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Biomedical subjects

M M Thompson

Publications and source records attributed to M M Thompson.

At least 19 recordsLinked to original sources
PubMed2003

The abdominal compartment syndrome following aortic surgery.

BACKGROUND: multi-organ failure is a leading cause of death following aneurysm surgery, especially in the emergency setting. Intra-abdominal hypertension is an important factor in the development of multi-organ failure. Prevention, early recognition and prompt treatment of abdominal hypertension and the abdominal compartment syndrome may reduce mortality following aneurysm surgery. METHODS: a descriptive review of the literature from a Medline search. RESULTS AND CONCLUSIONS: the abdominal compartment syndrome is the result of diverse physiological effects caused by increased intra-abdominal pressure. The syndrome has been most widely described in trauma victims, but occurs in patients following aortic surgery, particularly following ruptured aneurysm repair. Preventative therapy should be instituted to minimise its development in patients at risk, and monitoring of intra-abdominal pressure may allow prompt treatment of this condition.

Abdomen↗
PubMed2003

The acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in vascular patients.

OBJECTIVE: the aim of this study was to establish at which point during a hospital admission MRSA acquisition occurs in vascular patients. METHOD: a consecutive series of 100 patients undergoing arterial surgery were screened for MRSA carriage on admission to hospital, on exit from theatre, on discharge from ITU, weekly whilst an inpatient and on hospital discharge. Screening was with moistened swabs from nose, throat, perineum and open wounds that were pooled for microbiological culture. RESULTS: four patients (4%) screened positive for MRSA on admission to hospital. Of the remaining 96, 16 (17%) acquired MRSA during their hospital stay as follows: exit from theatre, one; exit from ITU, six; on the ward postoperatively, nine. Comparing MRSA acquisition (n=16) with non acquisition (n = 80) the following characteristics were noted, length of stay 16 (4-66) vs 7 (2-50) days (Mann-Whitney p < 0.001); admission to ITU 13/16 vs 46/80 (Fishers chi-squared p = 0.10); length of ITU stay 3 (1-20) vs 3 (1-14) days (Mann-Whitney p = 0.41). Frequent hospital attendance, age, emergency admission, diabetes or renal failure were not commoner in those with MRSA acquisition. CONCLUSIONS: these data indicate that 4% of patients undergoing arterial surgery are pre-existing carriers of MRSA. Length of hospital stay is the single most important determinant of MRSA acquisition.

Adult↗
PubMed2002

Matrix metalloproteinases and atherosclerotic plaque instability.

BACKGROUND: There is growing interest in the role of matrix metalloproteinases in atherosclerosis. Excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic plaque disruption, a frequent predeterminant of ischaemic cardiac events and stroke. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. METHODS: The core of this review is derived from a Medline database literature search. RESULTS: There is convincing evidence of increased matrix metalloproteinase activity during acute plaque disruption. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in models of vascular disease suggest a potential therapeutic benefit. CONCLUSION: In vivo studies of matrix metalloproteinase inhibition are required to study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies acute plaque disruption.

Arteriosclerosis↗
PubMed2002

Prosthetic patch infection after carotid endarterectomy.

OBJECTIVES AND DESIGN: prospective audit of the management and outcome of prosthetic patch infection after carotid endarterectomy (CEA) at Leicester Royal Infirmary plus review of the literature. RESULTS: 8/936 CEA patients (0.85%) developed a prosthetic patch infection. Responsible organisms included MRSA (n=3), Staphylococcus epidermidis(n=2), haemolytic Streptococcus (n=1), Staphylococcus aureus(n=1) and Pseudomonas (n=1). Early wound complications preceded 4/5 infections presenting within 9 weeks of surgery. In addition to systemic antibiotics and debridement, management included patch removal and: (i) carotid ligation (n=3), vein patch repair (n=1), vein bypass (n=3). One patient had antibiotic irrigation of the in-situpatch. No patient died, one suffered a disabling postoperative stroke and two had temporary cranial nerve injuries. Including this series, a literature review identified 43 prosthetic patch infections, 91% culturing Staphylococci or Streptococci. Cumulative freedom from perioperative stroke/death or re-infection was 65% at 2 years. Patients treated by patch excision and autologous venous reconstruction had the best outcome with a cumulative freedom from perioperative stroke/death or re-infection of 91% at 2 years. CONCLUSION: prosthetic patch infection after CEA is rare. This study emphasises the importance of close surveillance of early wound complications. Surgical decision-making, especially the safety of carotid ligation, was facilitated by access to transcranial Doppler.

