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Biomedical subjects

John P Fletcher

Publications and source records attributed to John P Fletcher.

9 recordsLinked to original sources

Implications of low great toe pressures in clinical practice.

INTRODUCTION: The aim of this study was to observe the outcome of patients with a great toe pressure (GTP) reading of less than 40 mmHg. METHODS: Between 2002 and 2004, of 4,714 patients assessed in the Westmead Vascular Laboratory, 365 (7.7%) had GTP measurements for assessment of possible critical limb ischaemia. There were 56 limbs in 40 patients with a GTP measurement of less than 40 mmHg, and this group was studied to assess outcome factors of death, requirement for major or minor amputation, arterial reconstructive surgery, clinical stability, or documented improvement from the initial assessment. RESULTS: Patients requiring a major amputation had an average GTP of 13 mmHg and a toe brachial index (TBI) of 0.08, whereas those not undergoing a major amputation had an average GTP of 23.6 mmHg and TBI of 0.15. This association was weaker when an initial single evaluation was used as opposed to two or more serial assessments. Patients with and without a major amputation had an average ankle brachial index of 0.16 and 0.53, respectively. Diabetes mellitus requiring insulin and cerebrovascular disease were risk factors for major amputations. CONCLUSIONS: Low GTP was associated with a greater risk of major amputations. Two or more serial assessments were found to be of greater value than an initial single assessment.

Aged↗

Venous thromboembolism and fractured neck of femur.

The post-operative incidence of venous thromboembolism (VTE) is high for patients undergoing hip fracture surgery. Proven prophylactic measures are available although underutilized due to concern on post-operative bleeding with use of anticoagulants. This study retrospectively reviewed the clinical incidence of VTE and utilisation of thromboprophylactic protocols over an eight year period. Demographic details, mechanism of injury, VTE risk factors, prophylactic modalities (mechanical and pharmacological), operation duration, mode of anaesthesia, hospital length of stay (LOS) and post-operative complications with particular attention to suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were analysed. Male to female ratio was 1:2.7 with a median age of 78 years (IQR: 70-86 years) and 83 years (IQR: 77-87 years) respectively (p<0.001). Median hospital LOS was 8 days (IQR: 5-13 days) and differed with mechanism of injury. The in-hospital incidence of VTE was 1.6% (95% CI: 1.1-2.5%) with a probably underestimated three month rate of 8.2% (95% CI: 5.3-12.4%). Non fatal PE was 0.5% (95% CI: 0.2-1.0%) in-hospital and 2.6% (95% CI: 1.2-5.5%) at three months. Fatal PE was 0.5% (95% CI: 0.2-1.0%) with a three month incidence of 0.4% (95% CI: 0.1-2.4%). The in-hospital VTE incidence was kept relatively low with use of prophylactic protocols with almost all patients receiving prophylaxis by the end of the study period. Given the five-fold out of hospital increase in incidence, consideration should be given to continue prophylaxis beyond hospital discharge in this high risk group of patients.

Aged↗

Hyperglycemia is associated with adverse outcomes in patients receiving total parenteral nutrition.

OBJECTIVE: Hyperglycemia is associated with poor clinical outcomes and mortality in myocardial infarction, stroke, and general hospital patients. However, there are few data regarding the effect of hyperglycemia on outcomes in patients receiving total parenteral nutrition (TPN), a therapy that predisposes patients to hyperglycemia. The aim of this study was to determine whether elevated blood glucose levels are associated with adverse outcomes in patients receiving TPN. RESEARCH DESIGN AND METHODS: A retrospective analysis was undertaken from the medical records of 111 patients (122 treatment episodes) receiving TPN. All patients had blood drawn daily for the measurement of blood glucose levels. Outcome measures were assessed as a function of mean daily blood glucose levels while receiving TPN. RESULTS: Increased blood glucose levels were associated with an increased risk of cardiac complications (odds ratio 1.61, 95% CI 1.09-2.37, P = 0.02), infection (1.4, 1.08-1.82, P = 0.01), systemic sepsis (1.36, 1.00-1.86, P = 0.05), acute renal failure (1.47, 1.00-2.17, P = 0.05), and death (1.77, 1.23-2.52, P < 0.01). When the data were examined by quartiles of blood glucose levels, the mortality of subjects in the highest quartile was 10.9 times (95% CI 2.0-60.5, P < 0.01) that of subjects in the lowest quartile, and the risk of developing any complication was 4.3 times higher (1.4-13.1, P < 0.01). These effects were independent of age, sex, or prior diabetes status. CONCLUSIONS: Hyperglycemia is a predictor of poor outcomes in patients receiving TPN. The confirmation of a relation between blood glucose levels and adverse outcomes provides support for tight glycemic control in these patients.

