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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 127 records · Page 7Linked to original sources
PubMed1995

Nitric oxide synthase activity is elevated in inflammatory lung disease in humans.

We have characterised nitric oxide (NO) synthase activity in lung samples from patients with inflammatory lung disease compared to that in normal donor lung. NO synthase activity was measured by the ability of tissue homogenates to convert L-arginine to L-citrulline. Higher levels of NO synthase activity were found in samples from patients with inflammatory lung disease (mild asthma, cystic fibrosis, obliterative bronchiolitis after lung transplantation) compared to samples from healthy donors. NO synthase activity in all samples was mainly dependent on the presence of extracellular Ca2+. The increased NO synthase activity in diseased-lung samples suggests a modulatory role for nitric oxide in lung inflammation.

Adolescent↗
PubMed1995

A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients.

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, Cmax, Cmin and tmax) showed that there were no significant differences between the two formulations except for the tmax, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.

Administration, Oral↗
PubMed1995

Fourteen-year experience with homovital homografts for aortic valve replacement.

Two hundred seventy-five unprocessed, viable homograft ("homovital") aortic valves were used for aortic valve replacement in patients aged 1.5 to 79 years (mean 45.8 +/- 19 years) with maximum follow-up of a 14-year period (mean 4.8 years). Ninety-two percent (252 patients) had New York Heart Association class III or IV functional status before operation and 25 underwent emergency operation. Valves were harvested under sterile conditions and kept in nutrient medium 199. Freehand (subcoronary) technique was used in 147 patients and freestanding root replacement was used in 128. Cumulative survival rates for the whole group were 92% +/- 2% at 5 years and 85% +/- 3% at 10 years, as compared with 96% +/- 2% and 94% +/- 4%, respectively, for the 98 patients who underwent isolated root replacement. Multivariate analysis determined that root replacement with associated procedures and operation for prosthetic endocarditis were risk factors for death, whereas previous xenograft valve, operation for endocarditis, and operation for aortic regurgitation were risk factors for reoperation. Actuarial rates for freedom from degenerative valve failure diagnosed at operation, by postmortem examination, or by routine echocardiography were 94% +/- 2% at 5 years and 89% +/- 3% at 10 years. Recipient age younger than 30 years and previous xenograft valve were risk factors for late degeneration. We conclude that homovital valves demonstrate good durability, particularly in patients older than 30 years, who had a 10-year freedom from degeneration rate of 97%.

Adolescent↗
PubMed1995

Insulin-like growth factor I is a major fibroblast mitogen produced by primary cultures of human airway epithelial cells.

1. The ability of airway epithelial cells to produce insulin-like growth factor I may be important in the pathogenesis of subepithelial fibrosis observed in the airways of patients with asthma. We determined whether human airway epithelial cells are capable of producing polypeptide mediators that could induce fibroblast proliferative activity, in particular insulin-like growth factor I. 2. We examined 12 primary cultures of human airway epithelial cells grown to confluence on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and subsequent release of Methylene Blue, increased proliferation of human fetal lung fibroblasts was detected in conditioned media from airway epithelial cells. The median stimulation of fibroblast proliferation was 49.9% (range 25.6-113.3%) above control values (observed at 1:2 dilution of media). 3. A neutralizing antiserum to insulin-like growth factor I partly inhibited fibroblast proliferation induced by epithelial cell conditioned media by 52.2% (49.9-109%; n = 5). 4. Radioimmunoassay for insulin-like growth factor I in conditioned media demonstrated a median concentration of 54.1 ng/ml (32.4-96.8 ng/ml). 5. Insulin-like growth factor I mRNA was detected in epithelial cell monolayers by Northern blot analysis using an insulin-like growth factor I cDNA probe. 6. The insulin-like growth factor I gene is expressed in cultured human airway epithelial cells, which also secrete insulin-like growth factor I protein. Insulin-like growth factor I also accounts for the major mitogenic activity for fibroblasts of cultured human epithelial cell conditioned media. Insulin-like growth factor I may function in a paracrine manner to modulate fibroblast behaviour and may be involved in airway processes, such as those occurring in asthma.

Bronchi↗
PubMed1995

Heart transplantation.

Increased experience and knowledge in the field of heart transplantation has resulted in continued expansion of this clinical activity. The same experience has served to identify many problems and provided some answers which are in many instances incomplete. The outstanding problems in heart transplantation are firstly the availability of donor organs, secondly, the limited storage of excised donor hearts and thirdly the conundrum of transplant vascular disease as it is manifested in the coronary arteries of the donor heart. Despite these problems, heart transplantation remains a very effective form of treatment particularly for young, well-motivated patients in end-stage heart failure. Although there is considerable agreement on many of the issues relating to heart transplantation, there are several areas of controversy. Neonatal heart transplantation is one example, though with accumulated experience, acceptance of the procedure has grown. The purpose of this article is to provide an overview of the present situation and to highlight areas of controversy and ignorance which require investigation.

Adult↗
PubMed1995

Cell geometry and contractile abnormalities of myocytes from failing human left ventricle.

