Search PubMed⌕ Search

Biomedical subjects

B R Hopkinson

Publications and source records attributed to B R Hopkinson.

At least 91 records · Page 5Linked to original sources

Detection and characterization of arterial thromboses using a platelet-specific monoclonal antibody (P256 Fab').

Arteriography does not reliably distinguish between acute and chronic arterial occlusions. Seventeen patients with acute lower limb ischaemia were investigated by arteriography and by imaging with a platelet-specific monoclonal antibody (P256 Fab'); 20 MBq 111In-labelled P256 Fab' was administered intravenously and patients were imaged at intervals of between 20 min and 24 h. Thirteen patients were subsequently treated with intra-arterial thrombolysis. In six the images showed foci of increased uptake of 111In-labelled P256 Fab' and the corresponding arterial segment was recanalized. Patency to 30 days was maintained in four cases. Seven patients had negative scans, only four of whom achieved lysis, and two of these suffered early rethrombosis. The remaining four patients were excluded from thrombolysis by the arteriographic appearances. 111In-labelled P256 Fab' imaging can identify sites of acute arterial thrombosis and may have clinical applications in the management of peripheral vascular disease. Further studies are required to test whether the technique has a role to play in patient selection for thrombolysis.

Antibodies, Monoclonal↗

Tissue plasminogen activator in peripheral arterial thrombolysis.

Thirty acute peripheral arterial thromboses in 28 patients were treated with local low-dose intra-arterial recombinant tissue plasminogen activator (t-PA). All patients received 0.5 mg h-1 t-PA and 15 also received 250 units h-1 of intra-arterial heparin. Overall limb salvage at 30 days was 83 per cent (25 out of 30 limbs). Mean(s.d.) ankle/brachial index was increased by 0.53(0.26) and there was no significant difference between the group receiving t-PA alone and that receiving t-PA and heparin. No strokes or major haemorrhages occurred but there were four (13 per cent) minor haematomas associated with the catheter entry site. There were four (13 per cent) deaths from myocardial infarction occurring between 5 and 21 days after treatment. Rethrombosis occurred in four cases (13 per cent). In two patients following t-PA alone, rethrombosis occurred after 2 and 11 days. Limb salvage was achieved with a successful repeat thrombolysis and a femoropopliteal graft respectively. Rethrombosis after t-PA and heparin occurred after 30 days in two patients due to poor run-off and extensive proximal atheromatous disease respectively. t-PA is a safe, effective thrombolytic agent when given as a low-dose intra-arterial infusion. The addition of low-dose heparin does not produce any significant benefit.

Acute Disease↗

A simple technique for thromboembolectomy of the upper limb.

Brachial emboli account for only 18% of arterial emboli and present as an uncommon emergency to surgeons. We have examined the route taken and probable outcome of arterial embolectomy of the upper limb in 31 cadaveric limbs using standard and Coude tipped embolectomy catheters. Using a standard embolectomy catheter, the larger of the two upper limb arteries was cannulated in only 42% of our series. However, using a 30 degree Coude tipped catheter, both radial and ulnar arteries could be cannulated in 87% of limbs, ensuring a more complete embolectomy without the need formally to expose the brachial artery bifurcation.

Aged↗

Acute critical ischaemia of the limb: a prospective evaluation.

A total of 119 patients with acute peripheral arterial ischaemia were studied prospectively to validate the definition of acute critical ischaemia suggested by the working party of the International Vascular Symposium. The majority of the patients had primary treatment using thrombolytic therapy. Overall limb salvage after 30 days was achieved in 56% of the patients, 19% required amputations and 25% died. Comparisons of the outcome in patients with or without a distal neurosensory deficit (limb salvage 30% vs. 72%, P = 0.0001) and those with absent or audible Doppler ankle blood flow (limb salvage 37% vs. 78%, P = 0.0001) confirmed that the severity of the initial ischaemia was a significant indicator of prognosis. The definition of acute critical ischaemia as assessed by objective measurement of Doppler pressures has been validated and can be used to divide patients into groups with critical and sub-critical ischaemia with different prognoses.

