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Biomedical subjects

M M Thompson

Publications and source records attributed to M M Thompson.

At least 73 records · Page 4Linked to original sources

Arteriography in chronic renal failure: a case for carbon dioxide.

PURPOSE: The aim of this study was to assess the utilisation of carbon dioxide arteriography, performed with a simple injection system, as the imaging technique of choice in patients with chronic renal failure. METHODS: Patients with chronic renal impairment who required arterial imaging or intervention were recruited for carbon dioxide angiography. Demographic data were prospectively recorded and pre- and post-arteriogram renal function was quantified. Radiographic images were graded by an independent radiologist. RESULTS: Twenty-eight patients underwent renal or aorto-femoral studies with only one failure. There were no cases of contrast-induced nephropathy. Twenty-two of the films (79%) were graded as excellent or good, four as acceptable and two were considered to be poor (non-diagnostic). CONCLUSIONS: This study has demonstrated that carbon dioxide angiography is a safe and clinically effective procedure in patients with chronic renal failure.

Aged↗

Physiological comparison of open and endovascular aneurysm repair.

BACKGROUND: This prospective study compared morbidity and mortality rates following conventional and endovascular abdominal aortic aneurysm (AAA) repair using a physiological scoring system. METHODS: Between December 1994 and November 1997, 104 elective open aneurysm repairs and 49 endovascular aneurysm repairs were performed. These patient cohorts were compared using the Portsmouth predictor equation (P-POSSUM) scoring system. Data collected prospectively from patient notes were used to obtain physiological and operative severity scores which were analysed to compare expected and observed mortality and morbidity rates. RESULTS: There were three deaths (6 per cent) in the endovascular AAA repair group and 17 (16 per cent) in the conventional aneurysm repair group, whereas the P-POSSUM formulae predicted mortality rates of 8 and 19 per cent respectively. Although the mean physiological scores were similar for both groups (endovascular 20.8 versus conventional 20.1), the operative severity score was significantly greater in the conventional group (26.3 versus 19.7; P < 0.001). CONCLUSION: In this study open aortic aneurysm repair had a higher operative severity than endovascular repair, which was reflected in the increased mortality rate.

Aged↗

Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease.

BACKGROUND: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. METHODS: Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10(-5), 10(-6) and 10(-7) mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller's elastin and van Gieson's stain. RESULTS: Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10(-6) and 10(-5) mol/l; this was significant at the latter concentration (P = 0.007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10(-5) mol/l (P < 0.01). CONCLUSION: Marimastat significantly inhibited elastin degradation and active MMP-2 production within aortic organ cultures.

Animals↗

A prospective randomized trial evaluating the haemodynamic role of incompetent calf perforating veins.

AIM: This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. METHODS: Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. RESULTS: Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. CONCLUSIONS: At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

Adult↗

Hypertension and renal injury in experimental polycystic kidney disease.

UNLABELLED: Hypertension and renal injury in experimental polycystic kidney disease. BACKGROUND: Hypertension accelerates renal failure in autosomal dominant polycystic kidney disease (ADPKD), and evidence suggests a role for the renin-angiotensin system (RAS) in the functional and structural changes. To explore the hypothesis that RAS adaptations contribute to disease progression, we examined RAS activity and the long-term consequences of antihypertensive drugs, which suppress (enalapril) or stimulate (hydralazine) the RAS, in experimental polycystic kidney disease. METHODS: Studies were conducted in male heterozygous cystic Han:SPRD rats (Cy/+) and in unaffected littermates (controls). In protocol 1, either angiotensin II (Ang II), enalaprilat, or saline vehicle was acutely infused into cystic and control rats, which were aged 10 to 12 weeks. The mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured at baseline and after an infusion of test substances. In protocol 2, cystic rats received chronic therapy with either enalapril, hydralazine, or no therapy for 10 to 12 weeks of age and then underwent renal function and RAS studies. In protocol 3, similar cohorts were followed for 40 weeks to assess the effects of therapy on blood pressure, proteinuria, serum creatinine, RAS parameters, and renal morphology. RESULTS: In protocol 1, cystic rats had massive kidneys, slightly elevated blood pressure, and profound renal vasoconstriction and reduced GFR. Ang II induced similar changes in MAP and renal function in control and cystic rats. Enalaprilat induced little effect on MAP but more striking increases in GFR and RPF in cystic rats. In protocol 2, at 10 weeks of age, enalapril was superior in preserving renal function, but neither drug limited the expansion of the tubulointerstitium. In protocol 3, at 40 weeks of age, both drugs ameliorated the increase in serum creatinine, although only enalapril reduced proteinuria and kidney size. CONCLUSIONS: In polycystic rats, acute RAS suppression markedly ameliorates renal dysfunction. However, although chronic enalapril and hydralazine protect against the loss of renal function, only enalapril limits renal growth and proteinuria, and neither significantly limits tubulointerstitial fibrosis. The long-term studies give clear support to the importance of blood pressure control, per se, but only partial support to the importance of the particular agent used. As in clinical studies, angiotensin-converting enzyme inhibition may be less beneficial in ADPKD than in renal diseases characterized by predominant glomerular injury.

