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Biomedical subjects

M M Thompson

Publications and source records attributed to M M Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Provision of training in carotid surgery does not compromise patient safety.

BACKGROUND: Vascular surgeons perceive that carotid endarterectomy carries a higher risk of stroke if performed by a surgical trainee. Accordingly, some trainees consider that they receive a less than adequate training in carotid surgery before taking up a consultant position. The aim of this study was to establish whether the stroke rate was adversely affected if carotid endarterectomy was performed by a surgical trainee under consultant supervision. METHODS: This was a prospective study of 151 consecutive patients undergoing carotid endarterectomy between 1 January and 31 December 1996 using a standardized technique including intraoperative and postoperative transcranial Doppler monitoring and completion angioscopy. RESULTS: The overall mortality and/or disabling stroke rate was 0.7 per cent (one of 151 patients), whereas the mortality and/or any stroke rate was 1.3 per cent (two of 151). Surgical trainees performed 82 of 151 carotid endarterectomies, with a mortality rate of 1 per cent and a mortality and/or any stroke rate of 2 per cent. There was no significant difference in the incidence of retained thrombus or intimal flaps between trainees and consultants as detected by angioscopy. CONCLUSION: Vascular surgical trainees can receive a comprehensive training in carotid artery surgery without incurring an unacceptable increase in operative risk.

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PubMed1998

Marimastat inhibits neointimal thickening in a model of human vein graft stenosis.

BACKGROUND: There is now accumulating evidence that matrix metalloproteinases (MMPs), the physiological mediators of matrix deposition and degradation, play an important role in the development of intimal hyperplasia following arterial bypass. This study investigated the effect of marimastat, an orally active specific MMP inhibitor, on neointima formation in cultured human saphenous vein. METHODS: Segments of human saphenous vein obtained from ten patients undergoing arterial bypass surgery were cultured for 14 days in serum-supplemented RPMI medium (controls) or in control medium supplemented with marimastat at three different concentrations (treatment groups). Following culture, half of each segment was prepared for histological examination and MMPs were extracted from the other half for gelatin zymography. RESULTS: Marimastat inhibited neointimal thickening in a concentration-dependent manner; inhibition was significant at 10(-5) and 10(-6) mol/l (P=0.006). This observation was paralleled by a significant reduction in the levels of MMP-2 and MMP-9 in the tissues. CONCLUSION: Marimastat significantly reduced neointimal thickening in this laboratory model. MMP inhibitors may offer a potential therapeutic strategy in the prevention of intimal hyperplasia.

Cells, Cultured↗
PubMed1998

Changes in referral practice, workload, and operative mortality after establishment of an endovascular abdominal aortic aneurysm program.

PURPOSE: To determine the change in referral practice following establishment of an endovascular abdominal aortic aneurysm (AAA) program. METHODS: A prospective audit of all elective admissions for AAA was established in January 1994 at the initiation of an endovascular AAA program. A comparison was made between this cohort and the elective AAA repairs performed between 1981 and 1993. RESULTS: Since January 1994, 213 AAA patients (177 men; median age 73 years, range 54 to 88) have been referred for potential endovascular aneurysm repair. To date, 142 patients have undergone elective surgery (41 endovascular and 101 conventional). Between 1981 and 1993, 304 patients (255 men; median age 69 years, range 45 to 86) had elective aneurysm repair. Comparison of the two time periods has revealed significant increases in the number of tertiary referrals (41.8% versus 9.5%, p < 0.01), annual operations (50 versus 23, p < 0.05), and overall mortality (12% versus 6.7%, p < 0.05), the latter attended by a significant increase in cardiorespiratory comorbidity. CONCLUSIONS: The higher elective AAA mortality rate since the establishment of an endovascular program reflects a change in referral practice and may be directly attributable to an increase in the number of high-risk patients. An endovascular AAA program has clinical and financial implications for the hospital concerned.

