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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

The effect of orthotopic transplantation on total, beta 1- and beta 2-adrenoceptors in the human heart.

1. [125I]-(-)pindolol binding was used to determine beta-adrenoceptor density in homogenate preparations of right ventricular endomyocardial biopsies from 43 non-rejecting patients over the first 13 months following cardiac transplantation. The selective beta 1 subtype antagonist ligand CGP 20712A was used to determine the subtype density in 32 of the patients. Biopsy specimens from 15 donor hearts were used as controls. 2. beta-adrenoceptor density (expressed in terms of fmol mg-1 protein) was increased in the group of transplanted hearts as a whole compared with the donor hearts with respect to total (35 +/- 2 vs 23 +/- 2) and the beta 1 subtype (25 +/- 2 vs 16 +/- 2) whereas the beta 2 subtype and radioligand dissociation constant did not differ. 3. Non-parametric analysis of variance of total receptor density over time revealed significant heterogeneity which appears to be due to a discrete increase in beta-adrenoceptor density during the 4th post operative month. 4. These results indicate that beta-adrenoceptor density is not constant following transplantation. Furthermore, the increase in receptor density following transplantation is due mainly to an increase in the beta 1 subtype without a significant change in the beta 2 subtype.

Adult↗
PubMed1992

Optimized hemodynamics by implantation of a dual chamber pacemaker after heterotopic cardiac transplantation.

A patient who underwent prior heterotopic cardiac transplantation had persistent complaints of dyspnea, palpitations, and fatigue in spite of normal pump function of the donor heart. Repeated Holter monitoring excluded paroxysmal arrhythmias. It was thought that synchronization of both heart rates might alleviate his symptoms. The intrinsic heart rate of the donor heart was 90 beats/min, the recipient heart was 60 beats/min with acceleration up to 130 beats/min on exercise. A DDD pacemaker was implanted, the atrial lead was positioned in the right ventricule of the donor heart and the ventricular lead in the atrium of the recipient heart. Search for an optimal AV interval was evaluated by echo-Doppler and intraarterial pressure recordings. By increasing the AV interval from 125 to 300 msec, the maximum aortic flow velocity of the recipient heart increased from 1.0 to 1.2 m/sec. Left ventricular end-diastolic diameter remained unchanged, left ventricular end-systolic diameter decreased from 52 to 48 mm. Wall motion of the recipient left ventricle improved. At an AV interval of 125 msec there was alternate systolic contraction of both hearts, resulting in arterial pressure waves at a rate of 180/min. This did not relieve his symptoms and he complained further of headaches. At an AV interval of 300 msec contraction of the recipient heart just preceded that of the donor heart, resulting in arterial pressure waves at a rate of 90/min, normalization of the wave form, relief of symptoms, and improvement of exercise tolerance.

Adult↗
PubMed1992

Bioelectric properties of cystic fibrosis airways obtained at heart-lung transplantation.

BACKGROUND: The basic defect in cystic fibrosis centres on abnormal ion transport in affected tissues such as the respiratory tract. Heart-lung transplantation provides a limited supply of native lower airways from these patients. The feasibility of in vitro studies of bioelectric properties and ion fluxes in lower airways, obtained at heart-lung transplantation from patients with cystic fibrosis, has been assessed. Comparison was made with airways from patients without cystic fibrosis. METHODS AND RESULTS: Tissue segments were mounted in Ussing chambers under open circuit conditions. The basal potential difference in tissues from nine patients with cystic fibrosis was -3.6 mV (SE 0.3 mV), not different from tissues from 12 patients without cystic fibrosis of -3.6 mV (0.5 mV). Amiloride (10 microM) caused a significantly greater fall in potential difference in bronchi from patients with cystic fibrosis (83.5% (SE 2.9%)) than in those from controls (55.1% (7.1%)). Isoprenaline (100 microM) produced no significant change in bioelectric properties in non-cystic fibrosis tissues, but induced a 26.2% (6.3%) increase in potential difference in cystic fibrosis airways. The latter response was reduced by amiloride pretreatment. Mucosal chloride substituted Krebs-Henseleit solution caused no change in bioelectric properties in cystic fibrosis airways. Sodium substituted Krebs solution produced a substantial fall in potential difference similar in magnitude to that seen after amiloride. Isotropic flux measurements showed no significant differences between non-cystic fibrosis and cystic fibrosis airways. No net movement of Na+ or Cl- was detected under open circuit conditions in either group. CONCLUSIONS: Cystic fibrosis bronchi obtained at heart-lung transplantation provide a viable source of tissue for in vitro studies of bioelectric properties. The increased response to amiloride characteristic of the upper airways in cystic fibrosis is retained in these tissues, as is the reduced chloride conductance. Although no differences in isotopic fluxes were seen between non-cystic fibrosis and cystic fibrosis tissues, heavily infected airways from patients with cystic fibrosis may not be suitable for ion flux measurements.

