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Biomedical subjects

S J Sheehan

Publications and source records attributed to S J Sheehan.

At least 19 recordsLinked to original sources

Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease.

BACKGROUND: Angiogenesis is a recognized feature of the atherosclerotic process and has been described in the context of unstable coronary atherosclerotic lesions. The aim of this study was to assess the association between angiogenesis in atherosclerotic carotid plaques and microscopic features of plaque instability, in particular intraplaque haemorrhage. METHODS: Consecutive patients undergoing carotid endarterectomy were included. Endarterectomy specimens were divided into their constituent atherosclerotic lesions. Histological sections were prepared and stained with haematoxylin and eosin, and immunohistochemically with an endothelial cell marker (CD34). The quantity of intraplaque haemorrhage was measured in transverse histological sections using computerized image analysis. Microvessel counts were performed in CD34-stained sections and were verified through computerized image analysis. RESULTS: Some 239 atherosclerotic lesions from 73 patients were available for analysis; 73 were early lesions, 74 were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque haemorrhage, of which 28 involved less than 50 per cent of the plaque sectional area. There were higher microvessel counts in plaques containing over 50 per cent haemorrhage (P < 0.0001), unstable atherosclerotic lesions (P < 0.0001) and atherosclerotic lesions obtained from symptomatic patients (P < 0.001). CONCLUSION: There are strong associations between plaque vascularity, quantity of intraplaque haemorrhage and presence of symptomatic carotid occlusive disease.

Aged↗

The effects of recombinant human growth hormone on cardiopulmonary function in elective abdominal aortic aneurysm repair.

OBJECTIVES: Cardiorespiratory complications are the predominant source of morbidity in patients undergoing major surgery. Recombinant human growth hormone (rhGH) has previously been shown to be effective in improving respiratory and cardiac function in compromised patients. DESIGN: The aim of this study was to assess the effects of perioperative rhGH on cardiac function in 33 patients undergoing elective infrarenal abdominal aortic aneurysm repair. METHODS: Patients were randomised to one of three groups: placebo for 6 days before and after surgery (control, n = 12); genotropin (GH) 0.3 units/kg/day for 6 days before and after surgery (pre and postop GH, n = 10) and placebo for 6 days before and GH (0.3 units/kg/day) for 6 days after surgery (postop EH, n = 11). Patients were assessed on days 7 and 1 before and days 7, 14 and 50 after operation. Intraoperative cardiac index (CI) was measured after induction of anaesthesia, before and after aortic cross-clamping, after aortic unclamping and at the end of surgery. RESULTS: Pretreatment with GH resulted in a significantly higher heart rate during surgery and was associated with a trend towards higher cardiac index (CI) (p < 0.067) at all stages of surgery. Mean arterial blood pressure at the stage of aortic unclamping was significantly higher in patients treated with GH preoperatively. CONCLUSIONS: Larger studies are required to evaluate the beneficial effects of GH in aortic surgery. However, data from this pilot study suggests that perioperative GH administration may result in improved cardiac performance during aortic surgery.

Aged↗

Recurrent varicose veins.

Recurrence of varicose veins after treatment has been reported as being between 7% and 65%. During the five month period from August to December 1993, 400 operations on 265 patients were performed for varicose vein disease. Of these, 53 patients had presented with recurrent vein disease in 72 limbs (18%). All patients underwent Duplex scanning of their deep and superficial systems and sites of venous incompetence were identified. The sapheno-femoral junction (SFJ) was found to be incompetent in 52 limbs, of which 31 had previously undergone flush ligation. Sapheno-popliteal junction (SPJ) was incompetent in 33 limbs, while the long saphenous vein (LSV) was found to be incompetent in 67 cases. There were no major complications in this group. Minor complications occurred in 10 cases (14%), mainly in the form of thigh paraesthesia. The more common causes of recurrent disease have been identified and therefore, it should be possible to reduce its incidence. Duplex scanning is essential for any unit dealing with recurrence.

Adult↗

Differential effects of lower limb revascularisation on organ injury and the role of the amino acid taurine.