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PubMed1998

Torsion and kinking of unsupported aortic endografts: treatment by endovascular intervention.

PURPOSE: To describe the management strategies used to deal with twisted aortic endografts. METHODS AND RESULTS: Two patients with successfully excluded aortic aneurysms developed symptoms referable to previously undetected twists in their endografts (one EndoVascular Technologies [EVT] and one customized aortomonoiliac device). The limb graft occlusion in the EVT graft was treated surgically with a femorofemoral bypass, but the aortomonoiliac endograft was salvaged with percutaneous implantation of a Wallstent. During another aortomonoiliac procedure, suboptimal flow through the endograft was traced to contortion of the endograft as it passed over an angulated proximal aneurysm neck. An X-large Palmaz stent was deployed to support the graft at this point. CONCLUSIONS: Unsupported aortic endografts may develop twists and kinks during deployment that can lead to low outflow and graft occlusion. Endovascular techniques are available to repair these defects postoperatively, although more precise intraoperative assessment tools may identify these problems so that they can be corrected at the initial intervention.

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PubMed1998

Endovascular repair of aortic aneurysms in the the presence of a horseshoe kidney.

PURPOSE: To report two cases of endovascular aortic aneurysm exclusion in patients with a horseshoe kidney. METHODS AND RESULTS: Two male patients, one with a known horseshoe kidney and history of multiple previous laparotomies, presented with abdominal aortic aneurysms of approximately 6-cm diameter. Each was treated with a tapered aortomonoiliac polytetrafluoroethylene graft secured proximally with a Palmaz balloon-expandable stent. The endograft was sutured distally to a Dacron femorofemoral crossover graft. An anomalous renal vessel was sacrificed in one case. The aneurysms were successfully excluded, and the patients recovered without sequelae. CONCLUSIONS: Endovascular repair should be considered as a treatment option in patients with aortic aneurysm in the presence of a horseshoe kidney, particularly if the renal vasculature can be wholly preserved.

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PubMed1997

Microembolization during endovascular and conventional aneurysm repair.

PURPOSE: Endovascular aneurysm repair has been advocated as a "minimally invasive" alternative to conventional aneurysm surgery. However, because of manipulation within the aneurysm sac, endovascular techniques may result in massive microembolization. METHODS: In this study lower limb microemboli were quantified in 29 patients undergoing conventional (11 straight and 7 bifurcated grafts) and endovascular aneurysm repair (8 aortoiliac, 1 straight, and 2 bifurcated grafts) by insonation of the superficial femoral artery with a 2 MHz Doppler probe. Emboli were detected as high-intensity, short-duration signals on the background Doppler trace. Differentiation of gaseous emboli from particulate emboli was achieved by calculation of the sample volume length (emboli velocity x duration = sample volume length) for each embolus (N = 4927). Previous experiments had determined that a sample volume length < 1.4 cm represented particulate embolization. RESULTS: The number of gaseous, particulate, and total emboli were significantly greater in the endovascular group compared with the conventional group (p < 0.05). CONCLUSIONS: These data demonstrate that peripheral microembolization is significantly higher during endovascular aneurysm repair than during conventional surgery. Methods to reduce embolization must be developed before endovascular aortic surgery is widely adopted.

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PubMed1997

Surgical management of 671 abdominal aortic aneurysms: a 13 year review from a single centre.