Amiloride↗
PubMed1992

Pulmonary endothelial permeability following lung transplantation.

During lung transplantation, a number of factors may cause endothelial injury to the donor organ, including ischemia, inadequate preservation, cardiopulmonary bypass, high potassium concentrations, and reperfusion. In this study, protein accumulation index (PAI) was used to assess pulmonary endothelial permeability (PEP) in ten patients immediately after lung transplantation. Six were studied sequentially every other day for ten days postoperatively. The PAI was also measured using the same technique in a group of 11 normal volunteers. Mean PAI x 10(-3)/min +/- (SEM) for ten patients measured within 36 h of transplantation was 1.27 (0.56) compared with 0.45 (0.08) for the normal group (p = 0.09). No correlation was found between preservation time and PAI following reperfusion. Three episodes of lung rejection were observed in two patients during the first ten postoperative days, during which PAI rose to 2.26 (0.26) compared with 0.73 (0.11) for all other studies in the group (p less than 0.01). We conclude that no increase in PEP could be demonstrated after graft reperfusion following lung transplantation as assessed by PAI in this small group of patients. However, further studies may show the technique to be useful in the detection of subsequent episodes of graft rejection.

Cell Membrane Permeability↗
PubMed1992

Aprotinin and heparin monitoring during cardiopulmonary bypass.

BACKGROUND: When high-dose aprotinin is used during cardiopulmonary bypass, there is a prolongation of the activated coagulation time (ACT), which is used to monitor heparinization. The aim of this study was to provide guidelines for monitoring heparin levels by the ACT if aprotinin is used during cardiopulmonary bypass. METHODS AND RESULTS: Heparinized blood from six healthy controls and nine patients on cardiopulmonary bypass was aliquoted and mixed with various concentrations of aprotinin. ACTs were performed on these samples. Activated partial thromboplastin times (APTT) were performed on the citrated plasma mixed with varying concentrations of heparin and aprotinin from the same control patients. Prothrombin times (PT) were performed on plasmas mixed with aprotinin. Aprotinin produced a dose-related prolongation of ACT and APTT but had no effect on PT. This effect occurred whatever the activating agent and in the absence of heparin. CONCLUSIONS: Aprotinin prolongs the ACT and APTT independently of heparin. If high-dose aprotinin is used during cardiopulmonary bypass, ACTs should be maintained at times > 750 seconds to allow for appropriate levels of heparin.

Aprotinin↗
PubMed1992

Detrimental effects of temperature on the efficacy of the University of Wisconsin solution when used for cardioplegia at moderate hypothermia. Comparison with the St. Thomas Hospital solution at 4 degrees C and 20 degrees C.

BACKGROUND: We have previously reported the superior protective properties of the University of Wisconsin (UW) solution compared with the St. Thomas solution (ST) in the rat heart subjected to the deep hypothermia (4 degrees C), thus demonstrating its possible use in cardiac transplantation. We thought it was important to evaluate the potential of the UW solution as a cardioplegic solution under the moderately hypothermic (20 degrees C) conditions of routine intraoperative myocardial protection. METHODS AND RESULTS: Isolated rat hearts were subjected to 60 minutes of ischemia at 4 degrees C or 30 (or 60) minutes of ischemia at 20 degrees C with UW, ST, and ST plus 100 mM K (ST + 100) solutions. Coronary flow, mechanical function, endothelial function, and ultrastructure were observed. Mean time (seconds) to infuse 10 ml of cardioplegic solution under constant pressure, a measure of coronary vascular resistance at 4 degrees C and 20 degrees C, respectively, for each solution were ST, 69.2 +/- 6.9 and 64.7 +/- 3.8; UW, 142.2 +/- 8.8 and 187.2 +/- 10.0 (p < 0.01); and ST + 100, 78.2 +/- 8.0 and 176 +/- 8.1 (p < 0.001). Mean recovery values of cardiac output (expressed as percentage of its preischemic value) after 60 minutes of ischemia at 4 degrees C were ST, 95.5 +/- 2.1%; UW, 93.0 +/- 2.4%; and ST + 100, 96.5 +/- 1.5%. After 30 minutes of ischemia at 20 degrees C, values were ST, 88.0 +/- 1.3%; UW, 72.2 +/- 3.6% (p < 0.005 versus ST); and ST + 100, 53.3 +/- 1.8% (p < 0.001 versus ST). CONCLUSIONS: The efficacies of UW and severely hyperkalemic cardioplegic solutions are affected by the degree of hypothermia under which they are used. Under moderate hypothermia (20 degrees C), severe hyperkalemia induces a marked increase in coronary vascular resistance that is associated with impaired myocardial protection. These studies discourage the use of UW for routine intraoperative cardioplegic arrest where the degree of hypothermia cannot be readily controlled. The ST solution does not share this constraint.

