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Biomedical subjects

M Di Donato

Publications and source records attributed to M Di Donato.

At least 19 recordsLinked to original sources
PubMed2005

Expression of single-chain antibodies in transgenic plants.

There is an ever-growing interest in plant molecular farming as a system for producing valuable recombinant pharmaceutical molecules, such as single-chain variable fragments, on an industrial/agricultural scale and it appears that it is going to become a reality. Human epidermal growth factor receptor-2 (HER2) is an oncogene involved in abnormal cell growth in breast cancer and is considered for the development of new cancer therapies. We describe here the cloning and expression of a scFv-alpha HER2 that has been produced in Escherichia coli and in plants using both stable and transient systems in tobacco and Nicotiana benthamiana. Single-chain antibodies (ScFvs) extracted and purified from E. coli and plant tissues were tested for functionality and specificity by flow cytometry analysis on several cell lines and showed positive results when used on breast cancer slides coming from human frozen tissues. As a result, scFv-alpha HER2 represents a good opportunity for application and use in diagnosis and therapy.

Animals↗
PubMed2003

Surgical treatment of ventricular septal defect complicating acute myocardial infarction. Experience of a north Italian referral hospital.

The purpose of our study was to evaluate the clinical outcome of postinfarction ventricular septal defect (VSD) of patients referred to our institution for surgical treatment, by assessing the role of several operative, pre- and post-operative variables on mortality. The medical records of 58 consecutive patients (mean age 73+/-7 years), operated on after 14+/-12 days from the acute myocardial infarction were retrospectively reviewed and the data were analyzed. Associated procedures were left ventricular reconstruction in 13 patients and aortocoronary bypass grafting in 47 (81%). The overall operative, in-hospital mortality rate was 52% (75% in patients operated on within the first week and 16% if time from infarct to surgery was >3 weeks). Time from AMI to surgery and time from hospital admission to operation were significantly shorter in non-survivors (p=0.003 and 0.012, respectively). Other pre-operative variables significantly associated with mortality were: cardiogenic shock, pulmonary pressure, VSD diameter. In conclusion, time from AMI to operation appears to be a very important prognostic factor. However, size of VSD and hemodynamic conditions significantly influence the mortality. Moreover, concomitant procedures of revascularization can be safely performed, when required, as actually occurs in most cases.

Aged↗
PubMed2002

Ischemic mitral regurgitation: intraventricular papillary muscle imbrication without mitral ring during left ventricular restoration.

OBJECTIVES: Functional mitral regurgitation in ischemic cardiomyopathy carries a poor prognosis, and its surgical management remains problematic and controversial. The aim of this study was to report the results of our surgical approach to patients who have had myocardial infarctions and have ventricular dilatation, mitral regurgitation, reduced pump function, pulmonary hypertension and coronary artery disease. This surgical approach consists of endoventricular mitral repair without prosthetic ring, ventricular reconstruction with or without patch, and coronary artery bypass grafting. PATIENTS: Forty-six patients (aged 64 +/- 10 years) with previous anterior transmural myocardial infarction and mitral regurgitation comprised the study group. Indication for surgery was heart failure in 93% of cases; 25 patients were in New York Heart Association functional class IV and 17 were in class III. Mitral regurgitation was moderate to severe in 32 cases (69%). RESULTS: All patients underwent coronary artery bypass grafting, with a mean of 3.2 +/- 1.3 grafts. Associated aortic valve replacement was performed in 4 cases. Global operative mortality rate was 15.2%. End-diastolic and end-systolic volumes significantly decreased after surgery (from 140 +/- 40 to 98 +/- 36 mL/m(2) and from 98 +/- 32 to 63 +/- 22 mL/m(2), respectively, P =.001). Systolic pulmonary pressure decreased significantly (from 55 +/- 13 to 43 +/- 16 mm Hg, P =.001). Ejection fraction did not change significantly. Postoperative mitral regurgitation was absent or minimal in 84% of cases; 1 patient had severe mitral regurgitation necessitating valve replacement. New York Heart Association functional class significantly improved. The mean preoperative functional class was 3.4 +/- 0.6 (median 3, range 2-4); after the operation, this decreased to 1.9 +/- 0.7 (median 2, range 1-3, P <.001). Cumulative survival at a 30-month follow-up was 63%. CONCLUSIONS: Our aggressive, combined surgical approach is aimed at correcting the three components of ischemic cardiomyopathy: relieving ischemia, reducing left ventricular wall tension by decreasing left ventricular volumes, and reducing volume overload and pulmonary hypertension by repairing the mitral valve. Despite a relatively high perioperative mortality rate, surviving patients benefitted from the operation, with improved clinical functional class and thus quality of life.