Angiotensin II↗

Cardiovascular and catecholamine responses during endovascular and conventional abdominal aortic aneurysm repair.

OBJECTIVES: To compare changes in plasma catecholamines, acid-base status and cardiovascular dynamics in patients undergoing endovascular or conventional infrarenal abdominal aortic aneurysm (AAA) repair under standard general anaesthesia. DESIGN: Prospective cohort study. MATERIALS: 30 patients scheduled for elective infrarenal AAA repair. METHODS: Plasma epinephrine and norepinephrine concentrations, acid-base status and cardiovascular measurement were compared before surgery, and 5 min after aortic clamping and clamp release (conventional group) or occlusion and release (endovascular group) in patients undergoing endovascular (n = 15) or conventional AAA repair (n = 15). RESULTS: Arterial pH (p < 0.005) and base deficit (p < 0.05) increased, and plasma bicarbonate decreased (p < 0.005) during aortic cross-clamping in the conventional group. pH decreased further (p < 0.005), and base deficit and pCO2 increased (both p < 0.005) after clamp release. These changes were significantly greater than during endovascular repair, in whom within-group changes were not statistically significant. Values were similar in the two groups 30 min after reperfusion. Plasma epinephrine concentrations increased during conventional surgery (p < 0.05) and were greater than in the endovascular group (p < 0.05). Plasma norepinephrine concentrations increased during surgery in both groups but the changes were not statistically significant. CONCLUSIONS: Plasma catecholamine concentrations, changes in cardiovascular variables and acid-base status were increased during conventional compared with endovascular AAA repair.

Acid-Base Equilibrium↗

Production and inhibition of the gelatinolytic matrix metalloproteinases in a human model of vein graft stenosis.

OBJECTIVES: human vein graft stenoses are caused by intimal hyperplasia, a process which is characterised by extensive degradation and accumulation of extracellular matrix. This study investigated the role of the matrix metalloproteinases (MMPs) - the principal physiological mediators of extracellular matrix degradation - in the development of intimal hyperplasia in cultured human long saphenous vein. DESIGN: experimental study. MATERIALS AND METHODS: paired venous segments with the endothelium intact or denuded were cultured in standard conditions for 14 days. At the termination of culture, MMPs were extracted from one half of the tissue, whilst the remainder of the vein was prepared for histological examination. RESULTS: stereologic analysis revealed that the endothelium intact veins developed a significantly thicker neointima when compared to the denuded venous segments (20 micron v. 0 micron, p=0.006). Quantification of MMPs by substrate gel enzymography demonstrated that the development of a neointima was associated with increased production of the gelatinolytic MMP-9 (p=0. 03) in intact veins. Immunocytochemistry showed that the MMP-9 localised to the internal elastic lumina, which suggested a role in facilitating smooth-muscle-cell migration into the intima. The role of MMPs-2 and -9 in intimal hyperplasia was further investigated by culturing intact venous segments with a therapeutic concentration of doxycycline--a potent MMP inhibitor. These experiments demonstrated that a therapeutic dose of doxycycline significantly reduced neointimal thickness (control 21 micron, doxycycline 10 mg/l-5.5 micron), in conjunction with a significant reduction in the production of MMP-9. CONCLUSIONS: these data suggest that elevated levels of MMPs may play a significant role in the development of human intimal hyperplasia and that inhibition of these enzymes may offer a potential therapeutic strategy for the prevention of hyperplastic lesions.