OBJECTIVES: Systolic and diastolic dysfunction of the failing human heart may be due to changes in myocyte function, or to extracellular influences such as necrosis, fibrosis or repositioning of viable cells. In order to determine the contribution of cellular factors we have characterised the contraction amplitudes, and contraction and relaxation velocities of single myocytes isolated from failing human left ventricle. METHODS: Myocytes were enzymatically isolated from the left ventricles of 42 subjects, superfused at 32 degrees C and paced at 0.2 Hz. Using a video/edge tracking system we obtained contraction amplitude and contraction and relaxation velocities as well as times to peak contraction (TTP) and to 50% and 90% relaxation (R50 and R90). Concentration-response curves to Ca2+ were constructed for each cell. RESULTS: There was little difference in contraction amplitude at any Ca2+ concentration between cells from failing and non-failing hearts at this low frequency. At maximally activating Ca2+ concentrations (6-20 mM) there was a 30% slowing of relaxation velocity in myocytes from patients with both mild-moderate (P < 0.001) and severe (P < 0.001) congestive heart failure. Contraction and relaxation times were increased in myocytes from failing hearts [TTP: 0.46 +/- 0.02 s (n = 34 patients) vs. 0.35 +/- 0.02 s (n = 6), P < 0.01 and R50: 0.25 +/- 0.02 s (n = 34) vs. 0.16 +/- 0.02 s (n = 6), P < 0.001]. Impaired relaxation was seen with most etiologies, including ischemic and dilated cardiomyopathies and mitral valve disease. Myocytes from failing hypertrophied ventricles were more severely affected than those from failing non-hypertrophied hearts for both contraction and relaxation velocities. Cells from failing hypertrophied ventricles had a significantly larger area than from non-failing or failing non-hypertrophied ventricles, although cell length and sarcomere length were similar between groups. Larger myocytes did not show a more pronounced change in relaxation velocity than normally sized cells from the same hypertrophied ventricle. CONCLUSIONS: Significant impairment of relaxation can be observed in ventricular myocytes from failing human heart under conditions where contraction amplitude appears normal. The defect is not confined to one etiology of disease, but is exacerbated during hypertrophy. An increase in cell size, although observed in myocytes from hypertrophied ventricle, does not itself account for changes in relaxation. Cellular changes contribute to diastolic dysfunction in the failing human heart.

Adolescent↗
PubMed1995

Ondansetron in chemotherapy-induced emesis. Our experience.

UNLABELLED: Chemotherapy-induced nausea and vomiting is one of the major side effects of antiblastic treatment in cancer patients, seriously affecting both the compliance of the patient to therapy and his or her quality of life. OBJECTIVE: The Authors present their experience in the use of ondansetron in 47 patients receiving 186 cycles of chemotherapy for breast or genital neoplasms. RESULTS: Successful control of vomiting was achieved in the first 24 hours, in 74% of the cycles containing cisplatin and 82% of the cycles without cisplatin, if ondansetron was used. On delayed vomiting the difference in results was not as striking as on acute emesis. CONCLUSIONS: The major side effects with ondansetron were headaches (42.4%) and constipation (48.9%). As expected, no extra-pyramidal symptoms were observed in this group, versus 13.3% of the patients treated with metoclopramide.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Cognitive function and behavioural status in paediatric heart and heart-lung transplant recipients: the Harefield experience.

OBJECTIVE: To assess the psychological impact of cardiac and cardiopulmonary transplantation on children. DESIGN: Retrospective cross sectional study. SETTING: One British centre performing paediatric heart and heart-lung transplant operations, four cardiac units in London, three London schools, two London health centres, and the dental department of a London children's hospital. SUBJECTS: 65 children who had been given heart or heart-lung transplants and two reference groups of 52 children who had had other types of cardiac surgery and 45 healthy children. MAIN OUTCOME MEASURES: Development, cognition, and behaviour at home and at school as assessed by measures with proved validity and reliability. RESULTS: Developmental and cognitive measures indicated that children given transplants had significantly lower scores on several parameters, particularly in terms of development in children under 4 1/2 years of age. Performance on all tests, however, was within the normal range. There were no significant differences in behavioural ratings between the transplant and reference groups, though problem behaviour at home was more prevalent in the transplant group. CONCLUSIONS: Though cognitive development may be within the normal range, there are adverse psychological effects associated with cardiac and cardiopulmonary transplantation. These data indicate the need for a controlled prospective study in which children and their families are seen before and at regular intervals after transplantation. Interventions should be developed that are tailored to the particular needs of this very specialised group of paediatric patients and their families.

Achievement↗
PubMed1994

Alloproliferative responses of purified CD4+ and CD8+ T cells to endothelial cells in the absence of contaminating accessory cells.

