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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 109 records · Page 6Linked to original sources
PubMed1997

Assessment of human long saphenous vein function with minimally invasive harvesting with the Mayo stripper.

BACKGROUND: The use of the Mayo Stripper to harvest the long saphenous vein has been shown to improve morbidity from leg wound incisions. It has not been universally accepted because of a perceived increase in injury to the venous conduit. OBJECTIVE: To compare the function of undistended autologous long saphenous vein harvested by a Mayo stripper with the traditional 'open' technique in the same patient (n = 12) appearance. METHODS: Vascular reactivity was assessed in isolated organ baths. Contractile function was measured in response to increasing concentrations (10(-9)-10(-5) mol) of 5-hydroxytryptamine and noradrenaline. This was calculated as a percentage of the maximum contractile response to 90 mM KCl measured in millinewtons (mN) (control 41.4 +/- 12.1, (n = 11), open technique 35.8 +/- 11.1, (n = 11), Mayo stripper 33.7 +/- 15.9, (n = 11)). The endothelial dependent and independent function was assessed with acetylcholine and sodium nitroprusside, respectively. RESULTS: There was no significant difference in response to both constrictors and dilators between vein taken with the Mayo stripper compared with the traditional open technique (n = 6 for each observation; P > 0.05 by ANOVA). Histological examination by light microscopy of the vessel segments removed with the Mayo stripper was unable to show any significant damage to the vessel wall. Both functional and morphological studies were conducted by 'blinded' observers. One-year follow-up with magnetic resonance angiography (MRA) and stress thallium tomography demonstrated a patency rate with lower and upper estimates of 80 and 94%. CONCLUSIONS: We have shown that harvesting the long saphenous vein with a Mayo stripper does not compromise vascular reactivity of the long saphenous vein or long-term patency.

Analysis of Variance↗
PubMed1997

Defective antigen presentation by lavage cells from terminal patients with cystic fibrosis.

Macrophages separated from lavage samples obtained from lungs removed at transplantation from patients with cystic fibrosis (CF) and other lung diseases, have been compared with circulating monocytes from the same patients for their ability to stimulate allogeneic normal circulating lymphocytes and to present antigen to autologous hilar lymph node cells. In general, macrophages separated from lavage samples from CF patients were unable to stimulate allogeneic lymphocytes and to present antigen, although monocytes from the same patients were functional in both assays. In contrast, lavage cells from non-CF patients were generally effective in both allogeneic stimulation and antigen presentation. These data suggest that immune cells within the lungs of CF patients are functionally compromised, a deficiency which may contribute to the recurrent infections characteristic of the disease.

Antigen Presentation↗
PubMed1997

The prognostic significance of non-invasive cardiac tests in heart transplant recipients.

The long-term mortality and morbidity of cardiac transplant recipients is related to their subsequent development of accelerated coronary atheroma and its complications. Coronary angiography was compared with non-invasive clinical assessment to see which was better in predicting clinical outcome. Ninety-one consecutive transplant recipients (mean age 53 years), in whom investigations had been performed (exercise electrocardiography, rest and exercise radionuclide ventriculography, 2-D echocardiography and coronary angiography), were followed up for a mean period of 2.1 years. Eighteen patients had 31 cardiac events. There were five cardiac-related deaths, 17 myocardial infarctions and/or onsets of heart failure, eight percutaneous transluminal coronary angioplasties and one coronary artery bypass graft. With cardiac event-free survival as the dependent variable and the results of the above investigations as independent variables, a series of univariate, bivariate and regression analyses were performed. On bivariate analysis, an echocardiographic ejection fraction of > 60% significantly predicted both survival free of myocardial infarction and/or heart failure and/or cardiac death and survival free of any cardiac event (P = 0.001 for both). Absence of coronary angiographic disease (both of < 25% and of < 50% luminal narrowing in any vessel) significantly predicted survival free of any cardiac event (P = 0.00004 and 0.015, respectively). Neither radionuclide ventriculography nor exercise electrocardiography were significant predictors of event free survival. In conclusion, echocardiography is at least as important as coronary angiography in the follow-up and prognostic assessment of cardiac transplant recipients.

Cause of Death↗
PubMed1997

An evaluation of nebulized prostacyclin in patients with primary and secondary pulmonary hypertension.

AIMS: To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. METHODS AND RESULTS: Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81.min-1 of oxygen and administered in doses increasing from 15 to 50 ng.kg-1.min-1 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 ng.kg-1.min-1 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56 +/- 5 to 45 +/- 4 mmHg (P = 0.0001). The pulmonary vascular resistance decreased by 38% from 964 +/- 169 to 595 +/- 116 dyne.s-1.cm-5 (P = 0.0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. CONCLUSION: Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertensions.

