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Biomedical subjects

E Bonacina

Publications and source records attributed to E Bonacina.

At least 19 recordsLinked to original sources

Massive haemoptysis after living donor liver transplantation.

A 27 year old man with hereditary haemorrhagic telangiectasia who developed progressive liver dysfunction underwent living related right lobe transplantation. Pulmonary arteriography did not reveal arteriovenous malformation or abnormal intrapulmonary venous channels. The postoperative course was characterised by persistent hypoxaemia and respiratory failure developed. On day 6, a massive haemoptysis developed and the patient died shortly thereafter. The native liver showed a nodular pseudocirrhotic transformation, with highly dilated and irregularly interconnected vein-like or arterial-like structures in the fibrous septa. Pathological examination of both lungs showed irregular thickening of the wall of the arteries, secondary to eccentric and/or concentric myointimal hyperplasia. This case suggests that massive haemoptysis can develop even when arteriovenous malformations are undetectable by pulmonary arteriography, and it questions the role and the appropriateness of living donor liver transplantation in high risk patients.

Adult↗

Kaposi's sarcoma in liver transplant recipients: morphological and clinical description.

The clinical course and outcome of 5 adult patients who underwent orthotopic liver transplantation (OLT) and developed Kaposi's sarcoma (KS) is reported. From October 1986 to July 2000, a total of 459 patients underwent 499 OLTs at our hospital. The immunosuppressive regimen consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Tacrolimus was administered only in selected patients. Five patients developed KS, and the pathological diagnosis was established months 9 to 23 after OLT. Four of 5 patients died of KS, surviving 0 to 6 months after pathological diagnosis. The fifth patient, with KS confined to the skin, is disease free 6 months after diagnosis. All patients were treated with reduction of immunosuppressive therapy and/or chemotherapy. Retrospective molecular investigation by polymerase chain reaction for human herpesvirus type 8 DNA detected specific viral sequences in histological specimens of tissues involved by KS. In our experience with adult liver transplant recipients, we registered a slightly lower prevalence of KS compared with other reported data, but observed a high rate of graft involvement and mortality.

Adult↗

Low nitric oxide values associated with low levels of zinc and high levels of cardiac necrosis markers detected in the plasma of rabbits treated with L-NAME.

Nitric oxide plays a key role as a vasodilating agent and its deficiency is associated with ischemic heart diseases. The aim of this study was to induce biochemical alterations associated with ischemic heart lesions by blocking nitric oxide synthase. L-NAME, a nitric oxide synthase inhibitor, was administered to rabbits and its effects on blood pressure, plasma levels of nitric oxide, zinc and cardiac necrosis markers, heart histology, and electrocardiographic profile were examined. L-NAME administration reduced the nitric oxide levels and consequently increased the diastolic blood pressure. It also caused small areas of myocardial coagulative necrosis, whose dispersed nature made it undetectable by electrocardiograph, and decreased the plasma levels of zinc, which is involved in the enzymatic activities that remove the peroxides damaging the myocardium. This model is proposed for the development of drugs affecting nitric oxide levels with the aim of controlling coronary ischemia.

Animals↗

Adjunctive thrombus aspiration and mechanical protection from distal embolization in primary percutaneous intervention for acute myocardial infarction.

Primary percutaneous intervention for acute occlusion of a native coronary artery may be complicated by distal embolization of plaque or thrombotic debris, with infarct extension. We tested the clinical application of a new therapeutic strategy combining maximal antiplatelet therapy, with glycoprotein IIb/IIIa inhibition, and adjunctive mechanical protection from distal embolization and direct aspiration of thrombus with a new balloon and catheter system (PercuSurgetrade mark). Successful aspiration of thrombus could be obtained in 7 out of 8 attempted procedures, with inability to negotiate the angulated take-off of the circumflex coronary artery in one patient. The current mechanical characteristics of the device, primarily developed for use in larger saphenous vein grafts, and certain caveats and limitations are discussed. New dedicated systems should be available in the near future for the native coronary circulation. Excellent immediate angiographic results were obtained in all treated patients, without evidence of loss of distal branches and no intraprocedural complications.

Abciximab↗

Validation of a high performance liquid chromatographic method for alpha amanitin determination in urine.

