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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 163 records · Page 9Linked to original sources

Vasovagal reactions may occur after orthotopic heart transplantation.

OBJECTIVES: This study evaluated the ability of patients to manifest vasovagal reactions after orthotopic heart transplantation. BACKGROUND: Paradoxic stimulation of left ventricular baroreceptors may be the afferent limb of the vasovagal reflex in humans. Orthotopic heart transplantation causes surgical denervation of these receptors and would therefore be expected to abolish the vasovagal reflex. METHODS: To attempt to confirm this hypothesis, 10 patients with orthotopic heart transplantation underwent both head-up tilt testing while resting on a saddle support and testing for parasympathetic innervation of the donor heart before and after atropine infusion. Native and donor heart sinus rates were monitored by using an esophageal pill electrode throughout tilting and during parasympathetic testing. RESULTS: Unexpectedly, seven patients had vasovagal responses at saddle support tilt testing, during which native heart rate decreased by 25 +/- 7 beats/min and mean arterial blood pressure decreased by 55 +/- 9 mm Hg. In three of these patients, there was also a decrease in donor heart rate of 23 +/- 26 beats/min. Parasympathetic testing showed possible evidence of donor heart vagal reinnervation in these patients with donor heart bradycardia during tilt but not in those with vasovagal reactions to tilt without slowing of the donor heart rate. CONCLUSIONS: Vagal efferent reinnervation can occur after orthotopic heart transplantation in humans. However, the absence of such reinnervation in some patients with vasovagal responses to tilt calls into question the role of left ventricular receptors in inducing the vasovagal reaction.

Adolescent↗

Coronary angioplasty in cardiac transplant recipients.

Accelerated coronary artery disease following cardiac transplantation remains an important obstacle to long-term survival and the correct management strategy remains unclear. This observational, prospective study was designed to examine the feasibility of using percutaneous transluminal coronary angioplasty (PTCA) in the treatment of post-transplant coronary disease. Thirteen consecutive patients were selected from the total population of 276 transplant recipients who underwent routine coronary angiography between 1987 and 1990. Selection of patients was on angiographic criteria alone and PTCA was performed to all accessible stenoses with more than 80% luminal narrowing. PTCA was performed using standard angioplasty equipment and procedure as considered appropriate for the individual lesion. A successful PTCA was defined as more than 30% reduction in luminal narrowing and a residual narrowing of less than 50%. Restenosis was defined as a loss of 50% or more of the gain achieved at the time of successful PTCA or more than a 30% increase in narrowing at the site of stenosis. A total of 31 lesions were dilated in this group and a successful result was achieved in 29 of these (93%) and in 12 of the 13 patients. The one patient with failed PTCA underwent later successful coronary artery bypass grafting to complete revascularization. Four of the 13 patients have had two angioplasty procedures, two for restenosis and two for disease progression in other sites. One patient died 15 months after the initial PTCA and the remaining 12 were asymptomatic with good exercise tolerance and ventricular function at a mean of 19 months (range 1-39 months) following first PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Hemostatic changes in heart transplant recipients and their relationship to accelerated coronary sclerosis.

Hemostasis was assessed in 115 steady-state heart transplant recipients (HTRs) and compared with that of 23 age-matched healthy controls and 21 age-matched patients with ischemic heart disease (IHD). Compared with the controls, the HTRs had increased levels of fibrinogen (mean and 95% confidence limits of 4.50 [4.32-4.68] g/L versus 3.47 [3.07-3.87] g/L, P < 0.001), factor VIIC (1.16 [0.98-1.21] IU/ml versus 0.99 [0.89-1.10] IU/ml, P < 0.001), and von Willebrand factor antigen (1.72 [1.58-1.88] IU/ml versus 1.00 [0.80-1.26] IU/ml, P < 0.001). HTRs had increased antithrombin III activity (P = 0.002) and protein C activity (P = 0.002), with a decrease in total protein S levels (P < 0.001) but no change in free protein S levels. Stepwise discriminant analysis of hemostatic variables showed that fibrinogen was the best discriminator of the three groups, classifying 55.6% of HTR, 40% of IHD, and 66.7% of the controls. More marked prothrombotic changes were found in HTRs transplanted for IHD than for other causes; this reached significance for prothrombin (P = 0.048), factor IX (P = 0.003), and poor fibrinolytic activity as measured by euglobulin clot lysis time (P = 0.008). The HTRs with accelerated coronary sclerosis (ACS) tended to have the most prothrombotic changes; this reached significance with factor IX (P = 0.03). In conclusion, HTRs have perturbed hemostasis; the net effects of these changes are prothrombotic. The relationship between prothrombotic changes and ACS merits further studies.