Bacterial Infections↗
PubMed2002

Enhanced invasive properties exhibited by smooth muscle cells are associated with elevated production of MMP-2 in patients with aortic aneurysms.

BACKGROUND: abdominal aortic aneurysms (AAA) are associated with excessive vascular matrix remodelling. Recent findings suggest a systemic overproduction of matrix metalloproteinases-2 (MMP-2) by vascular smooth muscle cells (SMC) may be pivotal aetiologically. SMC migration is facilitated by MMP mediated proteolysis of the basement membrane and extracellular matrix. Our aim was to see if enhanced MMP-2 production by these SMC exhibit increased invasion, in an in vitro model of migration. METHOD: SMC were derived from inferior mesenteric vein (IMV) harvested from patients undergoing aneurysm repair (n=6) or colectomy for diverticulosis (n=6, control). Using a modified Boyden chamber chemotaxis was measured towards platelet derived growth factor (PDGF) and foetal calf serum (FCS) and invasion through a Matrigel layer. MMP-2 production was quantified by ELISA and gelatin zymography. RESULTS: chemoattractant studies demonstrated no difference in the effect of PDGF or FCS between the two populations of SMC. However, invasive studies demonstrated a significant increase in the number of migrating SMC isolated from IMV of AAA patients. Analysis of culture media extracts revealed that this difference was associated with a significant increase in production of MMP-2. CONCLUSION: SMC derived from patients with AAA demonstrate increased invasive properties when compared to a control group. Increased migration appears to be due to overproduction of MMP-2. The enhanced migratory potential of these SMC may lead to extracellular matrix remodelling and subsequent medial disruption demonstrated in the aneurysmal aorta. These data further support evidence of the proteolytic role of MMP-2 in cell migration.

Aortic Aneurysm, Abdominal↗
PubMed2002

Endovascular repair of wide neck AAA--preliminary report on feasibility and complications.

AIM: To assess the feasibility of endovascular repair (EVR) of wide neck abdominal aortic aneurysms (AAA). STUDY DESIGN: Retrospective. METHOD: A cohort of patient was identified who had an AAA neck diameter of 28 mm or more and underwent EVR. These patients undergo regular follow-up by 6 monthly CT scan of abdominal aorta. Two independent observers quantified the diameter of the suprarenal aorta, the top of the neck, the bottom of the neck, the length of the neck and the transverse diameter of the AAA. RESULTS: The study cohort comprised 16 patients. Bland Altman Analysis determined that the 95% interobserver limits of agreement were -4.7 to 3.3 mm. The mean preoperative diameter of the suprarenal aorta, the top of the neck and bottom of the neck all were 31 mm. On the follow-up CT scan on average after 12 months the suprarenal aorta measured 29 mm, the top of the neck 28 mm and the bottom of the neck 30 mm. There was a statistically significant decrease in the size of the top of the neck (p = 0.03). CONCLUSION: This preliminary report suggests that the endovascular repair of AAA with a wide neck is feasible with available commercial devices. The necks do not appear to increase in size and there is no increased incidence of proximal endoleak.

Aged↗
PubMed2002

The role of matrix metalloproteinases in vascular disease.

There is growing interest in the role of matrix metalloproteinases in vascular diseases. These conditions are often characterized by excessive tissue remodelling, and increased matrix metalloproteinase activity has been demonstrated in aneurysms, intimal hyperplasia and atherosclerotic plaque disruption. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. The core of this review is derived from a MEDLINE database literature search. The review found that there is convincing evidence of increased matrix metalloproteinase activity in a spectrum of vascular disease. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in vascular disease models suggest potential therapeutic benefit. In conclusion, in vivo studies of matrix metalloproteinase inhibition are required to further study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies vascular disorders.

Connective Tissue Diseases↗
PubMed2002

Complications following peripheral angioplasty.

