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Biomedical subjects

M Yacoub

Publications and source records attributed to M Yacoub.

At least 145 records · Page 8Linked to original sources
PubMed1994

Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: radionuclide imaging with technetium-99m 2-methoxy isobutyl isonitrile.

OBJECTIVES: We sought to determine the incidence of late perfusion defects attributable to coronary artery mobilization in patients undergoing anatomic correction for complete transposition of the great arteries. BACKGROUND: Anatomic correction (arterial switch procedure) is currently the surgical treatment of choice for complete transposition. From its conception, there has been concern about the impact on myocardial perfusion of the coronary artery mobilization and reimplantation involved in the correction. Previous studies have demonstrated myocardial perfusion defects in patients after correction, although a causal relation between coronary mobilization, and perfusion abnormality has not been established. METHODS: In a case-comparison study designed to test this hypothesis, 29 children underwent imaging with technetium-99m 2-methoxy isobutyl isonitrile (technetium-99m mibi). Ten had undergone anatomic correction (arterial switch group; interval from operation 6.9 +/- 1.42 years [range 4.9 to 9.1]); 9 had required noncoronary open heart surgery for other cardiac lesions (post-bypass group; interval from operation 5.6 +/- 3.6 years [range 1.0 to 13.25]); and 10 had had no surgical procedure (control group). The latter group comprised children with atrial or ventricular septal defects who required a radionuclide study for shunt calculation. Planar studies were performed in all 29 children, and additional tomographic acquisition was achieved in 25. To assess reversibility of perfusion defects both an exercise and a rest planar study were performed in the arterial switch group. RESULTS: Perfusion abnormalities were observed in seven of the nine children in the postbypass group and in all 10 children in the arterial switch group. The frequency of perfusion defects in these two groups was similar, with at least 25% of the tomographic segments reported being abnormal. The control group had significantly fewer defects than the other two groups (p = 0.02), with only 8% of the tomographic segments judged to be abnormal. In all except one patient in the arterial switch group, the segments reported as abnormal on the planar exercise study were either abnormal or equivocal on the rest study, indicating a fixed abnormality. CONCLUSIONS: Although the precise etiology of these perfusion abnormalities cannot be defined from this study, these data suggest that their origin is related more to the insult of open heart surgery itself than to the coronary manipulation involved in the arterial switch procedure. The functional importance requires further study.

Cardiac Surgical Procedures↗
PubMed1994

Human endothelial stimulation of allogeneic T cells via a CTLA-4 independent pathway.

It is accepted that T cells require at least two signals to undergo proliferation and cytokine release: an antigen dependent signal mediated via the the TCR (T cell receptor) and an antigen independent signal mediated via one or more accessory or adhesion molecules. Interaction between CD28 or CTLA-4 and the B7 co-receptors found on many antigen presenting cells (APC) is known to be essential for antigen specific (including alloantigen) expansion of T cells in vitro and in vivo. CTLA-4-Ig is a fusion protein with very high affinity for B7. It has been used in vivo to block both allograft and xenograft rejection. Most of the work investigating second signal requirement has used 'professional' APC. In view of the observations that class II positive human endothelial cells can cause direct allostimulation of resting CD4+ and CD8+ T cells, we have investigated the requirement of CTLA-4 in this response. The current studies show that the proliferative response of allogeneic CD4+ and CD8+ T cells to interferon-gamma treated HUVEC (human umbilical vein endothelial cells) is inhibited by monoclonal antibodies (mAbs) against MHC class II and class I antigens, respectively, but not by CTLA-4-Ig. In contrast, lymphocytes proliferating in response to allogeneic splenocytes are inhibited by CTLA-4-Ig. Cell surface binding studies using flow cytometry demonstrated failure of endothelial cells to bind either CTLA-4-Ig or mAbs against B7 receptors. In conclusion, different APC use different co-stimulatory signals. The possibility that this leads to different cytokine profiles needs to be investigated to further understand the role of endothelial cells in transplant rejection.

Abatacept↗
PubMed1994

Coronary artery surgery in women compared with men: analysis of coronary risk factors and in-hospital mortality in a single centre.