Adult↗

Antiproliferative effects of low molecular weight heparin.

AIM: To investigate the effect of low molecular weight heparins (LMWH) on the inhibition of intimal hyperplasia (IH) developing in prosthetic vascular patch graft implanted into sheep carotid artery. METHODS: A gelatin sealed Dacron patch graft was implanted into the common carotid artery of sheep, which were then allocated to a control group (n = 10) or to one of four treatment groups (each group n = 10) receiving either a low dose (LD) or high dose (HD) of one of two LMWH (enoxaparin 1 or 2 mg/kg/day, dalteparin 100 or 200 units/kg/day) administered subcutaneously for 4 weeks. Anti-activated factor X and activated partial thromboplastin time were assayed from blood collected prior to and at 1 and 2 h after LMWH administration on days 3, 7, 14, 21 and 28. Animals were killed on day 28 after taking blood samples prior to, then at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h following the last injection. Grafts were collected for analysis and measurements of intimal thickness obtained under light microscopy from eight transverse sections of each grafted artery aided by computer image analysis. An IH index was calculated by dividing the area of IH (mm2) by the width of the graft (mm). RESULTS: Intimal hyperplasia index measurements (mean +/- SD) were: controls 0.574 +/- 0.077, LD enoxaparin 0.471 +/- 0.056, LD dalteparin 0.404 +/- 0.025, HD enoxaparin 0.398 +/- 0.068, HD dalteparin 0.332 +/- 0.048. The reductions in IH index compared to controls were significant (P < 0.05) for both LD and HD dalteparin and for HD enoxaparin. CONCLUSION: Both LMWH dalteparin and enoxaparin reduced the amount of IH formation with dalteparin showing a greater effect in the present animal study. The possibility that different LMWH might exert differing antiproliferative effects requires further investigation.

Animals↗

Fluoropolymer coated Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicentre trial.

BACKGROUND: This trial was designed to compare graft patency between expanded polytetrafluoroethylene (PTFE) and fluoro-polymer coated Dacron for femoropopliteal bypass in patients in whom saphenous vein was unavailable. METHODS: A multicentre prospective trial randomized 129 patients (74 men, 55 women) who underwent femoropopliteal bypass using either a PTFE or fluoropolymer coated Dacron graft. The indication for operation was disabling claudication in 68 (52.7%) and critical limb ischaemia in 61 (47.3%) patients. Distal anastomosis was above the knee in 76 (58.9%) and below the knee in 53 (41.1%) patients. RESULTS: Primary patency at 6, 12 and 24 months was 71%, 56% and 47% for PTFE and 50%, 36% and 36% for fluoropolymer coated Dacron (P = 0.002), respectively. Secondary patency at 6, 12 and 24 months was 77%, 60% and 48% for PTFE and 66%, 49% and 46% for fluoropolymer coated Dacron (P = 0.13), respectively. The superior primary patency of PTFE over fluoropolymer coated Dacron was most evident in patients with poor prognostic indicators for graft survival: critical limb ischaemia (P = 0.001); below-knee anastomosis (P = 0.01); and smaller (6 mm) diameter grafts (P = 0.002). Graft thrombosis developed in the first month in 22 of 61 (36%) patients receiving fluoropolymer coated grafts compared to six of 68 (8.8%) patients receiving PTFE, which accounts for the difference in primary patency. Successful thrombectomy in 10 of the 22 fluoropolymer coated grafts resulted in similar secondary patency. CONCLUSION: Polytetrafluoroethylene has superior primary patency and similar secondary patency to fluoropolymer coated Dacron. These results support the preferential use of PTFE in patients with critical limb ischaemia, especially when a below-knee distal anastomosis and smaller diameter graft is required.

Aged↗

New methodology for assessment of intimal hyperplasia of vascular prostheses.

BACKGROUND: When investigating the degree of formation of intimal hyperplasia (IH) quantification of the extent of the lesion is crucial to its assessment and analysis. The aim of the present study was to establish a new methodology (IH index) for estimating the degree of IH associated with vascular prosthesis implantation. METHODS: Ten female Merino sheep underwent a standard gelatin sealed Dacron (GSD) patch grafting procedure in the left common carotid artery. The grafts were harvested 4 weeks following implantation and processed for assessment of IH by two methodologies - mean intimal thickness (MIT) and IH index. The advantages and disadvantages of the two methods for expressing the degree of IH were compared. RESULTS: The IH index is less labour intensive but is as accurate as the MIT method in quantifying the IH lesion, statistical analysis showing high correlation and measurement agreement between the two methods. CONCLUSION: The IH index is a labour saving standardized methodology for quantification of IH in the current animal model.