Administration, Inhalation↗
PubMed1997

Activation of coagulation and platelets is affected by the hydrophobicity of artificial surfaces.

Clot formation is a limiting factor in the use of biomaterials. We investigated the effect of surface hydrophobicity on haemostatic activation in vitro, using five polyetherurethanes of varying surface hydrophobicity (C94, C74, C54 and C34), C94 the most, and C34, the least hydrophobic, and compared them with a commercial standard pellethane. Sterilised sacks were filled with heparinised blood, rotated at 37 degrees C for 24 h and sequential samples collected into 0.103 M sodium citrate. Thrombin generation measured by thrombin-antithrombin III complexes showed a difference between the polymers at 3 h through to 6 h (P < 0.05), C94 showing the least activation and C34 the most. Factor XIIa and D-dimer levels increased between 12 (P < 0.05) and 24 h (P < 0.01) for all polyetherurethanes. The ratio of soft:hard segments (which determine hydrophobicity) of the polyetherurethanes showed a direct relationship with the degree of activation of coagulation and fibrinolysis. There was no significant increase in monocyte tissue factor expression at 5 and 105 min. Platelet function as measured by whole blood platelet aggregation showed a reduction with pellethane and C94 after 1 h using collagen, with no changes for C34, Altering surface hydrophobicity has diverse effects on haemostatic pathways, with the most hydrophobic surfaces causing least activation of coagulation but most activation of platelets.

Adult↗
PubMed1997

Activation of naive xenogeneic but not allogeneic endothelial cells by human naive neutrophils: a potential occult barrier to xenotransplantation.

Here we demonstrate that human neutrophils, the predominant circulating leukocytes in intimate contact with endothelial cells lining the vasculature, directly recognize xenogeneic endothelium independently of xenoreactive natural antibody and complement. A rapid and calcium-dependent activation of native (unstimulated) xenogenic endothelial cells by human neutrophils leads to 1) translocation of P-selectin from the Wiebel-Palade bodies to the surface of xenogeneic endothelial cells, 2) increased synthesis and expression of vascular cell adhesion molecule-1 on the xenogeneic endothelial cells, and 3) enhanced killing of the xenogeneic endothelium by natural killer cells. Our data directly implicate naive neutrophils as major early participants in xenograft recognition and endothelial activation independent of xenoreactive natural antibodies and complement.

Animals↗
PubMed1997

[Neoadjuvant chemotherapy in the treatment of breast cancer. Results and prospectives].

Preoperative chemotherapy for breast cancer has been originally proposed in the treatment of locally advanced tumors (T3b-T4) in order to allow radiotherapy or radical mastectomy. Later, it has been employed also for less advanced stages of the disease (T2-T3), to allow conservative surgery. Personal series of 45 patients that underwent preoperative chemotherapy (FAC) for breast cancer stages T2-T3 is reported. A partial response in terms of reduction of tumor volume was obtained in 80% of these patients, a complete response in 6.6% of the cases. In 48.8% a quadrantectomy has been performed, as the lesion diameter was < 2.5 cm after chemotherapy. The survival rate was 70% at 10 years, and 80% for initially T2 tumors, compared with 50% 10 year survival rate in a group of patients with T2 tumors treated before the introduction of neoadjuvant chemotherapy at our Department. Neoadjuvant chemotherapy allows reduction of the initial volume of breast cancer and performance of conservative instead or radical surgery, with better cosmetic results. Moreover these data suggest that they may improve the plateau of the survival curve of patients with locally advanced breast cancer.

Breast Neoplasms↗
PubMed1996

Isolation, culture, and characterisation of MHC class II-positive microvascular endothelial cells from the human heart.

Immunological studies of human endothelial cells have been performed almost entirely on endothelial cells (EC) derived from foetal (umbilical vein) or adult (aorta) large vessels. Immunologically these EC have in common the fact that they are negative for major histocompatibility complex (MHC) class II antigens (HLA-DR), in contrast to microvascular cells within the heart which are constitutively positive for HLA-DR antigens. Here we describe a simple method for isolating microvascular EC from chunks of adult human ventricle using antibody (anti-HLA-DR) or Ulex lectin-coated magnetic beads. Cytospins of primary isolates reveal the majority of cells binding the beads are CD31+ve, CD36+ve, and HLA-DR+ve. After 14 weeks in culture, 19% of cells remained HLA-DR+ve but CD36 expression had disappeared. Cultures after 4-7 passages were analysed by flow cytometry and immunocytochemical staining of cytospins with mAbs against conventional endothelial antigens (EN4, PECAM-1, vWF, uptake of acetylated LDL) and nonendothelial antigens (CD45, cytokeratin, alpha-actin, desmin, MHC class I and class II). The observation that all the cells remained positive for CD31 and did stain strongly for cytokeratin confirmed their endothelial origin. There was some persistent, albeit low level, expression of HLA-DR which was upregulated by interferon-gamma, showing kinetics of induction similar to that found on large vessel EC. These microvascular cells should be very useful for those wishing to compare microvascular with macrovascular EC and for immunological studies of heart endothelial cells.