OBJECTIVE: To audit the results for abdominal aortic aneurysm (AAA) repair from a single centre over a 13 year period. DESIGN: Retrospective survey. SETTING: Vascular unit of a major teaching hospital. MATERIALS: Six hundred and seventy-one consecutive patients divided into two groups: group A (1981-87) and group B (1988-93). CHIEF OUTCOME MEASURES: Mortality rates, cause of death and major complications in patients undergoing elective, urgent and ruptured AAAs. RESULTS: Elective repair was performed in 313 (47%) patients, urgent repair in 80 (12%) and emergency repair for rupture in 278 (41%). A vascular surgeon performed the procedure in 94% of patients. The overall mortality was 21 patients in the elective group (6.7%), 13 in the urgent group (16%) and 148 in the ruptured group (53%). Mortality rates have not fallen during the study period but more patients in group B had ischaemic heart disease. Sixty patients (9%) required further operative procedures on 66 occasions: 24 elective cases (8%), 8 urgent cases (10%) and 28 ruptured cases (10%). There were 23 deaths in these 60 patients (38%) who underwent re-operation (5 elective, 2 urgent and 16 ruptured). Major postoperative complications included cardiac events in 212 (32%) patients, respiratory failure in 202 (30%) and renal failure in 90 (13%). Major causes of death included cardiac disease in 67 patients (37%), cardiac disease with coagulopathy in 22 (12%) and cardiac disease with respiratory failure in 16 (9%). Logistic regression analysis showed that in the elective group, cardiac or renal failure were significantly associated with death; and in the ruptured group cardiac, respiratory or renal failure were significantly associated with death. CONCLUSIONS: More high risk patients with ischaemic heart disease are undergoing AAA repair. Postoperative cardiac, respiratory or renal failure are significant causes of death in AAA patients.

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PubMed1997

Endothelial cell-conditioned medium downregulates smooth muscle contractile protein expression.

Smooth muscle cells (SMC) within atherosclerotic lesions proliferate and exhibit phenotypic modulation, but the contribution of vascular endothelium to this process is poorly understood. Our aim was to examine the effects of endothelial cell-conditioned medium (ECCM) on vascular SMC growth and differentiation. Rat aortic ECCM stimulated a ninefold increase in [3H]thymidine incorporation and downregulated smooth muscle-specific myosin heavy chain and alpha-actin synthesis in rat aortic SMC. These effects were not inhibited by antibodies to platelet-derived growth factor (PDGF)-BB or PDGF-AB or with a PDGF beta-receptor subunit. Treatment with PDGF-BB (at a concentration found in ECCM), PDGF-AA, basic fibroblast growth factor, endothelin-1, or transforming growth factor-beta did not reproduce these effects. The ECCM activities were sensitive to heat and trypsinization, were >30 kDa in molecular mass, and bound weakly to heparin-Sepharose. Our data indicate that cultured endothelial cells produce a factor(s) that downregulates contractile protein expression in SMC, which may contribute to SMC dedifferentiation and proliferation.

Actins↗
PubMed1997

Angiotensin II-induced stimulation of smooth muscle alpha-actin expression by serum response factor and the homeodomain transcription factor MHox.

The objective of the present study was to examine the molecular mechanisms whereby angiotensin II (Ang II) stimulates smooth muscle (SM) alpha-actin expression in rat aortic smooth muscle cells (SMCs). Nuclear run-on analysis and transfection studies indicated that the effects of Ang II on SM alpha-actin were mediated at least in part at the transcriptional level. Transfection of various rat SM alpha-actin promoter/chloramphenicol acetyltransferase (CAT) constructs into SMCs demonstrated that the first 155 bp of the SM alpha-actin promoter was sufficient to confer maximal Ang II responsiveness, conferring an approximately 4-fold increase in reporter activities in these SMCs compared with vehicle-treated SMCs. Mutation of either of two highly conserved CArG elements, designated A (-62) and B (-112), completely abolished Ang II-induced increases in reporter activity, whereas mutation of a homeodomain-like binding sequence at -145 (ATTA) reduced reporter activity by half. Results of EMSAs showed that nuclear extracts from Ang II-treated SMCs exhibited enhanced binding activity of serum response factor (SRF) to the CArG elements and of a homeodomain factor, MHox, to the ATTA element. Northern analyses showed that Ang II also stimulated marked increases in MHox mRNA levels. Western analyses demonstrated that Ang II-induced increases in SRF binding were not due to increased SRF protein expression. Recombinant MHox markedly enhanced binding activity of SRF in EMSAs. Finally, MHox overexpression transactivated a SM alpha-actin promoter/CAT reporter construct by approximately 3.5-fold in transient cotransfection studies. These results provide evidence for involvement of a homeodomain transcription factor, MHox, in Ang II-mediated stimulation of SM alpha-actin via a CArG/SRF-dependent mechanism.