Anti-Bacterial Agents↗

Nocturnal hypoxaemia and respiratory function after endovascular and conventional abdominal aortic aneurysm repair.

Respiratory function, assessed by pre- and postoperative spirometry, and overnight pulse oximetry recordings, was compared prospectively in patients undergoing infrarenal abdominal aortic aneurysm repair by endovascular or conventional surgery. Episodic hypoxaemia was common in both groups before operation and up to the fifth night after operation. The frequency and severity of hypoxaemia were greater in the conventional group (P < 0.05). FEV1 and FVC decreased significantly on the third and fifth days after operation in both groups (P < 0.05); decreases in FVC were greater in patients undergoing conventional surgery. On the fifth day after operation, FVC had recovered to 86% and 64% of preoperative values in the endovascular and conventional groups, respectively (P < 0.05). Duration of surgery was greater (P < 0.05) and duration of postoperative artificial ventilation significantly less (P < 0.05) after endovascular repair. Postoperative PCA morphine consumption and duration of use were significantly greater (P < 0.05) in patients undergoing conventional abdominal aortic aneurysm surgery.

Aged↗

Quality control during endovascular aneurysm repair: monitoring aneurysmal sac pressure and superficial femoral artery flow velocity.

PURPOSE: To use intraoperative aneurysmal sac pressure measurement and flow monitoring of the superficial femoral artery (SFA) to ensure complete exclusion of the aneurysm from the circulation. METHODS: A 5F catheter was positioned in the aneurysmal sac of 15 consecutive patients undergoing endovascular aortomonoiliac aneurysm repair between February and September 1997. The catheter was connected to an external pressure transducer allowing pressure monitoring throughout the operation and for 24 hours postprocedurally. Flow velocity was monitored in the contralateral SFA by insonation with a 2-MHz Doppler ultrasound probe. RESULTS: No technical defect was observed in the deployment of 10 endografts, which demonstrated marked reduction in sac pressure and good flow in the lower limb. The mean aneurysm pressure dropped from 123 to 57 mmHg after graft insertion. In 5 cases, monitoring detected problems during the endograft procedure. In 3, incomplete stent deployment was detected by a failure of sac pressure to fall following stent inflation and by the presence of flow in the contralateral femoral artery. In the other 2 cases, a distal endoleak was detected by direct injection of contrast into the sac. CONCLUSIONS: Measuring aneurysm pressure in combination with SFA Doppler flow monitoring can detect complications of endovascular aneurysm repair.

Aged↗

Acute and chronic renal effects of recombinant human TGF-beta2 in the rat.

The expression of transforming growth factor-beta (TGF-beta) correlates with the incidence of renal glomerular and interstitial injury, however, nothing is known of the effect of these proteins on renal hemodynamics. This study examines the renal hemodynamic and morphologic effects of recombinant human TGF-beta2 in normal male Sprague Dawley rats. Acute infusion of TGF-beta (1.2 microg/kg per min) induced no hemodynamic changes, except for a modest though significant fall in mean arterial pressure. Administering TGF-beta2 at varying doses (20, 100, and 400 microg/kg) for 9 wk caused modest increases in systolic BP and proteinuria and minimal tubular interstitial fibrosis, however, renal hemodynamic end points were not significantly altered. TGF-beta2 (800 microg/kg) was also administered to volume-depleted rats for 7 consecutive days. In contrast to the findings in volume-replete animals, administration of TGF-beta2 to volume-depleted rats caused a marked reduction in GFR and medullary blood flow. Histologic fibrosis of the medullary vasa recta and cortical interstitium was seen, but glomeruli were unaffected. Thus, acute and short-term chronic TGF-beta2 administration did not induce major renal changes in the volume-replete state, however, TGF-beta2 combined with volume depletion caused medullary hypoperfusion and reduced GFR.