Adult↗
PubMed2001

Left ventricular reconstruction by endoventricular circular patch plasty repair: a 17-year experience.

The first experience with endoventricular circular patch plasty (EVCPP) was reported in 1984 as a surgical method to rebuild left ventricular (LV) geometry made more spheric after myocardial infarction. The consequence is dilated ischemic cardiomyopathy. In anterior infarction, the free LV wall and septum are scarred and become dyskinetic or akinetic. The fundamental approach excludes the noncontractile (asynergy) and nonresectable regions to restore more normal size and shape. The current experience of our group in 2001, includes 1,011 patients, and confirmation of our results by others, including an international team. The basic components are LV reconstruction, revascularization, and mitral repair (when needed), which form an integrated method of surgical management. Endocardiectomy and cryoablation are used with spontaneous and inducible ventricular arrhythmias. This article reviews these results and summarizes 10 important points concerning the surgical treatment of ischemic dilated cardiomyopathy that may provide guidelines for the future. These data indicate EVCPP, and its variations, form the central theme in surgical treatment of congestive heart failure.

Arteries↗
PubMed2001

Intermediate survival and predictors of death after surgical ventricular restoration.

This study examined the effects of Dor procedure on long-term survival in patients with previous transmural anterior myocardial infarction who were referred to a single experienced center for left ventricular reconstruction by endoventricular patch-plasty repair. Our aim was to evaluate the impact of this procedure on long-term survival and to assess the ability of preoperative, perioperative, and postoperative variables to predict late survival. Major indications for surgery were left ventricular dysfunction, angina, ventricular arrhythmias, or a combination of the three; 20 patients underwent urgent cardiac surgery. The total group was 245 patients, with 8.1% hospital mortality, and 19 patients lost to follow-up [corrected]. The study group comprised 207 patients. Many pre- and postoperative clinical, hemodynamic, and functional variables, as well as operative parameters, were studied by univariate analysis. During a mean follow-up period of 39+/-19 months, 30 end points were observed, including 27 deaths and 3 heart transplants. Event-free survival was 98%+/-1% at 1 year, 95.8%+/-1.4% at 2 years, and 82.1%+/-3.3% at 5 years. Cox regression analysis showed preoperative New York Heart Association functional class, ejection fraction, end systolic volume index, and remote asynergy as independent predictors of mortality. The procedure has a favorable impact on 5-year survival. Independent predictors of late survival are the preoperative functional status and the left ventricular systolic function.

Cardiovascular Surgical Procedures↗
PubMed2001

Inferior wall restoration: anatomic and surgical considerations.

Congestive heart failure that results from inferior infarction is caused by a triangular change in ventricular geometry, which involves the septum, lateral wall, and base supplied by the right coronary artery. The extent of damage is determined by the anatomic distribution of coronary blood flow. Mitral insufficiency is accentuated from damage to the basal region, especially when the occluded right coronary vessel has multiple inferior branches and wraps around the apex. Three methods of repair are described, and include direct restoration without a patch, patch repair of the triangular scar, or use of a retriangulation suture in ventricles with trabecular scar to imbricate the noncontractile region to restrict patch size. This triangular reduction in size mirrors the design concept for suture described by Fontan in anterior infarction, which produces an oval apex. Early results in relation to left ventricular end systolic volume index and ejection fraction are defined.

Cardiovascular Surgical Procedures↗
PubMed2001

Surgical ventricular reconstruction and mitral regurgitation: what have we learned from 10 years of experience?