Actins↗
PubMed1997

Ultrasound-based quantification of emboli during conventional and endovascular aneurysm repair.

PURPOSE: To differentiate and quantify the type and number of lower limb emboli occurring during endovascular aneurysm repair, as compared to conventional surgery. METHODS: Thirty-eight patients underwent elective infrarenal aneurysm repair using a conventional surgical approach in 18 and an endovascular procedure in 20. Emboli were detected using a Doppler ultrasound system with a 2-MHz transducer interrogating the mid superficial femoral artery. Lower limb emboli were differentiated as particulate or gaseous based on the physical distance traversed by the embolic signal. RESULTS: Significantly more particulate (median 108 versus 59, p = 0.015) and gaseous (134 versus 46, p = 0.008) emboli were detected during endovascular aneurysm repair as compared to conventional surgery. Clinically, no case of massive microembolization occurred in either group, but one patient in the conventional group required a femoral embolectomy, and three patients undergoing endovascular repair developed self-limiting trash feet postoperatively. In patients undergoing endovascular aortomonoiliac aneurysm repair, there was only a poor correlation between the number of particulate emboli and either procedural duration or operator experience. CONCLUSIONS: The apparent lack of a relationship between particulate embolization and operative time or technical experience suggests that manipulation of endoluminal devices within the aneurysm sac may not be the sole determinant of intraprocedural embolization. Other as yet undetermined factors may predict patients at high risk for massive embolization.

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PubMed1997

Improved respiratory function and analgesia control after endovascular AAA repair.

PURPOSE: Endovascular abdominal aortic aneurysm (AAA) repair has been proposed as a minimally invasive alternative to conventional surgery and may offer significant advantages in respiratory function and analgesic requirements due to the absence of an abdominal incision. METHODS: Respiratory function and analgesic requirements were quantified in 22 age-matched patients undergoing aneurysm repair under general anesthesia. Twelve patients underwent endovascular aneurysm repair, while 10 AAA patients had conventional surgery. One endovascular patient required conversion to conventional repair. RESULTS: The endovascular group required postoperative artificial ventilation for a shorter time (6 versus 21 hours, p < 0.05) and had lower PCA (patient-controlled analgesia) morphine consumption (41 versus 133 mg, p < 0.05) than the conventional group. The endovascular group also had significantly better forced expiratory volume and forced vital capacity at both 3 and 5 days when expressed as percentages of the preoperative values (p < 0.05). CONCLUSIONS: Endovascular AAA repair attenuates respiratory dysfunction associated with conventional surgery and reduces perioperative analgesia requirements.

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PubMed1997

Aortomonoiliac endovascular grafting: difficult solutions to difficult aneurysms.

PURPOSE: To describe a refined technique for aortomonoiliac endograft exclusion of abdominal aortic aneurysms (AAAs). METHODS: A tapered aortomonoiliac graft was prepared from an 8-mm thin-walled expanded polytetrafluoroethylene tube graft predilated proximally to 35 mm and tapered distally to 15 mm. The proximal graft was sutured to a 5-cm-long, predilated Palmaz stent, which was mounted on a 30-mm balloon and backloaded into a 21F packaging sheath. With the patient under general anesthesia and both common femoral arteries exposed, the endograft was anchored in the infrarenal aorta and subsequently passed into one iliac system, where it was anastomosed to the iliac or femoral vessels. The contralateral common iliac artery was occluded, and an extra-anatomic, femorofemoral, or iliofemoral bypass grafting was performed. RESULTS: Twenty of the 25 AAAs treated to date with this technique have been successful, with aneurysm exclusion achieved in 18 (2 minor distal endoleaks are scheduled for endovascular repair). The technical failures were analyzed, resulting in enhancements to the technique. Complications included 2 early (< 30 days) deaths, 1 case of minor embolization, 1 transient renal failure, 1 pulmonary embolus, and 1 wound infection. The only late complication was a graft infection localized to the groin. CONCLUSIONS: Aortomonoiliac endovascular aneurysm repair is effective in patients with AAAs involving the iliac arteries. Short-term results are acceptable, but long-term efficacy must be addressed before this procedure is widely adopted. Technical changes made in response to early learning curve problems have led to a safer, more reliable procedure.