Adult↗

In vitro bioelectric properties of bronchial epithelium from transplanted lungs in recipients with cystic fibrosis.

BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT) for cystic fibrosis (CF) may be affected by the original disease as well as other factors such as prolonged organ ischaemic time, the interruption of bronchial arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro measurement of the bioelectric properties of the bronchial mucosal lining may be an effective means of characterising the mucosal function of the lung allografts in response to pharmacological agents. METHODS--Bronchial mucosal tissues from explanted native lungs of CF and non-CF patients at transplantation were used to assess the possible application of a mini-Ussing chamber. With this technique, the bioelectric responses of bronchial mucosal biopsies from six patients with CF, one patient with congenital heart disease, four with primary pulmonary hypertension, and one with emphysema, all after HLT, were studied. The bioelectric and pharmacological responses of biopsies of bronchial mucosa from patients after HLT were compared with biopsies from non-CF non-HLT subjects. RESULTS--The altered bioelectric properties of CF tissues could be detected by the mini-Ussing chamber technique. The basal bioelectric values and the responses to amiloride and isoprenaline in CF patients were not different from those in non-CF patients two years after HLT. No significant difference in the basal bioelectric properties and responses to amiloride and isoprenaline was found between HLT recipients and non-CF non-HLT subjects. CONCLUSIONS--The mini-Ussing chamber is an effective means of characterising the typical CF bioelectric defect which was not found in the transplanted lungs of CF patients up to two years after HLT. Furthermore, values were unaltered in comparison with non-transplanted lungs, suggesting that bronchial epithelial function is maintained after HLT.

Adolescent↗

Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus.

Primary human adult lung epithelial cells (ALEC) were established in culture using the most distal parts of the lung to avoid the airways. Immunocytochemical peroxidase staining and semiquantitative flow cytometry were used to characterize the cells in conjunction with a panel of monoclonal antibodies (mAb). The cells showed a constitutive expression of major histocompatibility complex (MHC) class I antigens, patchy expression of intercellular adhesion molecule-1 (ICAM-1) and a weak patchy expression of MHC class II antigens (detected using immunocytochemical staining). Incubation of the primary ALEC with interferon-gamma (IFN-gamma) (250 U/ml) stimulated an up-regulation of the expression of these three antigens to varying degrees; expression of MHC class I antigens and ICAM-1 molecules showed an up-regulation at 10 hr after the start of the treatment, reaching a peak at 48 hr, maintaining it for the next 24 hr and then, steadily and progressively, losing it towards the end of the experiment at 96 hr. Expression of HLA-DR showed an up-regulation at 17 hr after the start of the treatment, reaching a peak at 72 hr and maintaining it for the next 24 hr. Cytomegalovirus (CMV) infection of ALEC in culture caused an up-regulation of expression of class I antigens and ICAM-1, but not DR. However, when the infected cells were incubated with IFN-gamma, an up-regulation in the expression of DR took place. Therefore, within the micro-environment of the transplanted lung the presence of cytokines (IFN-gamma) produced by infiltrating activated mononuclear cells, may render the lung epithelial cells capable of acting as antigen-presenting cells, expressing high levels of class I antigens, ICAM-1 and class II antigens, activating CD8 and CD4 cells thus playing a major part in the process of rejection of the lung allograft; themselves becoming a primary target in the process.

Adult↗

The medical management of patients with cystic fibrosis following heart-lung transplantation.

Transplantation for end-stage respiratory failure in cystic fibrosis (CF), with encouraging medium-term results, is now possible. This paper details the postoperative medical treatment required by these patients. The management of 79 patients who underwent heart-lung transplantation is described. Details of intensive care, postoperative care, long-term follow-up, and the problems specific for cystic fibrosis patients are reported. The duration of care in the Intensive Care Unit (ICU) was 1-93 days (median 5 days). Intubation was required for 7 h to 93 days (median 48 h), and 11 patients required haemodiafiltration. High doses of cyclosporin A (mean 22 mg.kg-1 q.d.) were required. Acute rejection was common. There were 133 episodes of infection: bacterial 115, viral 11, and other organisms 7. Grand mal seizures occurred in 10 patients, lymphoproliferative disorders in 4, and obliterative bronchiolitis in 17. The median duration of hospital stay was 32 days. Despite having a multi-system disease, patients with CF can be successfully transplanted, if detailed attention is paid to their complex medical management.

Adult↗

Remodeling of the aortic valve anulus.