Ischemic mitral regurgitation is functional, and caused predominantly by ventricular dilatation, with secondary functional changes related to annular dilatation, tethering of leaflets from distension, and intraventricular widening between papillary muscles, in the absence of chordal rupture. The treatment includes dealing with the mitral-ventricular interaction by combining surgical ventricular restoration and coronary bypass grafts (CABGs) to alter fiber orientation and muscle nourishment, with annuloplasty, decreasing left ventricle (LV) cavitary volume to reduce abnormal lengthening for tethering, and narrowing the distance between papillary muscles to restore a more normal transverse diameter. These interventions are performed during surgical ventricular restoration (SVR), and the annuloplasty is performed within the ventricle. The cavitary size after SVR must not be restrictive, and methods of patch angulation to restore an elliptic chamber, and interventions to avoid too small a LV cavity are discussed as we summarize 10 years of experience with SVR in 924 patients, and analyze interventions for mitral insufficiency in a recent 3-year subset of 363 patients. The integrated response to the vessel, ventricle, and valve are the central themes of management.

Aged↗
PubMed2001

Surgical ventricular restoration in patients with postinfarction coronary artery disease: effectiveness on spontaneous and inducible ventricular tachycardia.

Surgical ventricular reconstruction (SVR) involves resection of scar, septal exclusion, cavity reduction by endoventricular patch, and complete coronary grafting. At the Cardiothoracic Centre of Monaco, ventricular stimulation (PVS) is performed before SVR, unless contraindicated. In patients with spontaneous and/or inducible ventricular arrhythmias, nonguided endocardiectomy and cryosurgery are added. We report clinical and hemodynamic results after SVR in postinfarction patients, to compare management of patients with spontaneous and/or inducible ventricular tachycardia, with those without arrhythmias. The 3 subsets were: Group A, 87 patients with clinical documented ventricular arrhythmias and inducible or not inducible ventricular tachycardia (Spontaneous); Group B, 105 patients without clinical ventricular arrhythmias but with inducible ventricular tachycardia at PVS (Inducible); and Group C, 190 patients without spontaneous arrhythmias and not inducible ventricular tachycardia at PVS (No arrhythmias). Overall surgical mortality rate was 7.6% (29 of 382). Sudden death mortality was only 18.7% of all deaths. Surgical management caused marked reduction of inducible ventricular tachycardia, from 144 of 352 inducible ventricular tachycardia before surgery (41%), to 26 of 307 (8%) at early study, and 14 of 177 (8%) one year later. Cardiac mortality was low at 5 years, and not different among groups; this indicates that the surgical procedure limits the ventricular arrhythmias that normally impair prognosis in postinfarction dilated cardiomyopathy. We believe the favorable electrical success rate and low mortality are not linked to one aspect of the surgical procedure, but to an integrated approach that relieves ischemia (coronary bypass graft), and reduces left ventricular volumes (SVR) to improve pump function, and nonguided endocardiectomy plus cryoablation, to interrupt functional reentry circuits.

Cardiovascular Surgical Procedures↗
PubMed2001

Surgical anterior ventricular endocardial restoration (SAVER) for dilated ischemic cardiomyopathy.

Anterior infarction changes ventricular shape and volume. Akinesia is most commonly observed after early reperfusion. Dyskinesia develops in the absence of reperfusion. Both produce heart failure by dysfunction of the remote muscle. Traditional surgery deals with dyskinesia. This study evaluates surgical anterior ventricular endocardial restoration (SAVER), an operation that excludes the apical and septal scar in both akinesia and dyskinesia. A new international group of cardiologists and surgeons from 13 centers, the RESTORE Group) investigated SAVER in ischemic cardiomyopathy following anterior infarction. From January 1998 to July 2000, 662 patients underwent surgery. Early and 3-year outcomes were investigated. Concomitant procedures included coronary artery bypass grafting (CABG) in 92%, mitral repair in 22%, and mitral replacement in 3%. Hospital mortality was 7.7%. Mortality among 606 patients with SAVER and CABG alone was 4.9%. It was 8.1% among 147 patients who underwent concomitant mitral valve repair. Few patients required IABPs (8.4%), LVADs (0.4%), or ECMO (0.6%). Postoperatively, ejection fraction increased from 29.7% +/- 11.3% to 40.0% +/- 12.3% and left ventricular end systolic volume decreased from 96 +/- 63 to 62 +/- 39 mL/m(2) (P <. 05). At 3 years, the survival rate was 89.4% +/- 1.3%. Survival was lower among those with preoperative volume >80 mL/m(2) compared with volume < or = 80 mL/m(2) (83.5% +/- 3.3% v 94.5% +/- 2.0%). Freedom from readmission to hospital for heart failure was at 88.7% at 3 years and was not related to preoperative volume. SAVER is a safe and effective procedure for treating the remodeled dilated anterior ventricle following anterior myocardial infarction.