Lower torso revascularisation following ischaemia results in a systemic inflammatory response. Endothelial barrier function is disrupted by neutrophil-derived proteases and oxidants. Taurine, an amino acid found in large quantities in neutrophils, is a powerful endogeneous anti-oxidant. The aims of this study were to investigate the systemic effects of reperfusion following lower limb revascularisation and to evaluate the role of taurine administration in preventing this injury. A rat model of aortic occlusion (30 min) followed by 2 h of reperfusion was used. Animals were randomised to one of three groups (n = 10 per group): control; ischaemia reperfusion untreated (IR) and taurine-treated. Taurine (4% solution) was administrated orally for 48 h prior to the experiment. Neutrophil infiltration and microvascular permeability were assessed by measuring tissue myeloperoxidase activity and wet/dry weights respectively in lung, liver, kidney, and in cardiac and skeletal muscle. Statistical analysis was by means of analysis of variance (ANOVA). Reperfusion resulted in pulmonary and renal microvascular injury as assessed by organ oedema. Hepatic tissue, skeletal and cardiac muscle were unaffected by lower limb revascularisation. Taurine was effective in preventing neutrophil-mediated pulmonary but not renal microvascular injury. These data suggest that, whilst reperfusion-induced pulmonary injury is predominantly neutrophil-mediated, agents other than neutrophil-derived oxidative metabolites, capable of independently causing organ injury through direct endothelial damage, are produced during reperfusion.

Animals↗

Plasma factors augment neutrophil and endothelial cell activation during aortic surgery.

Lung injury following reperfusion results from endothelial damage caused by release of cytotoxic products by activated neutrophils (PMN) in the pulmonary microvasculature. This process is facilitated by the release of pro-inflammatory cytokines and arachidonic metabolites following the outset of reperfusion. This study aimed to evaluate the effect of plasma obtained before and after revascularisation on neutrophil and endothelial cell activation. Plasma (IR-plasma) was obtained from venous blood samples taken before and during aortic cross-clamping, and 5, 40 and 60 min following clamp removal in seven patients undergoing elective infrarenal aortic aneurysm resection. PMN from healthy volunteers (n = 5) were incubated with these plasma samples or with fMLP (N-formylmethionyl-leucyl-phenylalanine) as positive control for 30 min and assessed flow-cytometrically for CD11b expression. Human endothelial cells (ECV-304) were incubated with IR plasma for 2, 4 and 6 h or with tumour necrosis factor (TNF) (20 ng/ml) as positive control and assessed for ICAM-1 expression. Incubation with IR plasma resulted in a significant increase from pre-clamp in PMN CD11b expression. A similar trend was seen in endothelial cell ICAM-1 expression following 2 h incubation. These results indicate that reperfusion-induced endothelial dysfunction may be mediated by plasma factors released upon revascularisation which facilitate neutrophil-endothelial interaction through up-regulation of adhesion receptor expression.

Analysis of Variance↗

Recurrent laryngeal nerve dysfunction following carotid endarterectomy.

Recurrent laryngeal nerve dysfunction is a significant complication of carotid endarterectomy and vocal cord paralysis is a major source of morbidity. This study prospectively assessed patients undergoing carotid endarterectomy to determine the nature and frequency of vocal cord damage and attempt to identify avoidable factors. Fifty consecutive patients undergoing carotid endarterectomy for symptomatic disease were studied. A standardized surgical technique was used emphasizing identification of the vagus nerve and minimal disturbance of the surrounding tissues. All patients underwent pre-operative and post-operative (day 2) indirect laryngoscopy and videostroboscopy. Pre-operative assessment found asymptomatic compensated vocal cord paralysis in one patient who had previously had a stroke. Post-operative laryngoscopy revealed asymptomatic impaired vocal cord mobility in three patients (6%) all of whom recovered completely. In addition six patients (12%) developed post-operative hoarseness of whom five have fully recovered. The remaining patient (2%) developed vocal cord paralysis which is permanent to date. This prospective study demonstrates that recurrent laryngeal nerve dysfunction is a common but often transient complication of carotid endarterectomy. The incidence of vocal cord paralysis in this group was less than many of the reported series. This could be due to the technique of minimal dissection which may prevent disturbance of the vagal segmental blood supply. Pre-operative vocal cord assessment is essential in all patients undergoing carotid endarterectomy.