Isolated aortic valve regurgitation that results from disease that primarily affects the aortic wall can be repaired by remodeling of the aortic anulus to restore its normal geometry. This involves excision of the aortic wall to within 2 to 3 mm of the leaflet attachments, detachment of the coronary ostia, reshaping of the anulus with the aid of a Dacron graft, and then reimplantation of the coronary arteries. Increases in the surface area of the leaflet that are caused by root dilatation are often present and can be accommodated in the repair procedure. In this study we describe our experience with 10 patients with annuloaortic ectasia who underwent the remodeling procedure at the National Heart Hospital and the Royal Brompton Hospital from 1982 to 1990.

Adult↗

[The "blue rubber bleb nevus" (Bean's syndrome): uncommon cause of gastrointestinal bleeding].

A ten year old boy had six cutaneous angiomas and recurrent rectal bleeding responsible for iron deficiency anemia. Histological examination established the diagnosis of blue rubber bleb naevus syndrome. Endoscopy, arteriography, computed tomography, and angioscintigraphy disclosed additional angiomas in the stomach and rectum and along the blood vessels in the lower limbs. The value of angioscintigraphy for identifying angiomas escaping detection by other means was illustrated in this case. Embolization of the inferior mesenteric artery was successful in preventing further rectal bleeding. Treatment of this disorder remains controversial.

Angiography↗

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗

Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans.

In human airways, there is a prominent neural bronchodilator mechanism which is non-adrenergic. In human tracheal segments, we have demonstrated that this response is mediated entirely by nitric oxide (NO), since an inhibitor of NO synthesis, L-NG-nitroarginine methyl ester (L-NAME) (10(-4) M) abolishes this neural response. Identification of the neurotransmitter of this bronchodilator pathway may now make it possible to study its role in physiological control of airway calibre and in airway disease.

Adolescent↗

Attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus.

A survey was carried out into attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus type 1 (HIV-1) infection associated with clinical situations that would normally have been managed surgically with low operative mortality rates and long median survival times. The survey response rate was 72.4 per cent. In patients with acute valvular insufficiency or with continuing angina despite maximal medical therapy (unstable angina) who were HIV-1 antibody positive, 75.8 and 80.8 per cent, respectively, of surgeons would operate. If the patient had end-stage infection, acquired immune deficiency syndrome (AIDS), 29.7 per cent and 34.7 per cent, respectively, would consider surgical intervention. When asked to perform simple procedures such as open lung biopsy or pleurectomy on a patient with AIDS, more than half of surgeons would operate (52.2 and 65.6 per cent respectively). In patients with operable carcinoma of the lung and asymptomatic HIV-1 infection 52.3 per cent would operate. This fell to 15.0 per cent if the patient had a diagnosis of AIDS. The majority of surgeons (77.2 per cent) felt patients should have an HIV-1 antibody test before operation and this rose to 95.6 per cent if patients were in a high-risk group; 60.2 per cent of surgeons had changed their surgical practice to reduce the risks of blood-borne infection.

Attitude of Health Personnel↗

The ultrastructure of pulmonary arteries and arterioles in emphysema.

The lungs from three cases of pulmonary emphysema obtained at heart-lung transplantation were examined by electron microscopy to determine the origin of intimal longitudinal muscle and the formation of muscular tubes in small pulmonary arteries and arterioles. The earliest change consisted of migration of mature smooth muscle cells from the media of small pulmonary arteries, through gaps in the internal elastic lamina, into the subendothelial space. Most of these cells then adopted a longitudinal orientation, maintained a muscular phenotype, and became enmeshed in a web of elastic fibres. A small minority, immediately subjacent to the endothelium, were orientated circularly and, in some vessels, were enclosed by rudimentary internal and external elastic laminae to form early muscular tubes. Pulmonary arterioles, which are normally devoid of a media, contained several layers of circularly orientated smooth muscle cells, some of which also formed muscular tubes. It is postulated that the limited migration of mature smooth muscle cells seen in states of chronic hypoxia is mediated by a different stimulus from that causing the florid invasion of the intima by immature smooth muscle, with subsequent transformation into myofibroblasts, which characterize plexogenic pulmonary arteriopathy.

Adult↗

Cognitive and behavioural status of paediatric patients 1 year after cardiac or cardiopulmonary transplantation.

Cardiac and cardiopulmonary transplantation are being increasingly used as methods of treatment for children with end-stage heart or lung disease, but little is documented about their psychological adjustment to such procedures. In all, 45 children who had undergone heart or heart-lung transplantation were studied 1 year after operation and compared with 39 children who had undergone bone marrow transplantation, 49 children who had undergone conventional cardiac surgery and 46 normal healthy children. None of the 3 treatment groups differed significantly with respect to developmental, cognitive or behavioural measures, but there were significant differences between the transplant and normal groups in the areas of developmental and cognitive functioning. The initial diagnosis of the transplant patients was found to be an important factor in the postoperative psychological functioning.