Adult↗
PubMed2001

Effects of the Dor procedure on left ventricular dimension and shape and geometric correlates of mitral regurgitation one year after surgery.

OBJECTIVES: In the present study we retrospectively analyzed ventriculographic data from symptomatic patients after myocardial infarction who underwent the Dor procedure (endoventricular circular patch plasty repair) to evaluate left ventricular shape 1 year after the operation and to analyze the geometric correlates of late mitral regurgitation. METHODS: Forty-four patients with previous transmural anterior myocardial infarction comprised the study group. Left ventricular volumes, global left ventricular systolic and diastolic sphericity, the extent of wall motion abnormalities, and the presence and degree of mitral regurgitation were analyzed before and 1 year after operation. RESULTS: Comparing preoperative diastole to systole within the cardiac cycle, left ventricular shape becomes more elliptical in systole than it was in diastole (eccentricity index closer to 1). The intervention leads to an increased diastolic sphericity, but for each cardiac cycle, the systolic shape is more elliptical relative to its diastolic counterpart in respect to basal conditions. Mitral regurgitation was detected after operations in 17 patients; 14 of them did not have mitral regurgitation before operations. Patients with late mitral regurgitation had greater preoperative volumes and more spherical chamber than did patients without late mitral regurgitation. CONCLUSIONS: Despite a more spherical postoperative left ventricular chamber, systolic pump function improves after the Dor procedure, mainly for the improvement in inferior wall shortening. The presence of late mitral regurgitation is relatively frequent in this series of patients, and this emphasizes the importance of a more accurate quantitative evaluation of preoperative functional mitral regurgitation to repair the valve when appropriate. Geometric correlates of late mitral regurgitation appeared to be greater chamber sphericity and larger ventricular volumes preoperatively.

Angiography↗
PubMed2000

A plausible mechanism of electron transfer between quinones in photosynthetic reaction centers.

The mechanism of long-range electron transfer between the primary and the secondary quinone of photosynthetic reaction centers has been investigated, with particular attention on the role of the iron-histidine bridge. Computations suggest that in such a system, where the molecular subunits are packed together by H-bonds, a mobile electron, injected on one end of the chain, can be carried to the other end by switching the positions of the H-bonded hydrogens. Energy estimates would suggest that the proposed mechanism is plausible and worthy of further experimental investigations.

Animals↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor and interleukin-3 cause basophil histamine release by a common pathway: downregulation by sodium.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) are recognized as enhancers, but not as inducers, of histamine release from normal human basophils. However, when extracellular Na+ is removed IL-3 acquires the capacity to induce histamine release. The aim of this study was to evaluate whether GM-CSF can induce basophil histamine release using the same pathway of IL-3. Leucocyte suspensions from normal human subjects were stimulated with GM-CSF, IL-3 and anti-IgE, and histamine release was evaluated by an automated fluorometric method. In a physiological medium, GM-CSF (10 ng/ml) and IL-3 (10 ng/ml) did not provoke histamine release, in spite of an efficient response to anti-IgE (10 micrograms/ml). However, when extracellular Na+ was substituted iso-osmotically with N-methyl-d-glucamine+ or with choline+, GM-CSF and IL-3 were able to trigger histamine release from either mixed leucocyte suspensions or purified human basophils. The effect of GM-CSF on basophil histamine release was dose dependent, with optimal release at a dose of 1 ng/ml after incubation at 37 degrees for 60-120 min. The kinetics of IL-3-induced histamine release were similar, whereas anti-IgE-induced histamine release was more rapid, being almost maximal after incubation for 30 min. A good correlation was found between GM-CSF-induced and IL-3-induced histamine release; furthermore, the combined effects of the two cytokines were less than additive, suggesting that they share the same pathways leading to histamine release. When extracellular Na+ concentration was increased from 0 to 140 mm, histamine release induced by GM-CSF, IL-3 and anti-IgE was reduced progressively. In contrast, histamine release induced by these stimuli was upregulated when the concentration of extracellular Ca2+ was increased. These results provide indirect evidence that GM-CSF and IL-3 can induce basophil histamine release by a common pathway that is downregulated by Na+.