Adenosine↗
PubMed1992

The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia.

Forty eight patients in postmenopause affected by histologically confirmed endometrial hyperplasia (34 with simplex and 14 with complex forms) were administered Danazol therapy, 400 mg/day for 3 consecutive months. At the end of treatment, regression of the endometrial hyperplasia was histologically ascertained in 46 patients (95.9%) with disappearance of the metrorrhagia. Endometrial atrophy was obtained in 75% of the cases, while secretive (14.7%) or proliferative (6.2%) aspects resulted in the others. Only 2 patients (4.1%) showed persistence of the hyperplastic endometrium. On the basis of this experience, treatment with Danazol appears to be effective and safe with only scarce and transient side effects. This therapy is therefore proposed as a valid alternative to progestogen therapy in cases of postmenopausal endometrial hyperplasia.

Aged↗
PubMed1992

Endothelial dysfunction caused by University of Wisconsin preservation solution in the rat heart. The importance of temperature.

The superiority of the University of Wisconsin solution over routinely used crystalloid cardioplegic solutions for myocardial preservation has been demonstrated in animal studies. We have investigated the effect of the University of Wisconsin solution at different temperatures on endothelial function by examining its influence on 5-hydroxytryptamine- and nitroglycerin-induced increase in coronary flow in the isolated rat heart. Thirty-eight rat hearts were perfused on a modified Langendorff preparation. In the control experiments, there was no significant difference in the percentage increase in coronary flow induced by 5-hydroxytryptamine and nitroglycerin after 30 minutes of perfusion with Krebs-Henseleit buffer (n = 6). Continuous infusion of the University of Wisconsin solution for 30 minutes at 4 degrees C or at 10 degrees C did not alter the 5-hydroxytryptamine or nitroglycerin response. However, infusion at 15 degrees C reduced the 5-hydroxytryptamine-induced vasodilation, while at 20 degrees C the 5-hydroxytryptamine response was converted to vasoconstriction without a significant change in nitroglycerin effect (15 degrees C, 5-hydroxytryptamine, before: 30.2% +/- 1.5%, after: 6.0% +/- 1.0%, nitroglycerin, before: 28.8% +/- 1.3%, after: 31.2% +/- 1.8%; 20 degrees C, 5-hydroxytryptamine, before: 32.2% +/- 2.5%, after: -23.8% +/- 3.6%, nitroglycerin, before: 30.3% +/- 1.9%, after: 33.5% +/- 1.7%). Coronary vascular resistance in the control experiments rose from 55.0 +/- 2.5 cm H2O/ml/gm/min to 58.4 +/- 2.3 cm H2O/ml/gm/min (p = not significant). The increase after University of Wisconsin solution infusion at 4 degrees C and at 10 degrees C was similarly not significant. Coronary vascular resistance increased significantly following infusion of University of Wisconsin solution at 15 degrees C (p < 0.001) or at 20 degrees C (p < 0.01). We conclude that University of Wisconsin solution produces temperature-dependent endothelial dysfunction in the isolated rat heart.

Adenosine↗
PubMed1992

Lung allograft transplantation: indications, preoperative assessment and postoperative management.

In spite of a shortage of available donors, an increasing number of heart-lung transplantations have been performed within the last decade. This procedure, first limited to patients with pulmonary vascular disease, has been successfully extended to patients with end stage lung disease, including cystic fibrosis. More recently, single lung, double-lung and bilateral single lung transplantation have become other therapeutic options. Better selection of patients and donors as well as improvements in surgical techniques and immunosuppression regimens have contributed to the reduction in the high perioperative mortality experienced in the early stages. Moreover, the introduction of daily spirometry and transbronchial lung biopsies have permitted early and reliable diagnosis of opportunistic infection and rejection. The most serious late complication of lung transplantation is obliterative bronchiolitis and further research is urgently required to improve diagnosis and management of this condition.

Graft Rejection↗