OBJECTIVE: To determine differences in coronary risk factors between women and men and their relation to in-hospital mortality associated with coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: A regional cardiothoracic centre. PATIENTS: 482 (362 (75%) men and 120 (25%) women) consecutive patients who had primary isolated coronary artery bypass grafting. RESULTS: The women were on average three years older than the men (63 v 60 years, P < 0.001). Women more frequently had hypertension (47% v 33%, P < 0.01), diabetes mellitus (21% v 10%, P < 0.005), hypothyroidism (9% v 2%, P < 0.003), and a family history of premature coronary heart disease (49% v 31%, P < 0.0006). More of the men were cigarette smokers (67% v 45%, P > 0.00001). Many of the women and men had dyslipidaemia. Postmenopausal women had a higher concentration of serum total cholesterol than men of a comparable age, (7.3 mmol/l v 6.5 mmol/l, P = 0.0002). Although arterial grafts were often used in both sexes, they were more often used in men than in women (91% v 78% respectively, P = 0.0003). In-hospital mortality was 2.1% (1.4% in men and 4.2% in women, P = 0.14). The estimated one year probability of survival in men who had survived 30 days was 0.99 with 95% confidence interval 0.98 to approximately 1 while that for women was 0.97 with 95% confidence interval 0.91 to approximately 1. Univariate analysis showed that preoperative history of diabetes mellitus was a predictor of mortality (P = 0.03). CONCLUSION: There were differences in the incidence and type of risk factors in men and women who had coronary artery bypass grafting. Preoperative diabetes mellitus was a predictor of in-hospital mortality.

Age Distribution↗
PubMed1994

Complete atrioventricular septal defect with tetralogy of Fallot: diagnosis and management.

OBJECTIVE: To report recent experience of patients with complete atrioventricular septal defect and tetralogy of Fallot, with emphasis on anatomical features, diagnosis, and management. DESIGN: Case notes were reviewed and patients were assessed at follow up by clinical examination and cross sectional and Doppler echocardiography. SETTING: Tertiary cardiothoracic referral centre. PATIENTS: Between 1987 and 1992 13 patients with atrioventricular septal defect and tetralogy of Fallot (12 with concordant and one with double outlet ventriculoarterial connections) underwent surgery; 10 underwent complete intracardiac repair. 11 patients had Down's syndrome. The complete diagnosis was established preoperatively by cross sectional echocardiography in all but one patient. A tri-leaflet left atrioventricular valve as seen in parasternal short axis views was the diagnostic feature of atrioventricular septal defect, with tetralogy of Fallot diagnosed from the presence of anterocephalad deviation of the outlet septum producing subvalvar pulmonary stenosis as seen in subcostal right anterior oblique views. INTERVENTIONS: Total correction consisted of closure of the atrioventricular septal defect by a combined right atrial and ventricular approach, reconstruction of the atrioventricular valves, and relief of the obstruction within the right ventricular outflow tract. Separate patches were used to close the atrial and ventricular septal defects. Modified Blalock-Taussig shunts were performed in three patients, who await intracardiac repair. Surgical correction was carried out at mean (range) age of 5 (2 to 15) years. MAIN OUTCOME MEASURES: Diagnostic methods, surgical results, and functional state after complete correction. RESULTS: The presence of an atrioventricular septal defect was missed preoperatively in one patient with tetralogy of Fallot. The characteristic goose neck deformity on the left ventriculogram was not present and the tri-leaflet nature of the left atrioventricular valve was not sought on echocardiography. Of the 10 patients who underwent complete repair, nine are alive and one died 34 days after operation with adult respiratory distress syndrome. Examination at necropsy showed an excellent surgical correction. Mean (range) follow up was 23 (8 to 48) months. All nine patients are alive and well (New York Heart Association Class 1). CONCLUSION: Accurate diagnosis and staged management with improved surgical techniques have lowered mortality of this complex combination of cardiac defects. The current policy of this group is to recommend a systemic to pulmonary arterial shunt procedure for symptomatic children younger than 2 years and total correction in older children.

Adolescent↗
PubMed1994

Congenital cutis laxa with a dominant inheritance and early onset emphysema.

Two cases (mother and daughter) are reported of autosomal dominant cutis laxa which are unusual in being associated with early onset emphysema. Both mother and daughter have been smokers and are heterozygotes for the alpha 1 antitrypsin genotype. The combination of cigarette smoking and subnormal alpha 1 antitrypsin levels may explain the pulmonary spread in these two women who have what is usually a benign form of cutis laxa limited to the skin.

Adult↗
PubMed1994

Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure.