Animals↗

Vascular closure staples reduce intimal hyperplasia in prosthesis implantation.

BACKGROUND: Vascular surgery, like the various other surgical specialities, has seen an increasing demand toward faster and more minimally invasive procedures. One such need is to create a reliable vascular anastomosis that is faster, easier and less damaging to the tissue. The vascular closure staples (VCS*) device provides such characteristics but, to date, no studies have investigated its effectiveness in reducing intimal hyperplasia when used for vascular prosthesis implantation. The present study evaluated its effectiveness compared with suturing of a graft in vascular prosthesis implantation. METHODS: Twelve female Merino sheep underwent gelatin sealed Dacron patch graft implantation into the left and right common carotid artery. Grafts were randomly allocated so that one carotid artery and graft was anastomosed using sutures and the other with VCS*. The two techniques were compared for operation time, clip/suture numbers and blood loss during the implantation procedure. After a 4-week period, the sheep were killed and the grafts were harvested for intimal hyperplasia (IH) assessment. RESULTS: There was a significant reduction in the amount of IH seen in the VCS* group (mean +/- SD: 0.278 +/- 0.079 mm2/mm) when compared with the sutured group (0.575 +/- 0.331 mm2/mm) (P < 0.05). There was also significant reduction in anastomosis time (mean +/- SD: 14 +/- 4.4 min) and fewer points of contact (23 +/- 1.4) using the VCS* compared with suturing (22 +/- 3.2 min, P < 0.01; 27 +/- 3.3, P < 0.05, respectively). CONCLUSIONS: In this model, the VCS* shows several distinct advantages over suturing with significant time saving at operation and, most importantly, the reduction of IH seen at 1 month.

Anastomosis, Surgical↗

Perigraft adventitia and intima remodeling after synthetic patch implantation in sheep carotid artery: role of apoptosis and proliferation.

BACKGROUND: The mechanisms of neointima formation after synthetic vascular grafting are not clear. The aim of this study was to investigate the intima and perigraft adventitia remodeling process in terms of cell apoptosis versus proliferation after synthetic patch implantation. METHODS: Female Merino sheep were randomized equally into two groups and underwent implantion with a patch of gelatin sealed Dacron graft into the left common carotid artery. At 1 and 6 months, grafted vessels were harvested, processed, and assessed. Intimal area and lumen sizes were measured with histologic assessment of eight segments from each animal assisted with image analysis. Immunohistochemical labeling of alpha-actin and D33 desmin was performed on tissue sections of perigraft adventitia, graft matrix, and intima. Cell proliferation and cell phenotype were determined with double immunohistochemical staining with anti-proliferating cell nuclear antigen and anti-alpha-actin or antimacrophage antibodies (HAM 56) in perigraft adventitia, graft matrix, and intima. Apoptosis was detected with in situ terminal deoxynucleiotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-fluorescence nick end labeling (TUNEL) in perigraft adventitia, graft matrix, and intima. RESULTS: The carotid artery lumen size at 6 months was significantly larger than at 1 month (P <or=.05). The intimal area was significantly reduced at 6 months compared with 1 month (P <.05). At 1 month and 6 months, perigraft adventitia, graft matrix, and intima showed positive alpha-actin expression but negative desmin staining. In the anastomotic area, a small number of intimal cells suggested their muscle origin (expression alpha-actin and desmin). The number of proliferating cells in the intima was significantly greater at 1 month than at 6 months (P =.01). TUNEL-positive cells were significantly greater in the intima at 1 month than at 6 months (P <.05), whereas TUNEL-positive cells were significantly greater at 6 months in the perigraft adventitia (P <.05). HAM 56-positive cells in the intima at 1 month were significantly greater compared with 6 months (P <.05), whereas in graft and perigraft regions, no significant difference was seen between 1 month and 6 months. CONCLUSION: The cell proliferation and cell phenotype change in intima and perigraft adventitia are associated with thickening of perigraft adventitia and intima at 1 month. The balance between cell proliferation and apoptosis could account in part for the reduction in intima area and perigraft adventitial cellularity at 6 months.

Actins↗