Aged↗

Effects of hypothermia on the function, membrane integrity, and cytoskeletal structure of hepatocytes.

To increase the storage time of livers for transplantation, a better understanding of hypothermia-induced hepatocyte damage is necessary. To this end, we have characterized the effects of hypothermia on long-term function and cytoskeletal organization of hepatocytes cultured in the collagen sandwich configuration, which maintains the expression of liver-specific functions for several weeks. In these studies, cultured hepatocytes (maintained at 37 degrees C for 7 days) were exposed to 4 degrees C in Leibovitz-15 (L15), University of Wisconsin (UW) solution, or L15 supplemented with 2.5 g% polyethylene glycol (PEG) for various time periods followed by a return to normothermia. When L15 medium was used, the long-term albumin secretion rate of cultured hepatocytes was decreased by 50% after 4 h, and by 95% after 24 h of exposure to 4 degrees C. Amorphous precipitates of F-actin and fragmented short microtubules were also observed after 4 and 12 h of hypothermia, respectively. Similar results were obtained when hepatocytes were stored in UW solution. However, in L15 supplemented with PEG, no significant reduction in long-term albumin secretion rates and intact actin and microtubule morphology was observed even after 24 h of exposure to 4 degrees C. The membrane integrity and long-term albumin secretion of hepatocytes stored in the presence of PEG were decreased to approximately 50% only after 48 h of exposure to 4 degrees C. Thus, PEG may be a useful additive in preservation solutions for hepatocytes in hepatocyte-based liver support systems and for intact tissue as well.

Actins↗

Skin closure and the incidence of groin wound infection: a prospective study.

Groin wound infection is a dreaded complication of vascular surgery and may jeopardize an underlying graft. A variety of skin closures have been used and the object of this study was to prospectively determine the relationship between skin closure and wound infection. One hundred fourteen consecutive patients (70 men and 44 women) undergoing bypass surgery with a groin incision (n = 173) were randomly assigned to skin closure with subcuticular Maxon, interrupted nylon, continuous nylon, or clips following a standard two-layer closure of subcutaneous tissue. Fourteen (12%) patients had diabetes and 50 (44%) had digital ulceration and gangrene. Aortofemoral bypass was performed in 25% of the patients and infrainguinal bypass in the remaining 75%. Perioperative wound cultures were obtained before closure. Wounds were inspected and cultures repeated on postoperative days 3, 5, 7, 10, and 14. Infection was defined as a positive culture. Groin wound infection occurred in 3% of the population and graft infection in 0.6%. The type of suture did not influence the incidence of infection. This study failed to demonstrate a significant difference in the incidence of wound infection with the use of different suture materials. We conclude that suture material should be selected on the basis of surgeon preference and costs.

Aged↗

Renal haemodynamics and prostaglandin synthesis in partial unilateral ureteric obstruction.

Haemodynamic changes in partial unilateral ureteric obstruction (PUUO) may be related to altered prostaglandin synthesis. In 12 dogs the left ureter was partially obstructed for 5 weeks. In six dogs the ureter was reimplanted into the bladder and to investigate the effect of this procedure on the contralateral side the other six animals underwent ipsilateral nephroureterectomy. Renal blood flow (RBF) was measured by the distribution of radiolabelled microspheres. Changes in urinary prostaglandin (PG) concentrations were validated by renin activity using angiotensin I. Reduced left RBF during obstruction was associated with increased thromboxane A2 synthesis (P < 0.01). Increased RBF to the non-obstructed side was associated with elevated PGE2 formation (P < 0.05). Elevated angiotensin I levels (P < 0.01) corresponded to maximal increases in PG synthesis. Reimplantation of the obstructed kidney did not exert a direct effect on contralateral RBF or PG concentration. Haemodynamic changes in PUUO in vivo are associated with alterations in renal PGs.