BACKGROUND: Patients with advanced heart failure have bioenergetic abnormalities of skeletal muscle metabolism during exercise. Using 31P magnetic resonance spectroscopy, we sought to determine whether skeletal metabolic responses to exercise are normalized by orthotopic cardiac transplantation. METHODS AND RESULTS: Four groups were studied: healthy normal volunteers (n = 9), subjects awaiting heart transplantation (n = 10), subjects < 6 months (mean, 4 months) after transplant (n = 9), and subjects > 6 months (mean, 15 months) after transplant (n = 8). None of the posttransplant patients had biopsy evidence of rejection at the time of study. There were no significant differences in age, preoperative functional class, or symptom duration among the three patient groups. Metabolic responses were monitored in the dominant arm during incremental weight pull exercise and 10 minutes of recovery by 31P magnetic resonance spectroscopy, with measurement of pH and the phosphocreatine (PCr)/(PCr + inorganic phosphate [Pi]) ratio, an index of PCr concentration. In addition, based on recovery data, the rate of PCr resynthesis was calculated as a measure of oxidative metabolism that is independent of work level, recruitment, or muscle mass, and the effective maximal rate of mitochondrial ATP synthesis (Vmax) was determined. Analysis was by ANOVA. There were no differences between groups in pH or PCr/(PCr + Pi) at rest. Compared with the normal control group, the pretransplant group had a decreased exercise duration (11.3 +/- 2.5 versus 15.0 +/- 1.3 minutes, P = .02), a lower submaximal exercise PCr/(PCr + Pi) ratio (0.58 +/- 0.11 versus 0.76 +/- 0.08, P < .05), a reduced PCr resynthesis rate (13 +/- 6 versus 22 +/- 9 mmol/L per minute, P < .05), and a lower calculated Vmax (26 +/- 14 versus 53 +/- 26 mmol/L per minute, P < .05). In the group studied early after transplantation, all the changes noted in the pretransplant group persisted and were if anything somewhat worse. In the group studied late after transplantation, there was a significant improvement in the PCr resynthesis rate compared with the early-posttransplant group (27 +/- 6 late versus 15 +/- 6 mmol/L per minute early, P < .05) and statistically nonsignificant trends toward improvements in submaximal exercise pH (6.86 +/- 0.24 late versus 6.72 +/- 0.24 early) and submaximal PCr/(PCr + Pi) ratio (0.56 +/- 0.14 late versus 0.44 +/- 0.15 early) and Vmax (45 +/- 21 late versus 33 +/- 15 mmol/L per minute early). However, compared with normal subjects, exercise duration and submaximal PCr/(PCr + Pi) were still reduced in the late-posttransplant group. CONCLUSIONS: Despite successful heart transplantation, skeletal muscle abnormalities of advanced heart failure persist for indefinite periods, although partial improvement occurred at late times. The persistent abnormalities may contribute to the reduced exercise capacity that is present in most patients after transplantation.

Energy Metabolism↗
PubMed1994

Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation.

BACKGROUND AND PURPOSE: Heterotopic cardiac transplantation is a valuable surgical technique that maximizes the use of donor organs. However, recipient heart function may decline steadily postoperatively with resulting clinical deterioration. Paced linkage has the potential of reducing afterload and enhancing coronary flow of both hearts, thereby improving recipient- and donor-heart function. This may have long-term as well as short-term benefits. METHODS AND RESULTS: The study was performed on 11 heterotopic transplant recipients. The two hearts were linked with a pacemaker (paced linkage) to produce recipient heart systole during different periods of donor-heart diastole. The recipient ventricular contraction was timed to occur during early, mid, and late diastole of the donor heart. Hemodynamic baseline measurements were compared with the optimal counterpulsated data. Paced linkage produced significant improvements in total cardiac output, 5.0 +/- 0.9 compared with baseline 4.5 +/- 0.8 L/min (P = .021); recipient coronary sinus flow, 278 +/- 145 versus 186 +/- 108 mL/min (P = .022); and aortic systolic pressure, 135 +/- 27 versus 123 +/- 27 mm Hg (P = .005). There was an overall improvement in systolic ventricular performance in the recipient heart when pace linked, as evidenced by a significant increase in left ventricular systolic pressure of 118 +/- 36 compared with the baseline value of 108 +/- 33 mm Hg (P = .016), an increase in ejection period from 174 +/- 30 versus 203 +/- 48 (P = .046), and a decrease in the pre-ejection period of 147 +/- 37 when paced versus 181 +/- 39 milliseconds (P = .013). The metabolic studies showed a significant decrease in hypoxanthine release from a baseline level of 0.4 mumol/L to a paced value of -0.06 mumol/L (P = .002); these very low values would suggest that there is no evidence of ischemia. Hemodynamic changes in the donor heart included a significant reduction in the left ventricular end-diastolic pressure from 6.8 +/- 4.4 versus baseline of 10.5 +/- 5.8 mm Hg (P = .029) and in maximum -dP/dT from 3.2 +/- 1.7 versus baseline of 2.1 +/- 1.1. CONCLUSIONS: Paced linkage after heterotopic cardiac transplant produces significant functional improvements in both hearts. Permanent pacemaker implantation may sustain these acute benefits and prevent the premature deterioration of the recipient heart.

