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Biomedical subjects

M J Gough

Publications and source records attributed to M J Gough.

At least 19 recordsLinked to original sources
PubMed2002

Bacterial colonisation of Doppler probes on vascular surgical wards.

AIM: hospital acquired infections cost the NHS 1 pound sterling billion each year and medical equipment may act both as source and vector of nosocomial infection. This study examined bacterial contamination of Doppler ultrasound probes (USP) in routine use on vascular surgical wards in six hospitals and the knowledge of staff about the potential for cross infection from contaminated probes. METHODS: probe head impressions and swab cultures of probe holders were plated on mannitol salt agar before and after cleaning with a paper towel. Putative S. aureus isolates were identified to species level and susceptibility to selected antimicrobials tested. Concurrently, junior medical staff were surveyed about probe cleaning protocols. RESULTS: methicillin susceptible S. aureus was isolated from 2/21 (10%) with near confluent bacterial growth from six others (28%). The latter may have obscured low numbers of S. aureus. Further since swabs were plated without prior enrichment culture, it is likely that contamination with S. aureus might have been underestimated. No positive cultures were obtained after wiping the USP with a paper towel. 22/23 (95%) junior doctors failed to clean the USP prior to use. CONCLUSION: USP contamination with pathogenic bacteria occurs under "in-use" conditions and junior medical staff are unaware of simple measures to prevent this. Strict guidelines for USP cleaning between patient use should, therefore, be adopted particularly when monitoring postoperative graft patency.

Colony Count, Microbial↗
PubMed2001

Macrophages orchestrate the immune response to tumor cell death.

The mechanisms by which the immune system distinguishes normal developmental cell death from pathological immunogenic cell killing are central to effective cancer immunotherapy. Using HSVtk suicide gene therapy, we showed that macrophages can distinguish between tumor cells dying through classical apoptosis and tumor cells engineered to die through nonapoptotic mechanisms, resulting in secretion of either immunosuppressive cytokines (interleukin 10 and transforming growth factor beta) or inflammatory cytokines (tumor necrosis factor alpha or interleukin 1beta), respectively. Additionally heat shock protein 70 acts as one component of a bimodal alarm signal that activates macrophages in the presence of stressful, immunogenic tumor cell killing. These differential responses of macrophages can also be used to vaccinate mice against tumor challenge, using adoptive transfer, as well as to cure mice of established tumors.

Animals↗
PubMed2001

Renal carcinoma cell lines inhibit natural killer activity via the CD94 receptor molecule.

MHC class I molecules protect normal and transformed cells from lysis by natural killer (NK) cells through recognition of receptors expressed on leucocytes. Defects in NK cell activity and lymphokine activated killer (LAK) cell generation have been previously demonstrated in patients with renal cell carcinoma (RCC). However, to date, the importance of NK receptor/MHC class I interactions for immune evasion by RCC cells has not been described. In this study, human RCC cell lines (HTB46, HTB47, ACHN, CRL 1933 and HTB44) were found to be susceptible to lysis by both NK cells and interleukin-15 (IL-15)-derived LAK cells from normal donors in vitro. However, when NK cells were co-cultured with RCC cells their expression of the CD94 NK receptor molecule was significantly increased and their cytolytic activity against RCC targets was reduced. The cytolytic activity of NK cells was restored by the addition of IL-15, which further augmented the expression of CD94 on CD56+ NK cells. Disruption of NK receptor-MHC class I interactions by the addition of blocking antibodies to CD94 had no effect on the lysis of K562 or HTB47 targets by NK cells. However, the sensitivity of HTB46 cells to NK-mediated lysis was increased by blocking the CD94 receptor molecule, but only when the NK cells had not been previously co-cultured with RCC cells. This was independent of the presence of IL-15. These results show that RCC cells can inhibit NK activity via CD94 and suggest that disruption of interactions between receptor and ligand on RCC cells in vivo may augment the immune response against tumours by innate effector cells.

Antibodies, Monoclonal↗
PubMed2001

Differences in the detection of cyclo-oxygenase 1 and 2 proteins in symptomatic and asymptomatic carotid plaques.

