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Biomedical subjects

A Gamba

Publications and source records attributed to A Gamba.

At least 19 recordsLinked to original sources

Percolation, morphogenesis, and burgers dynamics in blood vessels formation.

Experiments of in vitro formation of blood vessels show that cells randomly spread on a gel matrix autonomously organize to form a connected vascular network. We propose a simple model which reproduces many features of the biological system. We show that both the model and the real system exhibit a fractal behavior at small scales, due to the process of migration and dynamical aggregation, followed at large scale by a random percolation behavior due to the coalescence of aggregates. The results are in good agreement with the analysis performed on the experimental data.

Computer Simulation↗

Mitral valve repair and transesophageal echocardiographic findings in a high-risk subgroup of patients with active, acute infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Limited data are available regarding the efficacy of mitral valve repair in patients affected by active, acute infective endocarditis. In addition, the predictivity of transesophageal echocardiography (TEE) for guiding the surgical decision-making process in these patients has not yet been reported. The study aim was to evaluate the long-term results of mitral valve repair and role of TEE in active, acute infective endocarditis. METHODS: The study population consisted of patients affected by infective endocarditis of the mitral valve who underwent surgery. TEE was performed intraoperatively to guide the best surgical approach. All patients were followed up (mean 73+/-8 months) after surgery. RESULTS: Twenty-eight patients underwent surgery for infective endocarditis; of these, 13 had mitral valve repair for active, acute infective endocarditis and formed the basis of the study. Sensitivity, specificity, positive predictive value, negative predictive value of TEE in detecting the mechanism of mitral regurgitation were 87%, 100%, 100% and 92%, respectively. The predictivity test of TEE in guiding surgical strategy was 94%. All patients were alive at the time of follow up; 10 (77%) were in NYHA class I and three in class II (23%). Mitral regurgitation was severe in one patient (8%), moderate in three (23%), mild in four (31%), and absent in five (38%). No relapses of active infective endocarditis were observed during the follow up period. CONCLUSION: Mitral valve repair appears to be an effective treatment for active, acute infective endocarditis with mitral regurgitation and should be considered as a therapeutic strategy when surgery is contemplated. TEE has a fundamental role in the surgical decision-making process in these patients.

Acute Disease↗

Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.

BACKGROUND: Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. METHODS: We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. RESULTS: All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. CONCLUSIONS: Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

Adolescent↗

Continuous retrograde warm blood reperfusion reduces cardiac troponin I release after heart transplantation: a prospective randomized study.

During heart surgery, cardiac troponin I (cTn-I) measurement provides a tool to evaluate different cardioprotective techniques. To investigate myocardial protection during heart transplantation (HTx), cTn-I and creatine kinase (CK)-MB release was measured in 42 patients randomized to receving either continuous retrograde warm blood reperfusion or no reperfusion after cold cardioplegia. A significant linear correlation was found between donor heart ischemic time and peaks and the area under the curve of cTn-I and CK-MB release. In patients with an ischemic time longer than 90 min, cTn-I release was significantly lower in those receiving continuous retrograde warm cardioplegia than in controls. No significant difference was observed for CK-MB, tCK, and myoglobin. Our data suggest that the measurement of postoperative cTn-I release may provide a method to evaluate ischemic cardiac damage after HTx. When the ischemic time is longer than 90 min, warm retrograde blood cardioplegia provides better myocardial protection than no reperfusion.

Biomarkers↗

Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Aged↗

[Heterotropic heart transplantation in young patients with elevated pulmonary vascular resistance].

UNLABELLED: Right heart failure due to elevated PVR is one of the major causes of mortality and morbidity after orthotopic heart transplantation. In 5 patients (median age 14 years) with dilated or restrictive cardiomyopathy and important elevation of the PVR, a heterotopic heart transplantation was performed using the technique reported by Yacoub (the donor pulmonary artery was implanted on the recipient right atrium). All the patients presented with at least two of the following parameters: PVR/m2 > 6 U, transpulmonary gradient > 15 mmHg, mean pulmonary pressure > 50 mmHg. One patient with restrictive cardiomyopathy died three months after transplantation of severe failure of the native right ventricle. The other four patients, with a mean follow-up of 29 months, are in good clinical and hemodynamic condition and later post-operative catheterizations showed a progressive reduction of the pulmonary pressure. CONCLUSIONS: Our experience suggests that this type of heterotopic heart transplantation can be performed successfully in patients with secondary pulmonary hypertension. Particular attention should be paid to patients with restrictive cardiomyopathy and important right ventricle dysfunction, in which a complete heterotopic heart transplantation could be a better solution.

Adolescent↗

Optimisation of a stentless valve prosthesis based on an analytic parametric model of the aortic valve.