Adult↗
PubMed1999

Effects of reconstructive surgery for left ventricular anterior aneurysm on ventriculoarterial coupling.

OBJECTIVE: To investigate left ventricular elastance (Emax) and effective arterial elastance (Ea) in postinfarction left ventricular aneurysm and evaluate their role in left ventricular function improvement after endoventricular circular patch plasty (EVCPP). Ventriculoarterial coupling has never been studied in these patients. PATIENTS: 22 consecutive patients (49 to 73 years) with left ventricular anterior aneurysm. METHODS: Haemodynamic studies were done before and two weeks after EVCPP. Ventriculography was performed during atrial pacing (100 beats/min). Pressure/volume loops were analysed and derived parameters measured. Emax was estimated by applying the "single beat" method. Ea was calculated as end systolic pressure/stroke volume. RESULTS: Left ventricular volumes and Ea decreased after surgery: end diastolic volume index from mean (SD) 155 (53) to 106 (29); end systolic volume index from 112 (51) to 62 (30) ml/m2 (both p < 0.0001); Ea from 1.65 (0.70) to 1.39 (0.41) mm Hg/ml (p = 0.04). Ejection fraction and Emax increased, without significant changes in stroke volume and work. The decrease in Ea was directly correlated with its preoperative value. The time interval between left ventricular pressure upstroke and peak systolic pressure decreased, from 237 (39) to 191 (41) ms (p < 0.0001), paralleling morphological changes in pressure tracings. CONCLUSIONS: After EVCPP, ventriculoarterial coupling improves because of the fall in Ea caused by end systolic pressure reduction. The improvement is related to aortic pressure waveform changes and improved relaxation.

Aged↗
PubMed1998

Efficacy of endoventricular patch plasty in large postinfarction akinetic scar and severe left ventricular dysfunction: comparison with a series of large dyskinetic scars.

BACKGROUND: Many believe that dyskinesia is the only predictor of favorable surgical outcome after large myocardial infarction and that akinetic scars do not recover well in patients with globally depressed ventricular function. METHODS: This study evaluates clinical and hemodynamic results of endoventricular circular patch plasty in patients with either large akinetic scar (n = 51) or large dyskinetic scar (n = 49) and depressed left ventricular function (ejection fraction <30%). Groups were comparable for symptoms, indication for operation, and delay from myocardial infarction. Heart failure was a major indication for operation in both groups. Coronary grafting was performed in 98% of patients: 10 had mitral valve repair or replacement, and 47 patients with preoperative ventricular arrhythmias had cryotherapy. In-hospital mortality was 12% (five patients in the akinetic group [10%] and seven in the dyskinetic group [14%]). RESULTS: Results showed an early and late improvement in New York Heart Association functional class and ejection fraction (from 23% +/- 5% to 31% +/- 11% to 40% +/- 13% in akinetic patients and from 23% +/- 6% to 41% +/- 10% to 41% +/- 12% in dyskinetic patients). Ventricular tachycardia was reduced significantly in both groups early and late after the operation. CONCLUSION: We conclude that in patients with either large akinetic or dyskinetic scar and severe left ventricular dysfunction, endoventricular circular patch plasty associated with coronary grafting and cryotherapy, when indicated, provides surviving patients with significant improvement in cardiac function. This approach can be considered as an alternative to heart transplantation in patients with severe left ventricular dysfunction.

Cardiac Output↗
PubMed1997

Akinetic versus dyskinetic postinfarction scar: relation to surgical outcome in patients undergoing endoventricular circular patch plasty repair.