Adult↗
PubMed1996

Binding of [3H]-5-hydroxytryptamine to human coronary artery and bypass graft vessels.

OBJECTIVES: 5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS: Epicardial coronary arteries obtained from patients undergoing cardiac transplantation, internal mammary arteries from heart donors and saphenous veins from patients undergoing coronary bypass surgery, were sectioned and incubated with [3H]-5-HT for in vitro receptor autoradiography. RESULTS: Microscopic analysis of high resolution autoradiographic images revealed a similar pattern of [3H]-5-HT binding in epicardial coronary and internal mammary artery, where it predominated in the lamina muscularis. In the saphenous vein, binding increased towards the adventitia which showed dense, displaceable binding to the vasa vasorum as well as to nerve-like structures, from which binding was only partially displaced. Computer-assisted densitometric analysis of low resolution autoradiographs revealed a high degree of specific binding to all vessels examined. CONCLUSIONS: The distribution of the [3H]-5-HT binding is different in the saphenous vein compared to epicardial coronary and internal mammary artery. The dense binding to vasa vasorum in the saphenous vein suggests a role for 5-HT in closure of these nutrient vessels, which could contribute to the formation of atherosclerotic changes in saphenous vein grafts.

Adult↗
PubMed1996

Influence of cooling on mesenteric vascular reactivity.

OBJECTIVES: Cardiopulmonary bypass has been shown to cause hypoperfusion of certain vascular beds leading to multiple system organ failure. It has been reported that the gut may be an important trigger. The underlying mechanism is not fully known, but vascular changes, particularly those due to cooling, could play a role. METHODS: We examined the effect of cooling (28 degrees C) and subsequent rewarming (37 degrees C) on the vascular reactivity of the rabbit mesenteric artery and abdominal aorta to a range of vasoactive substances using an in vitro organ bath apparatus. Cumulative concentration-responses of the agonists (noradrenaline, histamine, dopamine and potassium chloride) were examined at 37 degrees C, then repeated at 28 degrees C and then subsequently repeated after rewarming to 37 degrees C. RESULTS: All agonists were capable of inducing a constrictor response on the mesenteric artery and abdominal aorta. The results represent means +/- SEM. There was an increase in potency of noradrenaline at the lower temperature [from 5.6 +/- 0.1 (37 degrees C) to 6.0 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 10], which returned to normal [5.6 +/- 0.1 (37 degrees C)] following rewarming in the mesenteric artery. In contrast, there was a decrease in potency of noradrenaline in the aorta on cooling [6.5 +/- 0.1 (37 degrees C) to 6.2 +/- 0.1 (28 degrees C); Bonferroni-corrected P < 0.05; n = 8]. Neither histamine or dopamine showed any difference in potency at 28 degrees C or at 37 degrees C following rewarming in the mesenteric artery or aorta. There was no difference in the efficacy of the response of the mesenteric artery to noradrenaline as indicated by the maximum responses. However, the response to the highest dose of dopamine was increased on rewarming to 37 degrees C compared to control responses at 37 degrees C before cooling in the aorta [7.23 +/- 1.48 g vs 3.6 +/- 0.6 g; Bonferroni-corrected P < 0.05; n = 14]. Histamine contractions were attenuated at 28 degrees C and following rewarming to 37 degrees C in the mesenteric artery [5.5 +/- 0.5 g (37 degrees C) vs 2.2 +/- 0.2 g (28 degrees C); Bonferroni-corrected P < 0.05; n = 18], [5.5 +/- 0.5 g (37 degrees C) vs 2.32 +/- 0.5 g (37 degrees C rewarming); Bonferroni-corrected P < 0.05; n = 18]. CONCLUSIONS: We conclude that cooling elicits a heterogeneous responsiveness of the rabbit mesenteric artery and abdominal aorta to noradrenaline and dopamine which could have important implications for blood flow to mesenteric vascular beds during hypothermic cardiopulmonary bypass.

Adrenergic alpha-Agonists↗
PubMed1996

Transmission of donor Epstein-Barr virus (EBV) in transplanted organs causes lymphoproliferative disease in EBV-seronegative recipients.

Epstein-Barr virus (EBV) is associated with post-transplant lymphoproliferative disease (PTLD). To determine whether the donor EBV isolate is transmitted to the recipient via the allograft and causes PTLD, EBV isolates from four cases of PTLD in cadaveric heart and/or lung transplant recipients were compared with the donor isolates by PCR and DNA sequence analysis. Two recipients who were EBV seronegative at transplantation acquired an EBV isolate indistinguishable from that of the donor and developed PTLD. In contrast, in two patients who were seropositive before transplantation, the donor isolate differed from that present in PTLD of the recipient. The results suggest that the acquisition of donor EBV is a risk factor for PTLD development in a previously seronegative transplant recipient.