BACKGROUND: The expression of cyclo-oxygenase (COX) 1 and 2 has been demonstrated in atherosclerotic arteries. In the present study this was correlated with symptoms arising from a carotid plaque. METHODS: Carotid plaques from 12 asymptomatic patients were compared with 11 plaques from patients who had had neurological symptoms within the preceding 30 days. Sections were stained with haematoxylin and eosin, elastin van Gieson and goat antihuman antibodies to COX-1 and COX-2. Plaque morphology was correlated with neurological symptoms. The area with positive COX-1 and COX-2 staining was measured by computerized planimetry in entire cross-sections and in specific areas of the plaque. RESULTS: There was a significant association between cap thinning and plaque rupture with symptoms (P = 0.003). The percentage area of positive staining in entire cross-sections for both COX-1 and COX-2 was significantly greater in symptomatic plaques (P = 0.001 and 0.0004 respectively). Staining in symptomatic plaques was significantly greater in the cap (COX-1: P = 0.001; COX-2: P = 0.0001) and shoulder (COX-1: P = 0.008; COX-2: P = 0.007) regions of the plaque. COX-1 expression in the sclerotic area was not increased (P = 0.15) although COX-2 staining was significantly greater (P = 0.04). CONCLUSION: Both COX-1 and COX-2 detection was increased in symptomatic plaques. COX may contribute to plaque rupture and the onset of symptoms.

Aged↗
PubMed2001

Vascular surgeon's experience with intraoperative angioplasty.

BACKGROUND: Intraoperative balloon angioplasty as an adjunct to vascular reconstruction is controversial and radiologists suggest that it may be less effective than preoperative or postoperative percutaneous transluminal angioplasty. The aim of the present study was to explore the role of intraoperative balloon angioplasty as performed by a vascular surgeon. METHODS: The notes and angiograms of 63 patients on whom 67 intraoperative angioplasty/stenting procedures were performed were retrieved using a computerized prospective audit system. RESULTS: Although 41 procedures were planned preoperatively, 26 (39%) followed intraoperative angiography. Twenty-seven were performed to improve inflow for distal reconstructions and 27 were performed to improve outflow for proximal reconstructions. Thirteen (anastomotic stenoses) followed synthetic graft thrombectomy. Twenty-seven iliac, 15 superficial femoral artery (SFA), 11 popliteal, one anterior tibial and 13 anastomotic lesions were dilated and there were four technical failures. At follow up (median: 24 months; 3-monthly duplex scan, ankle brachial pressure indices) primary patency rates by lifetable analysis were: iliac, 75%; SFA, 91%; popliteal, 82%; anastomotic, 8%. CONCLUSIONS: There are situations in which intraoperative angioplasty would be advantageous and can be performed successfully by a surgeon. Because a significant proportion of procedures was unplanned and a vascular radiologist was not readily available the authors conclude that vascular surgical trainees should be trained in angioplasty techniques. However, balloon angioplasty is ineffective in treating anastomotic stenoses and surgical intervention is required for these lesions.

Adult↗
PubMed2001

Carotid endarterectomy; local or general anaesthesia?

OBJECTIVES: to review the evidence for theoretical and clinical benefits of local or general anaesthesia for carotid endarterectomy. METHODS: literature review. RESULTS: animal studies suggest cerebral protection by a variety of general anaesthetic agents but clinical evidence is lacking. There is some clinical evidence that normal cerebral protective reflexes are preserved with local anaesthesia. Shunt insertion is the most widely used method of providing cerebral protection with awake testing the most reliable monitoring technique for the identification of ischaemia. There are therefore theoretical arguments for a reduced risk of perioperative stroke when local anaesthesia is used and this is supported by a meta-analysis of non-randomised studies. Intraoperative blood pressure is always higher with local anaesthesia but the incidence of postoperative haemodynamic instability seems to be independent of anaesthetic technique. There is little evidence that myocardial ischaemia is more common with either anaesthetic technique but meta-analysis of non-randomised again suggests fewer cardiac complications with local anaesthesia. Cranial nerve injury and haematoma formation may be less common with local anaesthesia but the evidence is weak. There is no evidence that surgery is more difficult with local anaesthesia or that it is poorly tolerated by the patients. CONCLUSIONS: there are theoretical arguments and clinical evidence that the outcome from carotid endarterectomy may be better when local anaesthesia is used with no significant disadvantages. An appropriately designed randomised trial is required to confirm this.

Anesthesia, General↗
PubMed2001

Skeletal muscle ischaemia-reperfusion injury: further characterisation of a rodent model.

