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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 37 records · Page 2Linked to original sources
PubMed2002

Multi-vessel off-pump coronary artery bypass grafting can be taught to trainee surgeons.

BACKGROUND: Although, Off-Pump Coronary Artery Bypass (OPCAB) surgery is being increasingly explored and practised in many cardiac units worldwide, there have been only few reports documenting the training of surgeons in this new technique. The purpose of this study was to address the reproducibility of the OPCAB in a unit where this technique is used extensively. METHODS: Registry data, notes and charts of 64 patients who were operated on by four trainee cardiac surgeons over a period of thirteen months at Harefield Hospital, were reviewed retrospectively. These trainees were part of an accredited training programme for cardiothoracic training and were trained by a single consultant trainer in a cardiac unit after it has had an established recent experience in performing non-selective OPCAB for all coming-in patients. Five (7.8%) patients (with 17 distal anastomoses) consented and underwent early postoperative angiography to check the quality of the grafts and anastomoses. RESULTS: The mean age of the study patients was 65.6 and the mean Parsonnet score was 9.4. There was a mean of 2.9 grafts per patient and circumflex territory anastomoses were performed in 48 (75%) patients. No operation required conversion to Cardiopulmonary Bypass (CPB). Angiography of the five patients revealed satisfactory seventeen (100%) distal anastomoses. CONCLUSION: With appropriate training, it is possible for trainees to learn OPCAB and perform multi-vessel revascularization in relatively high-risk patients with good results.

Adult↗
PubMed2001

Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections.

BACKGROUND: The coxsackievirus and adenovirus receptor (CAR) was identified as a common cellular receptor for both viruses, but its biological and pathogenic relevance is uncertain. Knowledge of CAR localization in the human cardiovascular system is limited but important with respect to CAR-dependent viral infections and gene transfer using CAR-dependent viral vectors. METHODS AND RESULTS: Explanted failing hearts from 13 patients (8 with dilated cardiomyopathy [DCM] and 5 with other heart diseases [non-DCM]) and normal donor hearts (n=7) were investigated for the expression levels and subcellular localization of CAR and the adenovirus coreceptors alpha(v)beta(3) and alpha(v)beta(5) integrins. CAR immunoreactivity was very low in normal and non-DCM hearts, whereas strong CAR signals occurred at the intercalated discs and sarcolemma in 5 of the 8 DCM hearts (62.5%); these strong signals colocalized with both integrins. In all hearts, CAR was detectable in subendothelial layers of the vessel wall, but not on the luminal endothelial surface, and on interstitial cells. Human CAR (hCAR) expressed in rat cardiomyocytes was targeted to cell-cell contacts, which resembled CAR localization in DCM hearts and resulted in 15-fold increased adenovirus uptake. CONCLUSIONS: Low hCAR abundance may render normal human myocardium resistant to CAR-dependent viruses, whereas re-expression of hCAR, such as that observed in DCM, may be a key determinant of cardiac susceptibility to viral infections. Asymmetric expression of hCAR in the vessel wall may be an important determinant of adenovirus tropism in humans. hCAR subcellular localization in human myocardium and hCAR targeting to cell-cell contacts in cardiomyocyte cultures suggest that hCAR may play a role in cell-cell contact formation.

Adenoviridae↗
PubMed2001

Returning to school after heart or heart-lung transplantation: how well do children adjust?

BACKGROUND: Up to 40% of children and adolescents with chronic illness experience school-related problems, including learning difficulties and problems in social adjustment and peer relationships. Despite the life-threatening nature of heart and heart-lung transplantation and the severity of illness, which results in the necessity for surgery, there is little information on the school performance of children after transplantation. METHODS: Eighty-one children and adolescents were assessed with regard to their academic attainments and behavior at school at regular intervals after heart (n=47) or heart-lung (n=34) transplantation and comparisons made with a group of healthy children. RESULTS: Cognitive ability and performance on academic attainments were within the normal range and did not change significantly as a function of time since transplant. However, performance was at a significantly lower level than that of the healthy children. Although the prevalence of behavior problems was only 8% at 6 months posttransplant, at 3 years, it had increased to 29% and, at 5 years, it was still 27%. Children with an initial diagnosis of congenital heart disease had more academic and behavioral difficulties than those with either cardiomyopathy or cystic fibrosis. CONCLUSIONS: A significant number of children who had undergone successful transplantation experienced difficulties at school. Contrary to expectations, educational problems were more prevalent in the medium term, rather than short term, after transplant. Initial diagnosis was a salient factor in posttransplant psychological functioning at school. Early intervention and close liaison with schools is indicated to reduce psychological morbidity and enhance adaptation within the school environment.

Absenteeism↗
PubMed2001

Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis.