Acute Disease↗

111In platelet deposition following peripheral arterial thrombolysis.

Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients.

Blood Platelets↗

Risk factors in patients with ischaemic rest pain of the lower limbs.

One hundred and three consecutive out-patients with ischaemic rest pain were studied. There were 77 men and 26 women with a mean (s.d.) age of 71 (10) years. Thirty-six (35.0%) patients had rest pain alone, 41 (39.8%) in association with an ischaemic ulcer and 26 (25.2%) with digital gangrene. A significantly increased risk of amputation was seen in those patients with an elevated serum cholesterol (greater than 5.2 mmol/l; P = 0.01), white blood cell count of greater than 10 x 10(9)/l (P = 0.05), fibrinogen greater than 4g/l (P = 0.04), and in women with elevated triglyceride levels (greater than 1.8 mmol/l; P less than 0.03). An increased risk of death for all patients was also associated with elevated triglyceride levels (P = 0.03). Few of the women smoked (P less than 0.0004), but they were more likely to have suffered a stroke (P = 0.01). They also had a significantly increased cholesterol level (P = 0.03) and tended to have a higher mortality rate than the men (P = 0.08). Surprisingly, smokers did not have a significantly higher amputation or death rate than non-smokers. Elevated plasma viscosity, packed cell volume, platelet count, haemoglobin and creatinine levels were not independent risk factors for any group. At 30 days after presentation the limb salvage rate was 73% (75/103), amputation was required in 15 (14.6%) cases and 13 (12.6%) patients died. Patients with ischaemic rest pain constitute a heterogeneous group with multiple diseases and risk factors. Early identification and treatment of risk factors may help to improve limb salvage and the mortality rate in this condition.

Aged↗

Technique of in situ saphenous vein arterial bypass: can the valves help to locate the major venous tributaries?

Ten cadaveric great saphenous vein systems have been dissected to assess the relationship between the valves and the termination of venous tributaries. Such tributaries were classified on the basis of size, competence and course, and the percentage of each of four classes terminating within 1 cm of each valve site has been assessed. Above the knee, valves were more numerous, closer together, and two-thirds of competent tributaries terminated within 1 cm of them, this relationship being weaker for other classes of tributary. Below the knee, less than 50% of any class of tributary was related to valves. Reference to the position of valves is not recommended as the sole method of locating potential arteriovenous fistulae.

Cadaver↗

Fibrinolytic profiles in local low-dose thrombolysis with streptokinase and recombinant tissue plasminogen activator.

Fibrinolytic parameters have been monitored in 44 patients undergoing local low-dose intra-arterial thrombolysis for acute peripheral arterial ischaemia. Streptokinase (Sk), at a dose of 5,000 units/hr with 250 units/hr heparin, was used in 23 patients and recombinant tissue plasminogen activator (r-tPA) at a dose of 0.5 mg/hr was used in 21 patients. Successful lysis was seen in 18 (86%) patients following r-tPA and in 15 (65%) patients following streptokinase. There were 4 minor haematomas in each group usually at the catheter entry site. Both agents produced a systemic effect, which was still seen 12 hours post-infusion. However, that produced by r-tPA was delayed and significantly reduced compared to that produced by Sk. These results confirm the relative fibrin specificity of r-tPA. When used as a continuous low-dose intra-arterial infusion, r-tPA offers a significantly lower, potentially safer, systemic effect than conventional therapy with streptokinase.

Fibrin Fibrinogen Degradation Products↗

111In-labelled leucocyte imaging in vascular graft infection.

Twelve patients with a clinical diagnosis of possible vascular graft infection have been studied over the last 3 years. All patients had their leucocytes labelled with indium-111 and gamma-camera imaging after 24 and 48 h. Subsequent management was according to established surgical techniques. Eight patients proved to have vascular graft infection and indium uptake was seen along the length of the graft in six. Two patients with open wound infections and synthetic grafts had localized uptake only on leucocyte scanning. Four patients, all of whom had negative scans were not thought to have infected grafts after further investigation using digital subtraction angiography and computed tomography scanning. These patients have been followed up for a median period of 19 months (range 5-25 months) and have remained symptom free. Initial experience with 111In-labelled leucocyte scanning has been encouraging, both in diagnosis and in planning the management of patients with graft infections.