The objective of the present study was to develop and validate a liquid chromatographic method with electrochemical detection to measure alpha amanitin concentrations in urine after sample pretreatment with double mechanism (reversed phase/cation exchange) solid-phase extraction cartridges. The urine samples (10 ml) were purified and concentrated to 1 ml with elimination of matrix contaminants. The extracts were then separated by isocratic reversed-phase chromatography using a C18 column (4.6 mm x 25 cm) with a mobile phase composed of 0.005 M phosphate buffer (pH 7.2) and acetonitrile (90:10). Coulometric detection was performed by applying an oxidation potential of +500 mV to a porous graphite electrode in a low-volume analytical cell. The limit of quantitation was 10 ng/ml with a signal-to-noise ratio = 25. The linearity studied on spiked urine was satisfactory (r = 0.9966) from 10 ng/ml to 200 ng/ml. The average extraction recovery of alpha amanitin was 78%, determined using spiked urine samples ranging from 10-300 ng/ml. The intra-assay precision was checked at 10, 50 and 100 ng/ml levels (n = 10) in spiked urine samples, with resulting coefficients of variation of 3.6%, 2% and 1.5%, respectively.

Amanitins↗

A semiquantitative approach to the evaluation of acute cardiac allograft rejection at endomyocardial biopsy.

BACKGROUND: Histopathologic criteria for grading of acute cardiac allograft rejection are focused on the most severe lesion that is recognized among the myocardial fragments provided by each endomyocardial biopsy specimen. Considering the distribution of rejection lesions among all the fragments improved the accuracy in characterizing the severity of rejection in pathologic studies. This study was undertaken to verify the usefulness of a semiquantitative evaluation of endomyocardial biopsy specimens, consisting of the calculation of the proportion of fragments showing rejection in the clinical setting. METHODS: Of the 2386 biopsy specimens obtained during the first posttransplantation year in 168 consecutive cardiac allograft recipients, 290 biopsy specimens constituted by > or = 3 adequate fragments and showing rejection not followed by treatment (n = 159) or being the first biopsy specimen prompting treatment with augmented immunosuppression for that rejection episode (n = 131) were selected. These biopsy specimens (index biopsy specimens) were grouped according to whether rejection was present in < or = 33%, > 33% to < or = 67%, and > 67% of the fragments. The rejection grade (according to the standardized grading system) and the proportion of fragments positive for rejection were correlated with the occurrence of clinical symptoms and signs of rejection at index biopsy and with the results of the next biopsy. RESULTS: Rejections graded > or = 3A were more frequently symptomatic (36% vs 9% for those graded < 3, p < 0.0001), as were those involving increasing proportions of fragments (< or = 33%: 5 of 124, 4%; > 33 to < or = 67%: 13 of 99, 13%; > 67%: 19 of 67, 28% [p < 0.0001]). Spontaneous resolution after untreated biopsies was more frequent in focal (grade 1A and 2) than in diffuse mild (1B) rejections (68% vs 38% [p < 0.04]), whereas progression to grade 3A or greater was less frequent (4% vs 27% [p < 0.01]). Increasing proportions of positive fragments were associated with lower frequencies of spontaneous resolution (p < 0.05) and higher frequencies of worsening (9%, 22%, 43% [p < 0.009]) or progression to grade 3A or greater (2%, 6%, 28% [p < 0.005]). Complete resolution after treatment was less frequent for increasing proportions of positive fragments at index biopsy (80%, 66%, 49% [p < 0.05]). CONCLUSIONS: Diffuse versus focal rejection pattern and the proportion of positive fragments seem to be clinically relevant in terms of occurrence of symptoms, spontaneous evolution, and response to treatment.

Adolescent↗

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.

Bacterial Infections↗

Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart.