BACKGROUND: Peripheral angioplasty is increasingly the first choice intervention in patients with peripheral vascular disease. The aim of the current study was to audit prospectively all major complications, especially the requirement for emergency surgical intervention. PATIENTS AND METHODS: A prospective audit of outcome after peripheral angioplasty in 988 patients undergoing 1377 interventional procedures between 1 October 1995 and 30 September 1998 at which 1619 vessel segments were angioplastied. RESULTS: Major medical morbidity (bronchopneumonia, stroke, renal failure, myocardial infarction) complicated 33/1377 procedures (2.4%). Emergency surgical intervention was required after 31/1377 procedures (2.3%) with the commonest aetiologies being acute limb ischaemia and haemorrhagic complications. The amputation rate following angioplasty was 0.6% and no patient presenting with claudication or graft complications underwent amputation. The amputation rate following angioplasty for critical limb ischaemia was 2.2%. Overall, the risk of death and/or major medical complication and/or requiring emergency surgical intervention was 3.5%. The rate of complications was no different for subintimal as opposed to transluminal angioplasties. CONCLUSIONS: Peripheral angioplasty is associated with a low risk of major medical and surgical complications.

Amputation, Surgical↗
PubMed2001

Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms.

BACKGROUND: Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. METHODS AND RESULTS: Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. CONCLUSIONS: Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.

Aged↗
PubMed2001

Plasma MMP-9 - a marker of carotid plaque instability.

OBJECTIVES: to investigate whether peripheral blood levels of matrix metalloproteinases (MMPs) or their inhibitors are altered in patients with particulate cerebral embolisation. DESIGN: a prospective study. MATERIALS AND METHODS: using sandwich enzyme immunoassay, plasma levels of MMPs-1, -2, -3 and -9, plus TIMPs-1 and -2 were quantified in 70 consecutive patients undergoing carotid endarterectomy. Patients were monitored with transcranial Doppler (TCD) preoperatively and during the dissection phase of the operation to detect those with spontaneous particulate embolisation (n =21). RESULTS: the plasma level of MMP-9 was significantly higher in those patients with evidence of spontaneous embolisation compared to those without. There were no differences in other MMP levels, or plasma concentrations of TIMPs. CONCLUSIONS: plasma MMP-9 levels are elevated in patients with particulate cerebral embolisation, and this may represent a novel marker of atherosclerotic plaque instability.

Aged↗
PubMed2001

The impact of MRSA on vascular surgery.

OBJECTIVES: To investigate the prevalence of MRSA infection in patients treated in a major vascular unit and examine its consequences. DESIGN AND METHODS: A retrospective case-note review was performed. RESULTS: During the period 1993 to 2000, a total of 172 patients (4.4% of total) were positive for MRSA. Of these 97 were colonised and 75 were infected by MRSA. The proportion of wound or graft infections caused by MRSA has increased (4% in 1994 to 63% in 2000). Three patients developed native artery infection (one following aortic stent insertion and 2 following embolectomy). All patients with aortic graft infection died. All patients with infected prosthetic infrainguinal bypass ended up with an amputation. CONCLUSION: The prevalence of MRSA infection is increasing. Infection of aortic grafts appears to be uniformly fatal and lower limb graft infection is associated with high limb loss.

Female↗
PubMed2001

Randomized trial of vein versus Dacron patching during carotid endarterectomy: influence of patch type on postoperative embolization.

PURPOSE: A recent overview indicated that although routine patching is safer than routine primary closure after carotid endarterectomy (CEA), there is no systematic evidence that patch type influences outcome. However, most surgeons still believe that prosthetic patches are probably more thrombogenic than vein patches. This study tested the hypothesis that there was no difference in thrombogenicity between the different patch types. METHODS: A total of 274 patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n = 137) or vein-patch closure (n = 139). All patients with an accessible cranial window were monitored for 3 hours postoperatively with transcranial Doppler scanning (TCD). The number of emboli and rate of embolization were quantified with the requirement for selective dextran therapy to control high rates of postoperative embolization. All patients were assessed postoperatively and again at 30 days by a neurologist, and all patients underwent a duplex examination at 30 days. RESULTS: The 30-day death/any stroke rate was 2.2% for patients in the Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72). Patients in the Dacron-patch group had a higher incidence of postoperative emboli (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group (median, 3; interquartile range, 1-17; P =.028). However, the incidence of detecting more than 50 emboli was virtually identical, and patch type had no effect on the incidence of high-rate, sustained embolization that required dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid thrombosis at 30 days. CONCLUSION: Sustained, high-rate embolization, previously shown to be highly predictive of progression to carotid thrombosis, appears to be patient dependent, rather than related to patch type.