Analysis of Variance↗

Thromboembolic complications during endovascular aneurysm repair.

Thromboembolic complications are relatively uncommon after conventional aneurysm surgery but have been reported in many early series of endovascular aneurysm repair. This article reviews the clinical evidence for embolization during endoluminal procedures and presents an ultrasound-based method to detect lower limb embolization during aneurysm repair. The results of a comparative clinical trial are presented that demonstrated a higher incidence of particulate embolization during endovascular as compared with conventional aneurysm surgery. The implications of this finding for clinical practice are discussed.

Aortic Aneurysm, Abdominal↗

Is endoluminal abdominal aortic aneurysm repair using an aortoaortic (tube) device a durable procedure?

Endoluminal repair of abdominal aortic aneurysm (AAA) is being adopted as a less invasive alternative to conventional open repair in many centers worldwide. Although the initial results are encouraging, the long-term durability of this procedure remains unknown. Endoluminal AAA repair in 29 patients using three different devices (EVT tube Endograft(R), aortouniiliac device, and Stentortrade mark bifurcated system) is described. Overall, 24 procedures (83%) were completed successfully. Complications included two deaths due to microembolization, five early conversions, two chest infections, three patients with buttock claudication, and three patients with trashed foot. Perigraft leaks were detected in four patients (three proximal, one distal) treated with the EVT tube Endograft. Continued aneurysm expansion was observed in three of the patients. One of the leaks was discovered at the 1-year follow-up. In this patient the aneurysmal process was not retarded by endoluminal repair. The findings in this patient may have implications for the durability of this technique. Therefore, careful long-term evaluation of this procedure is recommended prior to its widespread use.

Aged↗

Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease.

PURPOSE: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta, which provide a potential therapeutic target for pharmacologic agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of doxycycline--an MMP inhibitor--to reduce matrix degradation was assessed in a previously described model of aneurysmal disease that used a brief pulse of elastase to induce MMP production and elastin degradation in arterial organ cultures. METHODS: Porcine aortic segments (n = 8) were preincubated in exogenous pancreatic elastase for 24 hours before culture in standard conditions for 13 days with both 1 and 10 mg/L doxycycline. Control segments were cultured both without doxycycline and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereologic analysis of sections stained with Miller's elastin and van Gieson's stain. RESULTS: Stereologic analysis demonstrated a significant preservation of elastin in aorta treated with doxycycline 10 mg/L (p < 0.001) and demonstrated that this preservation was accompanied by a significant reduction in MMP-9 activity (p < 0.02). Immunoblotting for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) showed no decreased production in the doxycycline-treated groups. CONCLUSIONS: Therapeutic ranges of doxycycline significantly inhibited elastin degradation and MMP-9 production within aortic organ cultures. These data suggest that doxycycline may have a potential application in reducing the growth rates of small abdominal aortic aneurysms.

Animals↗

Amlodipine potentiates metalloproteinase activity and accelerates elastin degradation in a model of aneurysmal disease.

AIMS: Abdominal aortic aneurysms are characterised by changes in the extracellular matrix of the arterial media, in particular a reduction in elastin concentration. These changes are mediated by increased levels of endogenous matrix metalloproteinases (MMPs). Recently, calcium channel blockers have been shown to increase the proteolytic activity of MMP-2 secreted by vascular smooth muscle cells. It may therefore by hypothesised that calcium antagonists may potentiate the activity of MMPs in aneurysmal disease and thus accelerate AAA expansion. In this study, the ability of amlodipine--a calcium antagonist--to influence elastin degradation, was assessed in a previously described model of aneurysmal disease. METHODS: Porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 micrograms/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections. RESULTS: Gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p < 0.01) and this elevated activity was reflected in a significant destruction of medial elastin 27.0 vs. 40.5% (p < 0.05). CONCLUSION: Therapeutic ranges of amlodipine significantly enhanced elastin degradation and potentiated MMP-9 activity within the aortic organ cultures.