Conditions of diastolic overload associated with increases in filling pressure trigger apoptosis. Moreover, ischemia alone and ischemia followed by reperfusion induce programmed cell death in myocytes in vitro. On this basis, the possibility was raised that apoptotic myocyte cell death may occur in the surviving myocardium acutely after infarction. Myocardial samples were obtained from the region adjacent to and remote from infarction in patients who died within 10 days from the initial clinical symptoms. Apoptosis was measured quantitatively by the terminal deoxynucleotidyl transferase assay and confirmed biochemically by DNA extraction and agarose gel electrophoresis. This analysis included 20 infarcted and ten control hearts. DNA strand breaks in myocyte nuclei were observed in all 20 infarcted hearts in both the regions bordering on and distant from the necrotic myocardium. However, the number of apoptotic nuclei was greater in the peri-infarcted region than in that away from infarction. Quantitatively, 12% of myocytes in the border zone showed DNA strand breaks, whereas 1% of cells were undergoing apoptosis in the remote myocardium. Moreover DNA laddering was detected biochemically in these two regions of the heart. Thus, apoptosis appears to be a significant complicating factor of acute myocardial infarction increasing the magnitude of myocyte cell death associated with coronary artery occlusion.

Adult↗

Significance of pericardial effusion after heart transplantation.

The aim of this study was to evaluate the clinical significance of pericardial effusion after heart transplantation and to assess its correlation with acute rejection. One hundred fifty transplanted patients were followed up for the first year: serial echocardiographic studies were performed on the same day as were the endomyocardial biopsies; hemodynamic studies and coronary angiographies were performed 1 year after transplant. Ten days after surgery, pericardial effusion was absent in 77 patients, small in 52, moderate in 14, and large in 7, and was significantly related to severe postoperative bleeding (p < 0.001). Patients were classified according to the presence and the course of pericardial effusion in group A (absence or disappearance of previous pericardial effusion within 1 month, 107 patients) and in group B (onset, persistence, or increase in pericardial effusion, 43 patients). One hundred nineteen patients experienced > or = 1 acute rejection episode. The evolution of pericardial effusion was different (p < 0.0001) according to the number of acute rejection episodes and biopsy specimens showing acute rejection, histologic grading and time of the first episode, and histologic grading of the most severe acute rejection episode. Furthermore, there was a significant correlation with the cumulative duration of acute rejection episodes (p < 0.005) and the presence of previous cardiac surgical history (p < 0.007), but no correlation with cardiac transplant vasculopathy or with a positive weight mismatch. This study suggests that pericardial effusion in transplant recipients is associated with a higher incidence and more severe histologic grading of acute rejection episodes; its presence indicates the need for stricter monitoring of acute rejection.

Acute Disease↗

Papillary fibroelastoma of the mitral valve. A rare cause of embolic events.

A 66-year-old woman was admitted to our department with an 11-month history of multiple transient ischemic attacks and strokes. A 2-dimensional echocardiographic study revealed an intracardiac tumor attached both to the chordae and to the anterolateral papillary muscle of the mitral valve. The patient underwent excision of the tumor, which necessitated concomitant mitral valve replacement. She remains free of symptoms 1 year postoperatively, with no echocardiographic evidence of recurrence of the tumor. To date, 19 cases of surgically treated papillary fibroelastomas of the mitral valve have been reported in the English-language literature. We add the description of our case to emphasize the importance of this tumor as an identifiable and curable cause of cerebral and coronary embolization. The frequent occurrence of cardiac valve tumors suggests the use of 2-dimensional echocardiography in patients who are experiencing transient ischemic attacks or strokes, as well as in those who sustain a myocardial infarction despite normal coronary arteries at angiography. When papillary fibroelastoma is diagnosed, surgical treatment must be considered because of the high risk of embolization.

Aged↗

Acute rejection after heart transplantation: noninvasive echocardiographic evaluation.