Pulmonary arteries of patients with severe pulmonary hypertension (SPH) presenting in an idiopathic form (primary PH-PPH) or associated with congenital heart malformations or collagen vascular diseases show plexiform lesions. It is postulated that in lungs with SPH, endothelial cells in plexiform lesions express genes encoding for proteins involved in angiogenesis, in particular, vascular endothelial growth factor (VEGF) and those involved in VEGF receptor-2 (VEGFR-2) signalling. On immunohistochemistry and in situ hybridization, endothelial cells in the plexiform lesions expressed VEGF mRNA and protein and overexpressed the mRNA and protein of VEGFR-2, and the transcription factor subunits HIF-1alpha and HIF-1beta of hypoxia inducible factor, which are responsible for the hypoxia-dependent induction of VEGF. When compared with normal lungs, SPH lungs showed decreased expression of the kinases PI3 kinase and src, which, together with Akt, relay the signal transduction downstream of VEGFR-2. Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMed2001

Effects of cross-linking ICAM-1 on the surface of human vascular smooth muscle cells: induction of VCAM-1 but no proliferation.

OBJECTIVE: Intercellular adhesion molecule (ICAM)-1 is an immunoglobulin-like cell adhesion molecule expressed by several cell types, including proliferating vascular smooth muscle cells (VSMC). Cross-linking ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activation within the cytoplasm. Here, our objective was to examine events following ligation of ICAM-1 on the surface of human VSMC. METHODS: VSMC were isolated by explant from human pulmonary arteries or aortic tissue from cardiac transplant donors. ICAM-1 was ligated with monoclonal antibodies, followed by cross-linking with a secondary antibody. Activation of signalling pathways, proliferation and expression of a second adhesion molecule, vascular cell adhesion molecule (VCAM)-1 were investigated. RESULTS: ICAM-1 cross-linking caused an increase in activation of extracellular regulated kinase (Erk)-1/-2 and Jun N-terminal kinase (JNK)-1/-2. mRNA and protein for VCAM-1 was observed after ICAM-1 cross-linking, and this was abrogated by addition of an upstream inhibitor of Erk-1/-2, PD98059. No increase in cell proliferation was observed. CONCLUSIONS: Ligation of ICAM-1 on the surface of vascular smooth muscle cells in vitro, leads to the expression of adhesion molecules associated with monocyte infiltration, but does not contribute to smooth muscle cell proliferation. In vivo, this might lead to prolongation of the inflammatory response within diseased blood vessels, by arresting monocytes within atherosclerotic plaques.

Cell Communication↗
PubMed2001

Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy after cardiac transplantation.

Transplant associated coronary disease (TxCAD) is the main cause of late graft loss following cardiac transplantation. It is a multifactorial disease with immunologic and nonimmunologic components involved. This study was undertaken to analyze the gene polymorphism in adhesion molecules in donors and recipients and to investigate its potential association with the development of TxCAD. A total of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were selected on the basis of the development of TxCAD: patients who had developed TxCAD within 2 years after transplantation, and patients who did not have TxCAD within 4.5-5 years after transplantation. All recipients received CyA and azathioprine as a primary immunosuppression. Associations were assessed by using Fisher's exact test. No association was found between E-selectin, L-selectin, and PECAM allele or genotype frequencies and TxCAD. However, the donors whose recipients did not develop TxCAD at first 2 years had a significant increase of ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8% vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we found that the decreased frequency of ICAM E469 allele was associated with the increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1, which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our data suggest the presence of allele E469 ICAM-1 in either donor or recipient is protective against allograft rejection in a transplant setting.

Coronary Disease↗
PubMed2001

Kawasaki disease with predominant central nervous system involvement.

A 4-year-old female was hospitalized with clinical and electroencephalographic evidence of acute encephalopathy. Five days later the classic signs of Kawasaki disease appeared. The neurologic outcome in this female was poor despite early treatment with immunoglobulin. Like many other vasculitidies, Kawasaki disease can have predominant neurologic symptoms as the initial presentation and during the subsequent evolution of the condition.

Atrophy↗
PubMed2001

[Acute rhabdomyolysis disclosing polymyositis in children].

UNLABELLED: Traumatic and non-traumatic rhabdomyolysis have been mostly reported in adults. Polymyositis rarely leads to rhabdomyolysis. CASE REPORT: We report the case of a 13-year-old girl with rhabdomyolysis. Full recovery was observed after symptomatic treatment. Nine months later she developed polymyositis. CONCLUSION: Long-term follow-up is necessary for rhabdomyolysis, even in those cases with an isolated occurrence caused by viral infection.

Acute Disease↗
PubMed2001

The clinical outcome of off-pump coronary artery bypass surgery in the elderly patients.