Adult↗
PubMed1994

Pretransplant clinicopathological correlation in end-stage primary pulmonary hypertension.

The aim of the study was to see if there was any correlation between the histopathology, ultrastructure, pulmonary endocrinology and clinical manifestations of end-stage primary pulmonary hypertension. Twenty patients undergoing heart-lung transplantation for the disease were studied. The nature and duration of symptoms and signs, results of haematological, electrocardiographic, radiographic, echocardiographic and haemodynamic studies, and the response of patients to vasodilators were compared with data from histopathological and ultrastructural study of lungs removed at transplantation. Length of clinical history and clinical evidence of severe disease were not necessarily associated with advanced histopathology, nor did the presence of small, contracted muscular pulmonary arteries imply responsiveness to vasodilators. Numbers of gastrin-releasing peptide-containing pulmonary endocrine cells were greater in lungs in which there was activity of myofibroblasts in pulmonary arterial vessels, and correlated negatively with mean pulmonary artery pressure and pulmonary artery systolic pressure. Whereas the prognosis of primary pulmonary hypertension cannot as yet be defined by other than its clinical manifestations, intimal proliferation as well as vasoconstriction may be important in its pathogenesis. The release of gastrin-releasing peptide from pulmonary endocrine cells may possibly be involved in this process.

Adolescent↗
PubMed1994

[Distant heart procurement in the Czech and Slovak Republics].

Heart transplantation (HTx) became an established treatment of the end stage heart failure. The limiting factor of transplantation activity is the availability of donors which could be expanded by multiorgan harvesting and distant heart procurement (DHP). In spite of the fact that only 4-5 hours of could ischaemia (CI) is favourable it is still acceptable to organize the DHP within the radius over 1000 km from a recipient hospital. Good co-ordination, he best communication and transportation technology are absolutely necessary. Only in the case when there is no local recipient on the waiting list fr the HTx we offer an organ abroad. Paediatric Transplant Center Motol has been offered such 19 heart donors since 1992. 7 of them were accepted and in 4 (donor age 10-40 y.) successful DHP was performed, the organs were transported (900-1100 km) and HTx were performed at Harefield Hospital, UK. CI was 4:20-5:05 hours (mean 4:36). Two organs were used for orthotopic HTx (OHTx), two for heterotopic HTx (HHTx). Two failed due to the acute rejection. One was successfully retransplanted, went into chronic renal failure and is maintained on dialysis. Another recipient died 1 w. after HHTx due to the failure of his own heart. One recipient has been living already 1 y. since his OHTx. This experience demonstrates the ability and competence to organize and perform the DHP by a local team even in our conditions. We consider it suitable and necessary prerequisite to be able to start our own paediatric HTx programme.

Adolescent↗
PubMed1994

[Idiopathic pulmonary hemosiderosis, celiac disease and cardiomyopathy].

UNLABELLED: BACKGROUND--Idiopathic pulmonary hemosiderosis (IPH), a rare and possibly immune disease, is sometimes associated with coeliac disease and myocardiopathy. CASE REPORTS: CASE NO 1--A 2 year-old boy with IPH was investigated because he suffered from frequent, soft stools. Small bowel biopsy showed partial villous atrophy. Circulating gliadin antibodies were present. The patient was placed on a gluten-free diet. CASE NO 2--An 8 year-old girl was admitted because she suffered from severe anemia (Hb: 4 g/100 ml). She was found to have IPH and myocardiopathy. She had no manifestation, but a systematic search for coeliac disease was positive (total villous atrophy; presence of circulating gliadin and alveolar basement membrane antibodies). The patient was placed on a gluten-free diet, prednisone and diuretics, but she died during a relapse 2 months later. CONCLUSION--It is worthwhile checking for coeliac disease in all patients with IPH. The presence of myocardiopathy is a negative prognosis.

Cardiomyopathies↗
PubMed1994

Orthotopic cardiac transplantation for dilated cardiomyopathy after allogeneic bone marrow transplantation.

We report the case of a 26-year-old man with acute myeloid leukemia (AML) who underwent bone marrow transplantation (BMT) from an HLA-identical sibling-donor when in first complete remission. He developed a dilated cardiomyopathy 9 months post-BMT and subsequently underwent orthotopic heart transplantation. He remains in complete hematological remission more than 12 months after surgery with normal cardiac function and an excellent performance status. Although cardiac transplantation has been carried out for chemotherapy-induced cardiomyopathy in cancer patients, to our knowledge cardiac transplantation following BMT has not been reported previously.