BACKGROUND: Postischaemic damage in skeletal muscle may be reflected in changes to microvascular blood flow, vascular permeability, and subsequent tissue viability. Previous preclinical studies have not addressed all these parameters, and have not used periods of ischaemia and reperfusion relevant to the clinical setting. This study aimed to develop an animal model hindlimb ischaemia-reperfusion to simulate acute lower limb ischaemia. METHODS: A rodent model of hindlimb tourniquet-induced ischaemia-reperfusion was employed. Gastrocnemius muscle blood flow (GMBF; radio-labelled microspheres), oedema (GMO; using a wet:dry ratio method) and viability (GMV; histochemistry and computerised planimetry) were quantified. RESULTS: 6 h ischaemia per seresulted in neither muscle oedema nor loss of viability, but these changes were apparent following 4 h reperfusion. Early reperfusion at 10 min demonstrated low reflow, with GMBF improving at 120 min before declining sharply at 240 min. CONCLUSION: Prolonged hindlimb ischaemia followed by reperfusion in this rodent model caused significant reductions in gastrocnemius muscle blood flow, associated with muscle oedema and necrosis. These three parameters have not been previously reported together in the same model. This reproducible model could be used in the evaluation of potential therapeutic intervention strategies aimed at ameliorating skeletal muscle reperfusion injury.

Animals↗
PubMed1999

Macrophage accumulation within the cap of carotid atherosclerotic plaques is associated with the onset of cerebral ischemic events.

PURPOSE: Macrophage accumulation is associated with aortic and coronary plaque instability. The macrophage content of carotid plaques removed at carotid endarterectomy (CE) was assessed, and the relevance to the onset of ipsilateral cerebral ischemic events (CIE) was examined. METHODS: Carotid plaques from patients undergoing CE were examined (group I, symptomatic stenoses, n = 28; group II, high-grade asymptomatic stenosis, n = 7). The plaques were stained with monoclonal antimacrophage antibody (HAM56), and the interval since the last CIE was recorded. The percentage area of the cap, shoulder, and entire sclerotic region was quantified by computerized planimetry. RESULTS: The macrophage content of the cap, shoulder, and sclerotic region in all 35 plaques was 1.14% (interquartile range, 0.56 to 3.86), 1.03% (0.51 to 2.15), and 0.49% (0.27 to 0.63), respectively (cap vs sclerotic, P <.01; shoulder vs sclerotic, P <. 01; cap vs shoulder, P =.23). In 18 plaques that were removed less than 180 days after the last CIE, the macrophage content of the cap, shoulder, and entire sclerotic region was 2.41% (0.95 to 4.81), 0. 83% (0.40 to 2.52), and 0.53% (0.38 to 0.71), respectively (cap vs sclerotic, P =.01; cap vs shoulder, P =.01). The content in the cap of these plaques was greater than in plaques removed more than 180 days after symptoms, or asymptomatic plaques (n = 17; 0.62% [0.44 to 1.25], P =.01). The cap macrophage content was inversely related to the time since the last CIE (r = -0.414, P =.029). CONCLUSION: In patients requiring CE, macrophage accumulation was maximal within the cap of carotid plaques and greatest in plaques removed less than 180 days after the last CIE. These findings and the inverse relationship between macrophage content and the interval since symptoms support the hypothesis that macrophage accumulation is associated with plaque instability.

Aged↗
PubMed1999

Does hypothermia prevent cerebral ischaemia during cardiopulmonary bypass?

It is believed that moderate hypothermia (25-32 degrees C) during cardiopulmonary bypass provides cerebral protection by reducing the cerebral metabolic rate (CMRO2). Nevertheless episodes of ischaemia do occur and thus it has been suggested that cerebral oxygenation should be monitored by jugular venous oximetry. However, this technique is cumbersome and invasive. Near infrared spectroscopy (NIRS) provides a non-invasive assessment of cerebral oxygenation and this was used together with continuousjugular venous oximetry in 21 patients undergoing hypothermic cardiopulmonary bypass. During the hypothermic period, jugular venous oximetry indicated reduced oxygen extraction consistent with a reduction in CMRO2 (increase from 61 +/- 2.5% to 74 +/- 2.5%). In contrast, near infrared spectroscopy demonstrated increased oxygen extraction (HbO2 - 11.5 +/- 1 microM, HHb + 3.2 +/- 0.3 microM) and a fall in the cerebral concentration of oxidized cytochrome oxidase ( - 1.7 +/- 0.3 microM) indicating ischaemia. These results suggest that cerebral ischaemia occurs during hypothermic cardiopulmonary bypass with a spurious rise in jugular venous oxygen saturation, which represents arterio-venous shunting. Thus if hypothermia does facilitate cerebral protection it does not appear to be a direct result of a reduction in CMRO2 and oxygen requirement.