An analytical mathematical model of a stentless aortic valve has been implemented. The valve is characterised by a trileaflet geometry, cylindrical leaflets; the aortic root is schematised by a conical surface which includes the leaflet attachments. The model is defined through six geometric parameters: the base radius, the valve height, the commissure radius, the leaflet radial, circumferential and attachment line lengths. Five performance indexes have been used to optimise the valve geometry, namely: the systolic area, the leaflet circumferential stress in diastole, the leaflet bending strain in systole and two bending angles related to the rotation of the leaflets from the diastolic to the systolic configuration. The sensitivity analysis is carried out which can identify the influence of each geometric parameter on the performance indexes adopted for the optimum valve design. The analysis of the results provides the geometric configuration which optimises the overall function of the valve throughout the cardiac cycle.

Aortic Valve↗

[Successful medical treatment of Candida tropicalis in prosthetic valve endocarditis].

Medical cure of fungal prosthetic valve endocarditis (PVE) is rarely reported. We describe a patient with C. tropicalis PVE in whom surgery was believed to be contraindicated. A huge tricuspid valvular vegetation was identified by two-dimensional transthoracic echocardiography. After a total of 2 g of amphotericin B, she continued with fluconazole daily with a follow-up of fifteen months. Our patient represents the first case of long term survival of C. tropicalis PVE successfully managed without surgery.

Amphotericin B↗

Fatal aortic Myceliophthora thermophila infection in a patient affected by cystic medial necrosis.

A 22-year-old Italian woman developed fungal aortitis after cardiac surgery for aortic insufficiency. She experienced two episodes of septic embolization and subsequently underwent replacement of the aortic root and initial ascending aorta by a homograft. The lumina of the ascending aorta, aortic arch and the origin of the innominate artery were completely filled with vegetation. From the involved tissue the phaeoid thermophilic hyphomycete Myceliophthora thermophila (Apinis) van Oorschot was isolated in pure culture. This is the second report of isolation of this fungus from humans and the first isolation of a human pathogenic strain of M. thermophila causing fatal vasculitis in a patient affected by cystic medial necrosis. A detailed morphological description of the isolate is also provided.

Adult↗

Synthesis and pharmacological characterization of enantiomerically pure muscarinic agonists: difluoromuscarines.

The four homochiral 4-deoxy-4,4-difluoromuscarine stereoisomers (difluoromuscarines) were prepared in very high enantiomeric excess. A convenient sequence based on the use of natural as well as "unnatural" ethyl lactate allowed the synthesis of target compounds, whose absolute configuration is dictated by that of the starting synthon. Quaternary ammonium salts (+)-5, (-)-5, (-)-6, and (+)-6 were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart) and M3 (ileum and bladder) muscarinic receptor subtypes. The eutomer (+)-5 and distomer (-)-5 were also tested in vivo on pithed rat, and their muscarinic activity at the M1 receptor subtype was compared with those of racemic muscarine [(+/-)-1] and (2S,4R,5S)-4-deoxy-4-fluoromuscarine [(+)-4]. Further pharmacological parameters such as affinity, relative efficacy, and enantioselectivity have been determined for compounds (+)-5 and (-)-5 at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The four homochiral difluoromuscarines behave as muscarinic agonists in all the tests with a potency trend which is different from that previously observed with the 4-deoxy-4-fluoromuscarines and (+/-)-1, thus indicating the intervention of the second fluorine atom on the receptor-ligand interaction. Moreover, the second fluorine atom produces significant differences in the affinity and relative efficacy values of compounds (+)-5 and (-)-5 at M2 and M3 subtypes, which could be attributed to a heterogeneity between the muscarinic receptors mediating heart rate and heart force and those involved in the contraction of ileum and bladder.

Animals↗

The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels.

BACKGROUND: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. HYPOTHESIS: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD. METHODS: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those < 15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mear serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dosew and weighted blood CsA levels (blood CsA levelw). RESULTS: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dosew was the only significant predictor for CAD at multivariate analysis (p < 0.01): there was no correlation with blood CsA levelw. In the patients receiving a CsA dosew > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dosew < 4 mg/kg/day. CONCLUSION: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.

Adolescent↗

Assessment of the influence of the compliant aortic root on aortic valve mechanics by means of a geometrical model.

In recent years several researchers have suggested that the changes in the geometry and angular dimensions of the aortic root which occur during the cardiac cycle are functional to the optimisation of aortic valve function, both in terms of diminishing leaflet stresses and of fluid-dynamic behaviour. The paper presents an analytical parametric model of the aortic valve which includes the aortic root movement. The indexes used to evaluate the valve behaviour are the circumferential membrane stress and the stress at the free edge of the leaflet, the index of bending strain, the bending of the leaflet at the line attachment in the radial and circumferential directions and the shape of the conduit formed by the leaflets during systole. In order to evaluate the role of geometric changes in valve performance, two control cases were considered, with different reference geometric configuration, where the movement of the aortic root was ignored. The results obtained appear consistent with physiological data, especially with regard to the late diastolic phase and the early ejection phase, and put in evidence the role of the aortic root movement in the improvement of valve behaviour.