Acute Disease↗
PubMed1994

The use of unstented homograft valves for aortic valve reoperations. Review of a twenty-three-year experience.

Unstented homograft valves offer several theoretical advantages when used for patients who have had previous operations on the aortic valve. Between January 1970 and February 1993, 177 patients received unstented homograft valves after previous aortic valve operations. One hundred thirty-four patients had previous aortic valve replacement in the form of homografts (101 patients), mechanical prostheses (24 patients), and bioprostheses (9 patients), and 43 had previous valve repair. The indication for reoperation was deterioration of a noninfected valve (124 patients), infective endocarditis (40 patients), and failure of a noninfected mechanical valve (12 patients). Fresh homograft valves were implanted in 60 patients, homografts preserved in antibiotics were used in 111 patients, and 6 patients received cryopreserved valves. Aortic valve and root replacement was performed in 60 patients, and in 117 the homograft was inserted freehand in the subcoronary position. The early mortality was 5.1%. The actuarial survival at 10 years was 71%. Multivariate analysis demonstrated that patients with previous homograft replacement have a better long-term survival than patients who had previous mechanical valves (p = 0.017). The freedom from valve-related death and reoperation was 70% at 10 years. Fresh homografts faired better than antibiotic-sterilized homografts (p = 0.007). None of the patients had recurrence of endocarditis at 6 months, although 1 patient died of uncontrolled infection despite valve replacement. The freedom from recurrent endocarditis was 88% at 10 years. We conclude that unstented aortic homografts provide good early and long-term results for aortic valve reoperations, particularly in patients with previous homograft replacement. Recurrent endocarditis is uncommon even in patients operated on for prosthetic valve infections.

Adolescent↗
PubMed1993

Long term follow up of severely ill patients who underwent urgent cardiac transplantation.

OBJECTIVE: To assess long term survival (> 5 years) and quality of life in severely ill patients referred for urgent cardiac transplantation. SETTING: Tertiary referral centres: before transplantation at the National Heart Hospital (late 1984 to end 1986); after transplantation at Harefield Hospital. SUBJECTS: Eighteen patients (15 men; three women) who had required intensive support in hospital before cardiac transplantation and were alive at short term follow up. INTERVENTIONS: Intravenous infusions of cardiac drugs (mean 2.2 infusions), intravenous diuretics (17 patients), and many other drugs before transplantation. Intra-aortic balloon counterpulsation (four patients), temporary pacing (two), and resuscitation from cardiac arrest (three). Patients had specialised nursing care on a medical intensive care unit in almost every case. MAIN OUTCOME MEASURES: Long term survival in patients after urgent cardiac transplantation and perceived quality of life. RESULTS: Of 18 patients who were alive at short term follow up (mean (range) 19.4 (10-33) months), 14 were still alive in 1992 (69 (61-83) months). Ten still worked full time, and 11 reported no restrictions in their daily activities. Three of four patients who died in the intervening period survived > 5 years after transplantation. Overall, 17 of 18 patients survived at least 5 years. CONCLUSIONS: In severely ill patients who undergo urgent cardiac transplantation and survive in the short term, long term (5-7 year) survival and quality of life seem good.

Cardiomyopathy, Dilated↗
PubMed1993

Long-term growth following neonatal anatomic repair of transposition of the great arteries.

Despite generally normal prenatal growth, surviving infants with transposition of the great arteries (TGA) frequently develop severe and progressive growth impairment which is not always fully reversed by elective atrial repair within the first year of life. This study was undertaken to determine the effect of neonatal anatomic repair of TGA on long-term growth. Twenty-three children with uncomplicated TGA were followed for a mean of 60 (12-90) months after anatomic repair at a mean age of 11 (1-40) days. Standardized measurements of weight, height, and head circumference for both patients and normal siblings were expressed as percentiles as well as in Z scores (in standard deviations from the mean for age and sex) based on internationally recognized standards. At latest follow-up, 22 (96%) of the patients were above the 3rd percentile for weight and 21 (91%) for both height and head circumference, with 13 (57%), 11 (48%), and 13 (57%) above the 50th percentile for each respective parameter. The mean Z scores (+/- SD) for weight, height, and head circumference for the patient group were -0.1 +/- 1.2, -0.2 +/- 1.3, and -0.1 +/- 1.1, respectively, and did not differ significantly from those of the reference population (p > 0.05 for each comparison). Paired comparisons of mean Z scores for each growth parameter with those of 35 normal siblings demonstrated no significant difference for weight or height and a small but significant difference for head circumference. Age at surgical repair (within the first 6 weeks of life), duration of follow-up and the development of moderate supravalvar pulmonary stenosis were not statistically related to long-term growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