Human capillary endothelial cells (EC), unlike rodent, constitutively express MHC class II antigens, raising the question of whether they can cause direct stimulation of resting T cells. Although previous reports have demonstrated an alloproliferative response between cultured human EC and resting T lymphocytes, they have not stringently proven the absence of contaminating leukocytes in both stimulator and responder populations. Here, we have quantitated the number of contaminating leukocytes in serially passaged human umbilical vein endothelial cells (HUVEC) and have examined the ability of HUVEC and an EC line (EAhy.926) to cause allostimulation of positively selected CD4+ and CD8+ T cells. Contaminating CD45+ leukocytes were found in primary cultures at a mean level of 0.43 +/- 0.49%; by passages 3 and 4 there were less than 1/10,000 cells. CD4+ and CD8+ T cells were purified by positive selection on antibody-coated Dynabeads and residual DR+ cells were removed by complement-dependent lysis. They were shown to be depleted of monocytes by their failure to proliferate in response to OKT3 and PHA. Nevertheless, the same cells gave an unequivocal response to cytokine-treated, serially passaged HUVEC or EAhy.926 cells. The response of CD4+ but not CD8+ T cells was dependent upon pretreatment of HUVEC or EAhy.926 with human rIFN-gamma. Neither CD4+ nor CD8+ T cells responded to MHC class II-bearing fibroblasts or epithelial cells. The CD8+ T cells that recognized EC did not respond to spleen cells in an MLR. The results confirm that EC, unlike other non-bone-marrow-derived cells, have the ability to provide all the signals necessary for direct stimulation of resting allogeneic T cells.

Antigen-Presenting Cells↗
PubMed1994

A randomized pilot trial of low-dose combination lipid-lowering therapy following coronary artery bypass grafting.

Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting (CABG). There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease. The potential benefit of low-dose lipid lowering combination therapy in these patients has not been investigated. In a randomized, double-blind, placebo-controlled study, we compared the efficacy and safety of a low-dose combination of colestipol 10 g and simvastatin 10 mg/day (CS) to colestipol 10 mg and bezafibrate 400 mg/day (CB) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride < 4.5 mmol/l who had undergone CABG for severe coronary artery disease. In the CS group, total cholesterol decreased by 29% and low-density lipoprotein (LDL) cholesterol by 42%; similarly, CB reduced total cholesterol by 17%, LDL cholesterol by 23%, triglyceride by 19%, and increased high-density lipoprotein (HDL) cholesterol by 14%. Lipoprotein (a) and hemostatic factors were unaffected by either therapy in this study. Both combination therapies were well tolerated with no significant clinical or biochemical side effects. We conclude that low-dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG.

Analysis of Variance↗
PubMed1994

Postoperative hemodynamic improvement with paced linkage of the donor and recipient hearts following heterotopic cardiac transplantation.

It has been shown that following heterotopic heart transplantation the recipient left ventricle ejects more effectively when it contracts out of phase with the donor left ventricle. However, this is rarely the situation, as the two hearts beat independently of one another and the denervated donor heart tends to beat faster than the recipient. In this study the hemodynamic effects of connecting the two hearts by an external temporary dual-chamber pacemaker were evaluated. The donor right ventricle was sensed and the recipient right atrium paced after a timed delay. The delay was adjusted so that recipient systole coincided with donor diastole. Eleven patients were studied in the first postoperative day. Pacing resulted in an improvement in cardiac output from 5.0 to 5.6 l/min (p = 0.003) and a reduction in pulmonary capillary wedge pressure from 16 to 12 mmHg (p = 0.0035). This was associated with a 35% reduction in inotrope requirements. It is concluded that sequential pacing of the two hearts is a useful adjunct to inotropic support in the postoperative period.

Cardiac Output↗
PubMed1994

Cyclosporin pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Effects of pancreatic enzymes and ranitidine.

Cyclosporin (CsA) is currently the main immunosuppressive agent used in organ transplantation with considerable improvement in graft survival. Oral CsA solution is highly lipophilic, and its bioavailability may be reduced in cystic fibrosis (CF) heart-lung transplant recipients with pancreatic, gastrointestinal, and hepatic insufficiency. The bioavailability of oral CsA solution in 7 CF transplant recipients (5 male and 2 female with a mean age of 27 years and a mean weight of 49 kg) and 3 non-CF heart-lung recipients (1 male and 2 female with a mean age of 41 years and a mean weight of 60 kg) was studied. Following intravenous CsA administration, the kinetic curves were similar with no significant difference in the volume of distribution and clearance of CsA demonstrated between the CF and non-CF groups. The mean daily dose of oral CsA in 7 CF subjects (23.3 mg.kg-1) was significantly higher than the 3 non-CF heart-lung recipients (4.8 mg.kg-1). The mean maximum blood concentration of CsA for the oral dose was 776 ng.ml-1 for the 7 CF subjects, which was comparable with the mean peak values of 789 ng.ml-1 for the 3 non-CF control subjects. Poor enteral absorption of CsA probably accounts for the significantly lower mean bioavailability in the 7 CF subjects (14.9%) compared with the 3 non-CF control subjects (39.4%). The effects on the bioavailability of oral CsA solution by pancreatic enzymes (Creon) and histamine-2 antagonist (ranitidine) were also evaluated in the 7 CF subjects. No significant difference was demonstrated.

Administration, Oral↗