Angiotensin I↗

The comparison of type of incision for transperitoneal abdominal aortic surgery based on postoperative respiratory complications and morbidity.

Equal access to the abdominal aorta can be attained through midline and transverse abdominal incisions. The surgical literature suggests that transverse incisions cause less postoperative pain and morbidity. Fifty patients (10 females and 40 males, mean age 67 years) undergoing abdominal aortic surgery were randomised to a midline (n = 25) or transverse (n = 25) incision. All patients were evaluated preoperatively and postoperatively for seven days. Changes in pulmonary function (FVC and FEV1), time to open and close the incision, analgesia used (morphine mg/kg/h), clinical or X-ray evidence of chest infection, and the duration of ICU stay were recorded. In the transverse group there was a reduction in the incidence of chest complications (20% vs. 28%, p = ns) and these incisions took longer to open (13.9 +/- 4.6 vs. 9.9 +/- 5.1, p < 0.05), but overall there was no significant difference between any other parameter in the two groups. Our results show no statistically significant difference in morbidity or analgesia consumption following transverse or midline abdominal incisions and we conclude that the type of incision used can be left to the surgeon's preference.

Aged↗

Is antibiotic penetration compromised in the ischaemic tissues of patients undergoing amputation?

Antibiotic prophylaxis is indicated for patients undergoing amputation for severe ischaemia or gangrene. However, the adequacy of tissue levels of antibiotics in ischaemic tissue is not known. In this study the serum and tissue antibiotic levels were measured after intravenous administration of metronidazole (15 mg/kg body weight) and cephradine (20 mg/kg body weight). In 11 patients, venous samples were taken at time 0 (induction of anaesthesia) 10, 30 and 60 min. Samples of 2 g each of fat and muscle were collected from the amputation site and three distal sites. Metronidazole and cephradine levels were measured and the degree of limb ischaemia estimated preoperatively by an isotope limb blood flow method. Our results indicate that both metronidazole and cephradine penetrate ischaemic tissues to levels equivalent of a Mean Inhibitory Concentration (MIC) 50 for most organisms encountered in vascular surgery, and that the degree of ischaemia does not alter this.

Aged↗

Effect of preclotting on the porosity and thrombogenicity of knitted Dacron grafts.

The effects of single- and four-stage preclotting methods on graft porosity and thrombogenicity were compared in two types of Dacron prosthesis. The single-stage method significantly reduced leakage of blood (P less than 0.001), but did not seal the grafts. The four-stage method rendered the grafts impermeable at the second step. Thrombogenicity was compared by perfusing preclotted grafts with fresh heparinized blood (containing 111In-labelled platelets) in an artificial circulation. Platelet deposition and consumption were significantly less in the four-stage method whilst platelet function remained unchanged during perfusion. We conclude that the four-stage technique is superior to standard preclotting methods by rendering knitted Dacron grafts impermeable and hypothrombogenic.

Blood Coagulation↗

The effect of indobufen on the thrombogenic potential of a Dacron prosthesis in an artificial circulation.

We have evaluated the effect of indobufen on the potential thrombogenicity of a Dacron vascular prosthesis in an artificial circulation. In a randomised double blind crossover study, ten healthy volunteers received indobufen 200 mg or placebo twice daily for one week. The artificial circulation, incorporating a 15 cm length of 8 mm Dacron graft was perfused for 60 mins with volunteer blood containing autologous 111In labelled platelets. Graft thrombogenicity was assessed by changes in platelet function, isotope labelled platelet studies and scanning electron microscopy. Platelet count fell significantly during graft perfusion (P less than 0.05) and aggregation was significantly inhibited by treatment with indobufen pre perfusion compared with the placebo group (P less than 0.02). While deposition of labelled platelets was not statistically significant, consumption of these platelets was greater in the placebo group (P less than 0.01). Field counts of adherent platelets made from scanning electron micrographs of the indobufen treated group were significantly lower (P less than 0.01) compared with the placebo group. We conclude that indobufen can reduce the thrombogenic potential of Dacron vascular grafts and suggest that it may be an effective antiplatelet agent for use following Dacron bypass surgery.

Blood Vessel Prosthesis↗