Amlodipine↗

The increasing workload required to maintain infrainguinal bypass graft patency.

BACKGROUND: To assess the impact upon the provision of a vascular service of the workload associated with maintaining infrainguinal bypass graft patency. DESIGN: A computerised prospective audit. MATERIALS AND METHODS: Between January 1990 and December 1995, all patients with infrainguinal bypass grafts were entered into a prospective computerised audit to monitor interventions for the maintenance of graft patency. Excluded from the study were interventions during the first 30 postoperative days and procedures not directly related to the graft. A graft surveillance programme was in operation throughout. RESULTS: During the study period a total of 131 patients with 144 grafts were admitted on 330 occasions and required 401 separate interventional procedures. There were 227 procedures in 72 femorodistal grafts, 116 in 38 below-knee femoropopliteal grafts and 58 interventions in the group of 34 above-knee femoropopliteal grafts. Radiological interventions accounted for almost 70% of this workload. CONCLUSION: The workload associated with the maintenance of infrainguinal bypass grafts increased considerably during the study period, and seems likely to increase further. Such interventions should therefore be considered when planning for vascular service provision.

Anastomosis, Surgical↗

Comparison of computed tomography and duplex imaging in assessing aortic morphology following endovascular aneurysm repair.

BACKGROUND: Computed tomography (CT) has been used to assess patients following endovascular aneurysm repair to determine the need for secondary endoluminal or operative procedures. This prospective study compared CT and duplex imaging to evaluate aneurysm morphology following endoluminal aortic grafting. METHODS: Twenty patients were evaluated at regular intervals following successful endoluminal aneurysm repair. CT and duplex scanning were compared in their ability to determine aneurysm and aortic diameter, the presence of perigraft extravasation (endoleaks) and technical defects in the endograft. RESULTS: In 20 patients who were assessed 6 months after operation, duplex imaging identified four endoleaks (two early, two late; one proximal, three distal). In three cases, the aneurysm diameter progressively increased after operation. In patients with a thrombosed aneurysm sac, the aneurysm regressed at a median of 0.40 (range 0.13-0.8) cm per year. The CT findings were similar (median regression 0.43 (range 0-1.0) cm per year), although CT was unable to predict the site of the leak as accurately as duplex imaging. CT demonstrated that the diameter of the juxtarenal aorta increased following endografting. CONCLUSION: Duplex imaging is a less invasive, less costly alternative to CT in the follow-up of patients after endoluminal aortic surgery. Increase in size of the aneurysm sac following endovascular aneurysm repair strongly suggests the presence of an endoleak.

Aged↗

Role of magnetic resonance angiography for assessment of abdominal aortic aneurysm before endoluminal repair.

BACKGROUND: A detailed knowledge of the morphology of the aorta and iliac arteries is an important prerequisite for successful endoluminal abdominal aortic aneurysm (AAA) repair. The best method of preoperative evaluation remains to be determined. METHODS: A prospective study was undertaken between January 1994 and July 1995 to assess the ability of computed tomography (CT), magnetic resonance angiography (MRA), colour duplex imaging and intra-arterial digital subtraction angiography (IA-DSA) to visualize AAA morphology. RESULTS: Eighty-two consecutive patients (64 men, 18 women) with AAA were assessed with MRA, contrast-enhanced CT, colour duplex imaging and IA-DSA. Median age was 74 (range 59-87) years and median AAA diameter was 5.7 (range 3.5-9.7) cm. Five patients were unable to tolerate CT or MRA examination. Seventy-seven patients underwent both CT and MRA. Of these, 55 also had a colour duplex scan and 32 underwent arteriography. The scans were assessed by an independent blinded observer. MRA was significantly better (P < 0.01) at visualizing AAA morphology compared with CT and colour duplex imaging. There was no statistically significant difference between MRA and arteriography. CONCLUSION: MRA is useful in patient selection for endoluminal AAA repair, as it avoids use of iodinated contrast medium and ionizing radiation.

Aged↗