Bacterial Infections↗

Delayed recovery of hand grip strength predicts postoperative morbidity following major vascular surgery.

Forearm muscle dynamometry was performed in the non-dominant arm in 61 patients undergoing major abdominal and limb vascular surgery, before operation and then 1, 3, 5, and 7 days after surgery. Six patients died in the postoperative period and seven patients developed major postoperative complications (bronchopneumonia, two; wound infection, four; myocardial infarction, one). The preoperative grip strength, measured in kilograms, of the patients who died after major vascular surgery was not significantly lower than that of patients who had an uncomplicated postoperative course. Of the 55 surviving patients, seven developed complications after surgery. These patients had significantly reduced grip strength, expressed as a percentage of the individual preoperative value (P less than 0.05), from the first to the seventh postoperative day when compared with patients without complications. The delayed recovery of grip strength preceded the clinical manifestation of complications. These data suggest that delayed recovery of voluntary muscle performance may be used to detect patients developing postoperative complications and so allow their early treatment.

Adult↗

Acute lower limb arterial ischaemia: a role for continuous oxygen inhalation.

Simultaneous readings of transcutaneous partial pressure of oxygen (Ptc,O2) were obtained from the left anterior chest wall, from 10 cm distal to the medial aspect of the knee joint, and from the first dorsal webspace in 16 patients with acute peripheral arterial ischaemia of the leg. Oxygen was administered at concentrations of 24, 40, 60 and 100 per cent. Mean (s.d.) initial chest Ptc,O2 (53(17)mmHg) was significantly higher than that of the medial lower limb site (37(17)mmHg). After inhalation of 24 per cent oxygen, a statistically significant (P less than 0.025) increase in chest Ptc,O2 was achieved (63(20)mmHg), but the increase in Ptc,O2 (43(19)mmHg) at the medial lower limb site was not statistically significant. Inhalation of 40 per cent oxygen resulted in significant increases at both sites (chest: 83(23)mmHg, P less than 0.01; limb: 53(26)mmHg, P less than 0.05). Ptc,O2 in the limb at this concentration of inhaled oxygen was equal to the initial chest level. Increasing the oxygen concentration to 60 per cent and then to 100 per cent produced further significant (P less than 0.001) increases in Ptc,O2 at both sites. The use of continuous oxygen inhalation during acute ischaemia may improve tissue nutrition before, during and after definitive treatment.

Acute Disease↗

Differential effects of low-dose tissue plasminogen activator and streptokinase on platelet aggregation.

Despite increasing success with low-dose intra-arterial thrombolysis, early rethrombosis still occurs. Platelet aggregation is thought to play a major part in this process. We have therefore investigated the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase on platelet function at doses currently used for peripheral arterial thrombolysis. Platelet-rich plasma was stirred at 37 degrees C, with either streptokinase (100, 300 or 1000 units ml-1) or rt-PA (10 (T10), 30 (T30) and 100 (T100) mg l-1), with immediate addition of an agonist for platelet aggregation (thrombin, collagen, adenosine diphosphate (ADP) or adrenaline) at a predetermined threshold dose. Significant inhibition of collagen-induced and adrenaline-induced platelet aggregation was produced with rt-PA at all doses used (P less than 0.05). With adrenaline as the agonist, T100 produced disaggregation to a mean (s.d.) level of 26 per cent. Thrombin-stimulated platelet aggregation was significantly reduced by T100 (P less than 0.001) and T30 (P less than 0.01) only, disaggregation being dose-dependent and complete with T100. Using ADP as the agonist, T100 produced a significant reduction in maximum platelet aggregation (P less than 0.01), and disaggregation was achieved to a mean (s.d.) level of 48(13) per cent. Streptokinase did not produce any significant changes in any parameter of aggregation.