Adolescent↗

Acute effects of cyclosporin and cremophor EL on endothelial function and vascular smooth muscle in the isolated rat heart.

We studied the effects of cyclosporin dissolved in the vehicle used as an intravenous preparation, namely, cremophor EL, and cremophor alone on the basal coronary flow plus endothelial function and vascular smooth muscle response by examining their influence on 5-hydroxytryptamine (5-HT) and nitroglycerine (GTN) induced the changes in coronary flow in the isolated rat heart. A total of 72 rat hearts were perfused with a modified Langendorf preparation. There was a 12.8 +/- 3% reduction in the basal coronary flow after 60 minutes of perfusion with the drug-free buffer (p = ns). A dose of 50 ng/ml of cremophor or cyclosporin gave a similar reduction in the flow (cremophor 9.2 +/- 0.7%, cyclosporin 12.7 +/- 2%). However, at higher concentrations cremophor caused dose-dependent coronary vasodilation, while cyclosporin had the opposite effect. The maximum effect after 1000 ng/ml of cyclosporin was a 48.7 +/- 0.6% decrease, and after an equivalent dose of cremophor a 24.8 +/- 2.2% increase in the flow. The vasodilatory response to 5-HT and GTN remained unchanged after 60 minutes of perfusion with the drug-free buffer (5-HT, before 33.3 +/- 2.5%, after 37.7 +/- 4.2%; GTN, before 34.3 +/- 2.5%, after 33.7 +/- 1.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of cardiac or heart-lung transplantation on the quality of life of the paediatric patient.

Despite the increase in the use of heart and heart-lung transplantation as methods of treatment for children with end stage heart or lung disease, there is little documented research about the psychological implications of such procedures or about the effects of transplantation on quality of life. Twenty-eight children were studied before and 3 months after heart or heart-lung transplantation and compared with 28 normal children. Developmental and cognitive function were within the normal range, although performance was at a significantly lower level on a number of parameters compared with the normal group. There were no significant changes in any of the developmental or cognitive parameters after transplantation. Pre-operatively the prevalence of problem behaviour at home was significantly higher in the transplant group compared with the normal group, but there was a significant reduction in the prevalence of problem behaviour following transplantation. Early postoperative findings indicate an improvement in quality of life after heart or heart-lung transplantation but longer term follow-up is now necessary.

Adolescent↗

Preserved left ventricular function during supine exercise in patients after orthotopic cardiac transplantation.

Cardiac denervation may affect cardiovascular responses during exercise in patients after orthotopic cardiac transplantation. In 17 such patients, haemodynamic responses and left ventricular function were examined by radionuclide ventriculography during and after supine exercise, at an average of 17.1 +/- 2.6 months after surgery. Data were also obtained during 'volume loading' brought about by leg elevation before exercise. Results were compared with those of six normal controls. At rest, heart rate was significantly faster among transplant patients than among controls (P less than 0.0003). No significant inter-group differences in changes in cardiovascular parameters were found between the two groups during leg elevation. During exercise, heart rate in transplant patients rose at a significantly slower rate than controls (P = 0.0001), but similar increases in ejection fraction, stroke volume and cardiac output were observed among transplant patients and controls. Decline in heart rate (P = 0.0001), ejection fraction (P = 0.0007) and cardiac output (P = 0.0001) was significantly slower in transplant patients during recovery. Although there were differences in rates of increases in heart rate between transplant patients and controls during supine exercise, there were no inter-group differences in increases in cardiac output and ejection fraction and changes in haemodynamic responses and left ventricular volumes.

Adult↗

The prevalence, course, and characteristics of chronic anemia after heart and lung transplantation.

A retrospective study of the 99 surviving heart and lung transplant (HLT) recipients at one center showed that 31% had significant anemia (hemoglobin less than 100g/L) six months after transplantation. Chronic anemia persisted in 18% of HLT recipients two years posttransplantation. A similar study of 100 heart transplant recipients showed no unexplained anemic patients. The prevalence of anemia after HLT was unrelated to the original diagnosis, immunosuppression, or acute rejection. All HLT recipients appeared to be unduly sensitive to the myelosuppressive effects of azathioprine. Detailed studies in 16 representative patients showed a normochromic, anisocytotic anemia with normal reticulocyte counts, B12 and folate levels, and haptoglobin levels and appropriate erythropoietin levels--but increased ESRs, low/normal iron levels and low/normal total iron binding capacity, normal or raised ferritin levels, and autoantibodies in 4 (25%). Bone marrow aspirates in 10 patients showed dyshemopoiesis out of proportion to the degree of anemia and colonies of activated lymphoid cells. The cause for this anemia appears to be a combination of anemia of chronic disease and dyshemopoiesis, both of uncertain etiology.

Adult↗