categorized them as extremely high risk for pulmonary complications. Ten patients (Group 1) received perioperative steroids and seven patients (Group 2) received no perioperative adjunctive steroids. The mean forced expiratory volume (FEV 1) was 45% of the predicted value in Group 1 patients and 47% in Group 2 patients. The forced expiratory flow (25% to 75%) was severely restricted in both groups: 0.47 liters per second in Group 1 (16% +/- 6% predicted value) and 0.53 liters per second (20% +/- 7% predicted value) in Group 2 patients. Using a regimen consisting of preoperative pulmonary physiotherapy, optimization of theophylline levels, and early postoperative extubation with initiation of postoperative physiotherapy resulted in survival in all cases. There did not appear to be a clear advantage to the use of adjunctive perioperative steroids. The overall incidence of pulmonary complications was 22%. Four patients died during the follow-up interval. The remaining 13 patients were alive at a mean follow-up interval of 35 months. Using a number of adjunctive techniques, successful aortic reconstruction can be accomplished in many patients with severe COPD, and the majority will survive for extended periods after operation despite their impaired pulmonary function.

Aorta, Abdominal

Nifedipine-induced hypotension and mesenteric ischemia.

We have presented a case in which nifedipine-induced hypotension in a patient receiving beta blocker and nitrate therapy precipitated mesenteric angina, leading to emergency exploratory celiotomy. Although paradoxic angina is an unusual complication of this antianginal therapy, it should be considered in any patient who has acute abdominal pain and hypotension while receiving this therapeutic regimen.

Adrenergic beta-Antagonists

Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis.

Transglutaminase (EC 2.3.2.13) activity in chemically induced rat hepatocellular carcinomas was reduced by some 65% when compared to normal rat livers. The majority of the remaining activity (approx. 85%) was found in the particulate fraction. The use of non-ionic detergent to extract the transglutaminase activity present in both normal and tumour tissue followed by its separation on a Mono-Q column revealed two distinct peaks of activity. These peaks of activity were equivalent to those previously identified as a membrane-bound transglutaminase and the more characteristic cytosolic or tissue transglutaminase. The ratio of the activity of the cytosolic enzyme to that of the membrane-bound enzyme in normal liver was calculated as 5:1. In hepatocellular carcinomas, this ratio was reduced to 0.4:1. No significant change in the activity of the membrane-bound enzyme was detectable in tumour tissue. Comparison of the cytosolic enzyme found in hepatocellular carcinomas with that found in normal liver indicated no change in its molecular weight, Km,app for putrescine incorporation into N,N'-dimethylcasein and sensitivity to activation by Ca2+. These observations suggest that the reduction in transglutaminase activity observed in the hepatocellular carcinoma is due to a selective reduction in the expression of the cytosolic transglutaminase.

Animals