Adolescent↗
PubMed1996

The place of perceived exertion ratings in exercise prescription for cardiac transplant patients before and after training.

OBJECTIVE: Heart rate provides a poor guide to exercise prescription after cardiac transplantation. This study explores whether the rating of perceived exertion (RPE) provides useful alternative information. METHODS: Borg's original categoric scale was applied to 36 male patients [T, age 47(SD 9 years] as they performed a progressive cycle ergometer test an average of seven months (range two to 23 months) after cardiac transplantation. The test was repeated after 16(7) months of progressive exercise centred rehabilitation. Sedentary but healthy controls [C, n = 45, age 45(7) years] performed a similar progressive cycle test. RESULTS: Initially, 13 RPE units corresponded to 66(12)% of peak VO2 in T and 50(11)% in C. Rehabilitation augmented peak VO2 (by 19%) and estimated lean body mass (by 3.5%) in the cardiac transplant patients. The increase of heart rate (HR) at 13 RPE units [delta HR = 10(17) beats.min-1] showed moderate correlations with gains of lean mass (r = 0.72) and gains of peak VO2 (r = 0.58). The relative oxygen intake at 13 RPE units remained unchanged at 68(12)% of peak VO2. CONCLUSIONS: Large inter-individual variations of RPE at a given VO2 limit the value of perceived exertion in exercise prescription. Ratings seem best restricted to fine tuning fixed distance/fixed speed exercise prescriptions in patients undergoing rehabilitation after cardiac transplantation.

Adult↗
PubMed1996

Vulnerability of paediatric myocardium to cardiac surgery.

OBJECTIVE: Myocardial injury is an important cause of mortality and morbidity after paediatric cardiac surgery. Data obtained from studies in animals imply that juvenile myocardium is more resistant to the effects of ischaemia and reperfusion than adult myocardium but there is little confirmatory evidence in the clinical setting. DESIGN: Prospective observational study of biochemical markers of myocardial injury in a paediatric population undergoing cardiac surgery. SETTING: Tertiary referral centre for paediatric cardiac surgery. PATIENTS: Forty patients undergoing paediatric cardiac surgery of varying complexity including closure of atrial and ventricular septal defects and arterial switch for simple transposition. A control group included patients undergoing thoracotomy for closure of a patent ductus arteriosus or repair of a coarctation. INTERVENTIONS: Serial measurements of myoglobin, the MB isoenzyme of creatine kinase (CK-MB), and the highly specific markers of myocardial damage cardiac troponin T (cTnT) and I (cTnI) were made before and 1, 6, 24, and 48 to 72 hours after operation. RESULTS: There were significant increases in myoglobin and CK-MB, but not cTnT or cTnI, in the control group. There were significant increases in the four biochemical markers in all the cardiac operations but especially in the ventricular septal defect and transposition group. Increases in CK-MB and cTnT were about five times greater than those previously reported in adult patients. CONCLUSIONS: (i) Cardiac troponins are more specific markers of myocardial injury in paediatric cardiac surgery than myoglobin and CK-MB. (ii) Paediatric myocardium seems to be more vulnerable to injury during cardiac surgery than adult myocardium.

Adult↗
PubMed1996

Intraoperative apical ventricular septal defect closure using a modified Rashkind double umbrella.

OBJECTIVE: To demonstrate the safety and efficacy of intraoperative apical ventricular septal defect (VSD) closure using a modified Rashkind double umbrella. DESIGN: Descriptive study of all patients in whom intraoperative device closure of apical VSDs was attempted. SETTING: A tertiary referral centre. PATIENTS: Four patients with an apical VSD requiring closure, during the period January 1993 to May 1995. INTERVENTIONS: Intraoperative placement of a modified Rashkind umbrella. RESULTS: Four successful placements resulting in apical VSD closure, as judged by transoesophageal colour flow mapping. Three patients received a 17 mm and one a 12 mm umbrella. Early complete closure was achieved in three patients. There was a small residual leak around the 12 mm device that had resolved at 5 month follow up. There was one early death, which was unrelated to VSD closure. CONCLUSION: Apical ventricular septal defects can be closed safely and effectively with intraoperative use of a modified Rashkind umbrella.

Adult↗
PubMed1996

[Eikenella corrodens pleuro-pulmonary infection. Apropos of a case].

A case of single bacteria pleuropulmonary infection was observed in a 21-year-old patient with heterozygous sicle-cell amenia. The role of this bacteria in pleuropulmonary suppuration, the pathophysiology and secondary lesions are discussed together with therapeutic modalities.

Adult↗