Adenosine Diphosphate↗

Local low dose intra-arterial thrombolytic therapy: the risk of stroke or major haemorrhage.

The use of local low dose thrombolysis is gradually increasing. Most experience is with streptokinase, although newer agents such as recombinant tissue plasminogen activator (rTPA) may offer more effective lysis with reduced complications. We have reviewed the experience documented in 19 prospective series published between 1974 and 1988 in an attempt to define the incidence of stroke, major haemorrhage and minor haemorrhage. The overall risk of stroke was 1.0 per cent of patients (14 cases). Major haemorrhage occurred in 5.1 per cent of patients (71 cases) and minor haemorrhage occurred in 14.8 per cent (92 out of 620 cases). There was little difference between the two thrombolytic agents, although the experience with lower doses of rTPA suggests it may offer a reduced risk of haemorrhagic complications. It is essential that all studies concerning thrombolysis should give their exclusion and inclusion criteria in full to allow an accurate appraisal of haemorrhagic complications, with the hope of improved patient selection and reduced morbidity in the future.

Cerebrovascular Disorders↗

A bacteriological survey of amputation wound sepsis.

A retrospective survey of 100 lower limb amputations performed for ischaemia were analysed to assess the influence of preoperative bacterial isolates and the use of prophylactic antibiotics on wound sepsis. Forty-eight per cent had previously undergone a vascular procedure to attempt limb salvage and 17% were diabetics. Benzylpenicillin was given preoperatively and continued for 5 days; diabetics received metronidazole in addition. A total of 51 isolates were obtained from 30 patients preoperatively; Staphylococcus aureus and Enterobacteriaceae each accounted for over 25%. Postoperatively, 74 isolates (20 multiple) were obtained with an overall sepsis rate of 40%. Those patients with a positive preoperative culture were significantly more likely to develop wound sepsis. There was no significant difference in wound sepsis rates for diabetics. In view of the range of organisms causing postoperative infection, we recommend prophylaxis with a broad spectrum antibiotic for amputations.

Aged↗

Acute peripheral arterial ischemia: a prospective evaluation of differential management with surgery or thrombolysis.

In this three year prospective study of 177 patients with acute peripheral arterial ischemia those subjects with acute iliofemoral emboli or ischemia with a neurosensory deficit had urgent operations. The remainder included patients less likely to have limb salvage after surgery and who therefore were treated with thrombolytic therapy. This was done in three open studies of intravenous, acylated, plasminogen-streptokinase activator complex, low dose intraarterial streptokinase and intraarterial tissue-plasminogen activator (t-PA). The overall outcome after 30 days of thrombolytic therapy was limb salvage (55%), amputation (15%), and death (30%). The severity of the presenting ischemia was the most important prognostic indicator. In patients with a neurosensory deficit, limb salvage after either embolectomy or surgical reconstruction (59%) was more likely than after thrombolysis (31%). In patients without a neurosensory deficit, limb salvage after thrombolysis (68%) was better, though not significantly, than after surgery (53%). Local intraarterial thrombolysis with either streptokinase or t-PA produced an encouraging 66% limb salvage in 59 cases. In management of acute peripheral arterial occlusions an approach based on the severity of ischemia is optimal, with urgent surgery for patients with a neurosensory deficit and intraarterial thrombolytic therapy reserved as an alternative in selected cases with stable ischemia.

Acute Disease↗

Screening for clinically unsuspected abdominal aortic aneurysms in patients with peripheral vascular disease.

In patients with abdominal aortic aneurysms, most fatalities occur from rupture before the patient can be brought to hospital. Even when seen in hospital the mortality is still approximately 50% in contrast to elective repair which has a substantially reduced mortality of less than 5%. In order to reduce the number of patients dying from rupture, they must be diagnosed early to allow elective intervention, hence there has been considerable renewed interest in screening for abdominal aortic aneurysms. We have studied a consecutive series of 104 patients with either claudication or ischaemic rest pain in the lower limbs to determine the incidence of aortic aneurysms in this type of patient.

Aged↗