Aged↗
PubMed2000

Simple and reliable method of doxycycline determination in human plasma and biological tissues.

Over recent years there has been a resurgence in the use of doxycycline in clinical practice, which does not depend on its antibacterial properties. This paper describes a method of determination of doxycycline in human plasma and atheromatous tissue using high-performance liquid chromatography (HPLC), and a cheap commercially available extraction system. Doxycycline is extracted in the mobile phase and injected directly into the HPLC system, avoiding time consuming drying up steps. A limit of detection of 0.125 microg/ml of plasma, and a relative standard deviation of 3% was achieved, making the method very reliable and useful for assays within the usual therapeutic range. The method has also been applied to the extraction of a mixture of tetracyclines from plasma and atherma with equal efficacy, making it useful for assays of this class of drugs in veterinary practice and assays of food contaminants.

Anti-Bacterial Agents↗
PubMed2000

Smooth muscle alpha-actin CArG elements coordinate formation of a smooth muscle cell-selective, serum response factor-containing activation complex.

Previous studies have shown that multiple serum response factor (SRF)-binding CArG elements were required for smooth muscle cell (SMC)-specific regulation of smooth muscle (SM) alpha-actin expression. However, a critical question remains as to the mechanisms whereby a ubiquitously expressed transcription factor such as SRF might contribute to SMC-specific expression. The goal of the present study was to investigate the hypothesis that SMC-selective expression of SM alpha-actin is due at least in part to (1) unique CArG flanking sequences that distinguish the SM alpha-actin CArGs from other ubiquitously expressed CArG-dependent genes such as c-fos, (2) cooperative interactions between CArG elements, and (3) SRF-dependent binding of SMC-selective proteins to the CArG-containing regions of the promoter. Results demonstrated that specific sequences flanking CArG B were important for promoter activity in SMCs but not in bovine aortic endothelial cells. We also provided evidence indicating that the structural orientation between CArGs A and B was an important determinant of promoter function. Electrophoretic mobility shift assays and methylation interference footprinting demonstrated that a unique SRF-containing complex formed that was selective for SMCs and, furthermore, that this complex was probably stabilized by protein-protein interactions and not by specific interactions with CArG flanking sequences. Taken together, the results of these studies provide evidence that SM alpha-actin expression in SMCs is complex and may involve the formation of a unique multiprotein initiation complex that is coordinated by SRF complexes bound to multiple CArG elements.

Actins↗
PubMed2000

Impaired adaptation to renal mass reduction in the polycystic rat.

Autosomal dominant polycystic kidney disease (ADPKD) is a serious cause of renal failure. In many renal-disease models, surgical renal mass reduction accelerates disease progression. We explored whether surgical renal mass reduction and the method of renal mass reduction accelerate the course of ADPKD. Studies were conducted in male heterozygous cystic Han:SPRD rats and unaffected littermate controls. Control and cystic rats were subjected to 50% renal mass reduction by uninephrectomy, 50% renal mass reduction by infarction of half of each kidney, or sham operation. Most groups were followed up to the age of 20 weeks, with serial measurements of blood pressure and proteinuria. At 20 weeks, glomerular filtration rate (GFR) and renal plasma flow (RPF) rate were measured. Similar studies to 12 weeks of age were performed in additional groups of control and cystic rats with either sham operation or 50% renal infarction. In noncystic rats, uninephrectomy led to minimal effects on blood pressure and proteinuria and to substantial compensatory renal hypertrophy, hyperfiltration, and hyperperfusion. Similar renal mass reduction by segmental infarction led to greater values for blood pressure and proteinuria and significant compensatory hyperfiltration. In contrast, the cystic rats showed a significant reduction in baseline renal blood flow, more profound increases in blood pressure and proteinuria, and no compensatory increases in GFR and RPF after reduction of renal mass. These studies suggest that the ability of cystic kidneys to respond to acquired loss of nephrons is impaired and that these kidneys are at greater risk when additional renal injury is superimposed.

Animals↗