OBJECTIVE: There has been a body of evidence showing that off-pump coronary artery bypass (OPCAB) may reduce morbidity and mortality in the elderly patients. We reviewed our experience, retrospectively, on elderly patients aged 75 years and older who were operated on using the OPCAB technique. We compared their outcome to a similar group of elderly patients who were operated on using conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) during the same period of time. METHODS: Registry data and patients' notes and charts were reviewed for 56 consecutive elderly OPCAB patients (age 78.5+/-3.5 years) and 87 consecutive CPB patients (age 77.2+/-2.4 years, P=0.01). Both groups had similar risk factor profiles: Parsonnet score 17.4+/-4.4 (OPCAB) versus 16.6+/-5.2 (CPB), P=0.19. We studied in detail their preoperative and postoperative data in order to compare the outcomes of both techniques. RESULTS: The length of stay in the intensive therapy unit (ITU) was 35.4+/-52.9h for OPCAB patients and 77.6+/-144.9h for CPB patients (P=0.0008). No patient died within 30 days in the OPCAB group, whilst ten (11%) CPB patients (P=0.0066) died within 30 days. The incidence of serious complications (including pulmonary oedema, septicaemia, permanent stroke and renal dysfunction requiring haemofiltration or haemodialysis) was one (2%) in the OPCAB group and 11 (13%) in the CPB group (P=0.028). CPB patients required a significantly higher number ten (12%) of intra-aortic balloon pumps (IABP) inserted compared to only one patient (2%) in the OPCAB group who required IABP insertion (P=0.05). Nine (11%) CPB patients were re-operated on for bleeding compared to no OPCAB patient (0%) needing re-operation, P=0.011. CONCLUSIONS: Although the mean age of the OPCAB group was significantly higher than the CPB group, the OPCAB group showed a significant reduction in postoperative serious morbidity, ITU stay and mortality. We believe that such a conclusion may have some effect on the decision-making and cost-effectiveness when performing coronary bypass surgery on the elderly population.

Age Factors↗
PubMed2001

Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: relevance to the arterial switch operation.

The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.

Animals↗
PubMed2001

Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.

This retrospective study includes 139 infants (74 girls and 65 boys) treated for status epilepticus at two University hospitals in Tunisia between 1990 and 1997. Their mean age was 11 months. The majority of seizures were generalized (74%) and lasted between 30 minutes and 1 hour (70%). The cause of status epilepticus was classified as acute symptomatic in 56, febrile in 57, remote symptomatic in nine, progressive neurologic in 10 and idiopathic in seven. Overall mortality was 15.8% and neurological sequelae were identified in 36% of the cases during the mean follow-up time of 3.5 years. The incidence of significant sequelae was a function of aetiology (especially acute symptomatic causes) and age (under 1 year of age). We conclude that the most frequent causes of infantile status epilepticus in Tunisia were fever and acute symptomatic causes. Status epilepticus among infants is an important public health problem, with significant associated mortality and morbidity. Management of status epilepticus can be improved by more rapid access to appropriate medical care.

Anticonvulsants↗
PubMed2001

[Cerebromeningeal tuberculosis: 15 pediatric cases].

Fifteen patients (9 girls and 6 boys) with different forms of cerebromeningeal tuberculosis (meningitis: 13 cases, tuberculoma: 2 cases) was reported. Their mean age was 6 years (4 months to 14 years). The initial diagnosis was difficult. Half patients had meningism, abnormal mental state and defects signs. The cerebrospinal fluid (CSF) leukocyte count was > 20/mm3, protein > 1 g/l (66%) and glucose < 2.2 mmol/l (80%). BK was isolated in 7 patients. Five patients (33%) died. Major neurological sequelae developed in 5 patients and 5 patients completely recovered. Factors predicting fatal outcome and permanent sequelae were: diagnosis delay, altered level of consciousness, hypotrophy and low glucose level in CSF.

Adolescent↗
PubMed2001

[Guillain-Barre syndrome in children. Report of 39 cases].

The authors report a retrospective study of 39 cases of Guillain-Barré syndrome in children. Including 23 boys and 16 girls. The mean age was 4 years (14 months to 10 years). A history of infection preceded the polyradiculoneuritis in 75% of cases. The mean duration of extensive phase and of the maximum paralysis was 10 days. A severe respiratory involvement was observed in 9 children and cranial nerve paralysis in 8 children. An early raised cerebrospinal fluid protein concentration was found in 95%. Electrodiagnostic studies, performed in 37 patients, showed nerve conduction velocity slowing in all cases. 28 children (73%) recovered clinically, 8 patients (20%) had residual deficits and 3 patients (7%) died.

Child↗
PubMed2000

BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a potentially lethal disorder, because the elevation of the pulmonary arterial pressure may result in right-heart failure. Histologically, the disorder is characterized by proliferation of pulmonary-artery smooth muscle and endothelial cells, by intimal hyperplasia, and by in situ thrombus formation. Heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR-II) gene (BMPR2), of the transforming growth factor beta (TGF-beta) cell-signaling superfamily, have been identified in familial and sporadic cases of PPH. We report the molecular spectrum of BMPR2 mutations in 47 additional families with PPH and in three patients with sporadic PPH. Among the cohort of patients, we have identified 22 novel mutations, including 4 partial deletions, distributed throughout the BMPR2 gene. The majority (58%) of mutations are predicted to lead to a premature termination codon. We have also investigated the functional impact and genotype-phenotype relationships, to elucidate the mechanisms contributing to pathogenesis of this important vascular disease. In vitro expression analysis demonstrated loss of BMPR-II function for a number of the identified mutations. These data support the suggestion that haploinsufficiency represents the common molecular mechanism in PPH. Marked variability of the age at onset of disease was observed both within and between families. Taken together, these studies illustrate the considerable heterogeneity of BMPR2 mutations that cause PPH, and they strongly suggest that additional factors, genetic and/or environmental, may be required for the development of the clinical phenotype.

Adolescent↗