Aorta↗

Troponin I as a specific marker for heart damage after heart transplantation in a patient with becker type muscular dystrophy.

In a patient with Becker type muscular dystrophy, the development of cardiomyopathy may require heart transplantation, and during both the perioperative period and later it is useful to determine whether myocardial cell damage is occurring; however, the measurement of serum levels of creatine kinase (CK), MB isoenzyme, is not useful because that isoenzyme is released by the dystrophic skeletal muscle, as well as damaged myocardium. Because cardiac troponin I (cTn I) seems to be quite specific for myocardial cells, we reasoned that measurement of serum levels of this protein could distinguish between myocardial damage and skeletal muscle disease in this patient during and after transplantation. During the immediate postoperative period, the time course of the release of total CK (tCK), CK MB mass, myoglobin, and cTn I were different, yielding a peak within 4 hours for CK MB, 24 hours for myoglobin and 36 hours for tCK and cTn I. During the first postoperative year, the patient displayed a release of tCK, CK MB, and myoglobin; cTn I was constantly lower than the reference value for cardiac myocyte necrosis, suggesting the presence of a continuous muscular damage without any myocardial involvement and an accurate specificity of cTn I to differentiate between myocardial and muscular cell damage in patients with neuromuscular disorders.

Adolescent↗

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Adrenergic beta-Antagonists↗

Attitudes toward euthanasia of physician members of the Italian Society for Palliative Care.

BACKGROUND: The problems related to requests for euthanasia by terminal patients; the variations in attitude of palliative care physicians and the possibility that availability of the best palliative care might obviate the problem by eliminating requests for euthanasia, are under discussion. DESIGN: A mailed survey with no possibility of follow-up of all 685 physician members of the Italian Society for Palliative Care (SICP) in 1994. RESULTS: Of the 359 (52.4%) responders, 139 (39%) had received requests for euthanasia; 16 of them (4% of the responders but 11.5% of those who received requests) had complied at least once, while 216 (60%) had not; 125 (35%) thought that euthanasia was 'wrong' under all circumstances; 115 (32%) thought that situations could occur, even in the context of palliative care, in which euthanasia might be ethically 'correct'; 185 (52%) thought that the best palliative care might solve the problem of euthanasia, while 109 (30%) believed otherwise. The variable most strongly associated with a negative attitude toward euthanasia and with the opinion that the best palliative care might be a solution to the problem is religious belief (P < 0.0001). CONCLUSIONS: The attitudes of physicians practising palliative care in Italy are not different from those reported by previous studies which investigated the attitude of other health professionals. There was no agreement about whether the best palliative care might reduce requests for euthanasia by terminal patients.

Adult↗

Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.

Two different anticoagulation protocols were used in 49 consecutive patients mechanically supported either for bridge to transplantation (11) or for recovery of myocardial function after cardiac surgery (35). In 46 patients a Biomedicus centrifugal pump was used and in 3 patients a Pierce-Donachy ventricles. Mechanical support was provided to the left ventricle in 14 patients, to the right ventricle in 6 and to both ventricles in 12 patients; an extra-corporeal membrane oxygenator (ECMO) support was used in 17 patients. Thirty-seven males and 12 females, aged 0.2 to 58 years, were supported for an average time of 6.3 days (range 1-43). Anticoagulation was either based on a continuous infusion of heparin in the first 27 patients (group A) or on a multi-system therapy ("La Pitié" protocol) in the other 22 patients (group B). Overall survival rate was 47%. Patients in group A had a 30% (8/27) survival rate, whereas in group B a 68% (15/22) survival rate was observed (p = 0.006). Transplantation and ventricular assist device (VAD) removal was successfully obtained in 59% (16/27) and 91% (20/22) of patients in group A and group B respectively (p = 0.05). Significant bleeding occurred in 21 patients (81%) in group A and in 2 (9%) of group B (p = 0.001). In these patients bleeding averaged 230 +/- 231 ml/kg in group A versus 55 +/- 18 ml/kg in group B (p = 0.001). Surgical revision was necessary for cardiac tamponade or persistent bleeding in 12 patients of group A (25 procedures: mean 0.9/patient) and in 3 patients of group B (one each patient: mean 0.1/patient) (p = 0.01). Infection, thrombo-embolism and brain hemorrhage were also less frequent in group A than in group B. Our data suggest that the "La Pitié" protocol provides a better control of bleeding than the conventional heparin infusion in patients receiving assist device. this reduction in thrombo-hemorrhagic complications might improve the results of mechanical circulatory support.

Adolescent↗