Adult↗
PubMed1999

Do prostaglandins have a salutary role in skeletal muscle ischaemia-reperfusion injury?

OBJECTIVES: the effects of prostaglandins (PG) E1, E2, and the prostacyclin analogue iloprost with and without the addition of free-radical scavengers catalase and superoxide dismutase on gastrocnemius blood flow and oedema were studied in a rodent model of hindlimb ischaemia-reperfusion. METHODS: male Sprague-Dawley rats underwent 6-h hindlimb ischaemia with 4-h reperfusion. Prostaglandins were infused prior to reperfusion and their effects on limb blood flow and oedema examined. RESULTS: control animals exhibited a triphasic pattern of muscle blood flow during reperfusion compared to normal animals. PGE1 did not abolish low reflow at 10 min, relative reperfusion was preserved but reperfusion injury was abolished at 120 min. Muscle blood flow was increased at 240 min compared to controls. Increased limb swelling was also seen. Addition of free-radical scavengers caused the abolition of low reflow. Similar results were seen with iloprost. PGE2 abolished low reflow at 10 min and increased perfusion at 120 min but did not prevent reperfusion injury at 240 min. CONCLUSIONS: PGE1 and iloprost enhance muscle blood flow at 4-h reperfusion, though neither abolishes low reflow; PGE2 improved flow at 10 and 120 min but not after 240 min. This study demonstrates a potentially beneficial role for prostaglandins in improving muscle blood flow in skeletal muscle ischaemia-reperfusion injury.

Alprostadil↗
PubMed1998

A late complication of internal carotid artery stenting.

Carotid angioplasty and stenting is gaining in popularity as an alternative to carotid endarterectomy for the treatment of symptomatic critical stenoses of the internal carotid artery. However, the durability of this technique and the incidence of recurrent stenoses has not yet been fully evaluated. It has been reported that mechanical factors may cause deformity of a Palmaz stent, negating the initial benefits of the procedure. We describe successful carotid endarterectomy after distortion of a Strecker balloon-expandable stent.

Angioplasty↗
PubMed1998

The role of the neutrophil in ischaemia-reperfusion injury: potential therapeutic interventions.

The pathogenesis of the reperfusion syndrome is complex and as yet not fully elucidated. It is characterized by the development of increased microvascular permeability, oedema and tissue necrosis, and is associated with free radical release, cellular calcium overload and activation of neutrophils. Furthermore, systemic release of putative mediators may result in distant organ injury (lung, kidney, heart). This review, after briefly describing the role of neutrophils in these events, will concentrate on potential therapeutic interventions that might be employed to minimise ischaemia-reperfusion syndrome. Issues of safety will be considered, and potential applications of these techniques in patient management discussed.

Animals↗
PubMed1998

Monitoring the effects of heparin: evaluation of a new portable device.

The aim of this study was to measure the effects of heparin therapy in patients undergoing vascular surgery, and to monitor the effectiveness of continuous intravenous heparin therapy in ward-based patients. In addition, we compared results from a new portable device with those from the standard laboratory assay. A prospective comparison of the two methods in patients undergoing peripheral vascular surgery, and in ward-based patients who were receiving intravenous heparin infusions was undertaken. Fifty patients who were undergoing vascular surgery and receiving a bolus dose of intravenous heparin, and 22 patients receiving a continuous heparin infusion, were recruited. Blood samples were taken 10 and 40 min following bolus heparin administration or after > 12 h of a continuous heparin infusion. Plasma activated partial thromboplastin times (APTTp) measured by the haematology laboratory were compared with whole blood (APTT(B)) ascertained with the CoaguChek Plus Device (Boehringer Mannheim UK Diagnostics and Biochemicals Limited) at each time point. The results from the two methods were compared using the method of Bland and Altman (Lancet, 1986, 307-310). We found a good level of agreement between the two methods (at induction, mean bias was -0.050, limits of agreement -0.46 - 0.36; heparin infusions, mean bias was -0.283, limits of agreement -1.64 - 1.07). In addition we discovered that many of our patients appeared to be excessively anticoagulated during surgery (10 min following heparin bolus 47/50 patients had an APTT(B) > 150 s, 45/50 had an APTTp > 250 s; at 40 min 45/50 had an APTT(B) > 150 s, 39/50 had an APTTp > 250 s). In conclusion, whole blood APTT measurement allows rapid and accurate assessment of the effects of heparin therapy when compared with laboratory APTT measurement and may prevent both excessive and suboptimal anticoagulation.

Anticoagulants↗