OBJECTIVES: This retrospective study attempted to relate surgical outcome with the extent and type of preoperative wall motion asynergy in patients with postinfarction myocardial scar who underwent endoventricular circular patch plasty repair and associated coronary grafting. BACKGROUND: Left ventricular (LV) pump function improvement is difficult to predict after aneurysmectomy, for either akinetic or dyskinetic scar, and previous studies have reported that the absence of paradoxic systolic motion correlates with higher operative mortality and no improvement in pump function. METHODS: Two hundred forty-five patients who underwent endoventricular circular patch plasty repair and associated coronary grafting were retrospectively selected if they had technically adequate right and left anterior LV angiograms before the operation. All had right and left cardiac catheterization. The centerline method was applied to preoperative right anterior oblique LV angiography to assess the absolute motion of the chords and the percent length of the perimeter showing a fractional shortening <2 SD from the normal mean value (extent of asynergy ([A%]). RESULTS: The overall perioperative mortality rate was 6%; 120 patients had akinetic and 125 had dyskinetic scar, and no differences were found among the groups in terms of all the clinical and hemodynamic variables collected in the study. Patients with a large scar (A% >60), either akinetic or dyskinetic, had a higher perioperative mortality rate (12%) than patients with a small scar (2.2%). After the operation, the ejection fraction (EF) increased from 36 +/- 13% to 50 +/- 13% (mean +/- SD), and pulmonary pressures significantly decreased. End-diastolic volume decreased from 199 +/- 75 to 89 +/- 36 ml/m2. Patients with a large akinetic scar had the most severely impaired preoperative function (largest ventricular volumes and highest pulmonary mean pressure); nevertheless, they had an impressive improvement in function (EF from 25 +/- 9% to 41 +/- 12%), not different from that observed with large dyskinetic scarring (EF from 26 +/- 7% to 46 +/- 11%). CONCLUSIONS: Surgical outcome of endoventricular circular patch plasty repair for postinfarction myocardial scar relates to the extent of LV asynergy rather than to the presence or absence of dyskinesia. Patients with a large akinetic scar and severely depressed pump function benefit from a relatively simple surgical procedure previously reserved only for dyskinetic aneurysm. The reduction of wall tension and oxygen demand, owing to the marked decrease of volumes, and the increase in oxygen supply, owing to revascularization, may play a major role in improving pump function.

Aged↗
PubMed1997

Ventricular remodeling in coronary artery disease.

Analyzing 16 recent (1993 to 1997) references devoted to left ventricular aneurysm or wall motion abnormality after myocardial infarct, it appears that 1) cardiologists are on their way to detecting earlier the bad evolution of left ventricular geometry after myocardial infarct, 2) a great number of cardiac surgeons are using the technique of left ventricular reconstruction with circular reorganization of the left ventricular cavity, very often by endoventricular patch; and 3) this advance leads to a modification in the indications for surgery for left ventricular aneurysms or akinesia, either to prevent progressive dilatation, or to improve some apparently hopeless old and large akinesias.

Cardiac Surgical Procedures↗
PubMed1995

Outcome of left ventricular aneurysmectomy with patch repair in patients with severely depressed pump function.

To determine the efficacy of left ventricular (LV) aneurysm resection and endoventricular patch repair with septal exclusion in patients with severely depressed pump function, we retrospectively selected 62 patients (mean age 59 +/- 7 years) with preoperative LV ejection fraction < or = 20%, from a series of 322 patients with postinfarction LV aneurysm who underwent this type of surgery at our center during a 5-year period. Mean ejection fraction was 17 +/- 3%; all patients were in New York Heart Association (NYHA) class III/IV, and all had hemodynamic and electrophysiologic studies before and after surgery. We analyzed both operative and long-term survival, and hemodynamic, electrophysiologic, and angiographic variables, as well as the symptomatic state after surgery. Follow-up was available in all patients (mean 23 +/- 14 months). Subtotal endocardiectomy and cryotherapy were associated in patients presenting with spontaneous or inducible ventricular arrhythmias (VA). Hospital mortality rate was 19.3%. Ejection fraction improved from 17 +/- 3% to 37 +/- 10% (p < 0.001); ventricular arrhythmias decreased significantly after surgery. Factors influencing early mortality at multivariate analysis were the presence of critical lesions on the circumflex artery and the duration of cardiopulmonary bypass. At 1-year control, a significant reduction in NYHA class was observed and no patient was in NYHA class IV. The improvement in ejection fraction was maintained (39 +/- 11%), as well as the reduction in inducible and spontaneous ventricular arrhythmias. There were 5 late deaths at follow-up, accounting for a late mortality of 10% at 5 years.

Aged↗