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PubMed1997

Interactions of the kallikrein-kinin and renin-angiotensin systems in experimental diabetes.

The kallikrein-kinin system (KKS) has been postulated to play a role in modulation of hemodynamic function in diabetes and to contribute to the hemodynamic effects of angiotensin-converting enzyme inhibition (CEI). To further explore the KKS and its interactions with the renin-angiotensin system (RAS), studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic rats. In protocol 1, control and diabetic rats were studied before and after administration of one of two dissimilar B2 kinin receptor antagonists (BK2As), or vehicle. At a low dose (0.5 microg x kg-1 x min-1), the first generation antagonist D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin significantly reduced the glomerular filtration rate (GFR) and renal plasma flow rate in diabetic rats, despite variable effectiveness in blocking the hypotensive response to injected bradykinin. However, a similar hemodynamic effect occurred in nondiabetic rats, suggesting that the observed effect was not specific to diabetes. Higher doses (20 microg bolus, then 1 microg x kg-1 x min-1 infusion) did not affect hemodynamics in either group, perhaps because of partial agonist effect. The second BK2A tested was the newer compound, icatibant (Hoe 140; D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). Hoe 140 consistently blocked the vasodepressor action of injected bradykinin, but had no effect on systemic or renal hemodynamics in either control or diabetic rats. In protocol 2, control and diabetic rats were pretreated with the CEI ramipril for 1-2 weeks, after which renal function was studied before and after Hoe 140 (0.1 mg s.c. and i.v.) or vehicle. CEI lowered blood pressure in both groups. Hoe 140 did not affect renal function in control rats, but in diabetic rats pretreated with ramipril, it induced a modest but significant decline in GFR. Ramipril induced the predicted changes in the systemic and intrarenal RAS, while acute BK2A had no consistent effect on RAS parameters. These studies suggest that the endogenous KKS has only a minor role in modulation of renal hemodynamics in the euvolemic diabetic rat, in the absence of KKS stimulation by CEI. However, angiotensin-converting enzyme is also kininase II, which serves to increase endogenous kinin activity. The increased kinin activity resulting from CEI treatment may participate, to a modest degree, in hemodynamic regulation of the diabetic kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Lower limb amputation and grade of surgeon.

BACKGROUND: The aim of this study was to identify clinical and operative risk factors that might influence the rate of independent ambulation following major limb amputation. METHODS: Between 1989 and 1993, 172 patients had 193 lower limb amputations for peripheral vascular disease: 98 below-knee, 86 above-knee and nine through-knee. RESULTS: The overall revision rate was 13.5 per cent. Revision was significantly more frequent in those patients who had a previous vascular reconstruction. Only 26 per cent of patients were able to ambulate independently after rehabilitation and limb-fitting. Univariate risk factor analysis suggested that independent ambulation was not affected by age, mode of presentation, the presence of ischaemic heart disease, diabetes, smoking status, previous vascular reconstruction or the level of amputation. However, fewer patients whose amputation was performed by a junior trainee could walk with a prosthetic limb (P = 0.03). CONCLUSION: Patients considered suitable for walking training should have amputation performed by a senior trainee or consultant to optimize independent ambulation with a prosthetic limb.

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