OBJECTIVES: The purpose of this study was to assess the reliability of echocardiography in the noninvasive diagnosis of acute rejection in heart transplant recipients. BACKGROUND: Although echocardiographic results seem to correlate well with allograft rejection, published data are limited and contradictory. METHODS: In 130 transplant recipients, 1,400 serial echocardiograms were recorded within 24 h of endomyocardial biopsy. Increased wall thickness, myocardial echogenicity, pericardial effusion, shorter pressure half-time, isovolumetric relaxation time and a decrease in left ventricular ejection fraction were considered markers of rejection. RESULTS: The distribution of echocardiographic markers revealed highly significant differences between bioptically graded moderate, mild and no rejection and between untreated and treated rejection episodes (both chi-square test, p < 0.0001). Specificity was 98.6% for two markers, but sensitivity was good (80%) for only moderate rejection because of the large number of false negatives in untreated patients with mild rejection. In untreated patients, there was a highly significant difference in the number of echocardiographic criteria between a benign and nonbenign outcome (chi-square test, p < 0.0001). In treated patients, the significant difference in the variation in echocardiographic criteria between favorable and unfavorable responses after 1 week was more pronounced after 2 weeks (t test, p < 0.01 vs. < 0.001). Diastolic indexes and pericardial effusion at 2 weeks seemed to be predictive of therapeutic response. CONCLUSIONS: Poor sensitivity to mild rejection indicates that serial echocardiography cannot supplant endomyocardial biopsy in the early diagnosis of acute rejection, but it seems to be a reliable noninvasive means of identifying acute rejection requiring intensified immunosuppressive therapy and of evaluating outcome.

Acute Disease↗

When and why do heart transplant recipients die? A 7 year experience of 1068 cardiac transplants.

This mortality study deals with the 1068 heart transplants (1054 patients) performed in Italian Units from November 1985 to April 1992. The death rate was 19.7% and the actuarial survival was 89% at 1 month, 83% at 1 year and 74% at 6.5 years. Recipients who died had been less often transplanted for dilated cardiomyopathy, were older (44.1 vs. 41.7 years) and more often male (84.5 vs. 72.7%). Analysis of the causes of death was restricted to orthotopic transplantations (1029/1068 procedures, 195/208 deaths). Deaths were grouped within four intervals: peri-operative (< or = 1 month, 50.0% of deaths), early (> 1 month < or = 3 months, 17.2%), intermediate (> 3 months < or = 2 years, 22.6%) and late (> 2 years, 10.2%). The prime causes of death were mostly postoperative graft failure (whose effects brought about 64% of peri-operative deaths, 28% of early and 7% of intermediate deaths), post-operative complications (10% of peri-operative deaths), acute rejection (10% of total deaths, distributed in all the periods), graft arteriopathy (6% of early, 36% of intermediate and 58% of late deaths), infections (17% of deaths, occurring in all periods but late) and malignant tumours (7% of deaths), lymphomas being the first to occur and Kaposi's sarcoma occurring only in the intermediate period. Repeat transplantation had a poor outcome (death rate 71.4%), two-thirds of the re-transplanted patients' deaths being due to early graft failure and a third to late relapsing graft vasculopathy.

Adult↗

[The contribution of pathology sections to the Italian Heart Transplant Project in the first 5 years of its activities (1985-1990)].

All the transplantation units within the Italian Heart Transplantation Project are supported by a section of pathology, devoted to the study of the recipient's heart, to patient monitoring by means of a schedule of endomyocardial biopsies, and, if that was the case, to examine the donor's heart and to analyse the causes of death. When successes and failures of the first five years of the Project's activity are weighed up, good results are observed: of the 847 operations performed (orthotopic, heterotopic and heart-lung transplants, and re-transplants) an actuarial survival rate of 77% at 5 years has been achieved. The sections of pathology believe to have contributed significantly to these results, examining as many as 10,446 endomyocardial biopsies. The indications for transplantation were: dilated cardiomyopathy (48.5%); ischemic (35.3%); valvular (5.9%) and congenital (2.4%) heart disease; hypertrophic cardiomyopathy (2.2%); endocardial fibroelastosis (1.7%); restrictive cardiomyopathy (1.4%); anthracycline cardiotoxicity (0.8%); myocarditis (0.8%); cardiac tumours (0.5%) and arrhythmogenic cardiomyopathy (0.2%). Distribution of recipients by sex and age varied according to the indications for transplantation: males were more common among the patients transplanted for ischemic (97%) and valvular (84%) heart disease, as well as for dilated (82%) and hypertrophic (78%) cardiomyopathy, whereas the opposite was true for endocardial fibroelastosis (males constituting 21%) and cardiac tumours (25%). Mean age at transplantation ranged from 49 years (ischemic heart disease) to 6 years (endocardial fibroelastosis). In the follow-up period, a 17.5% death rate was recorded; the main causes of death were the early failure of the transplanted heart (27 pts), postoperative complications (16), hyperacute rejection (4), acute rejection (18), infections (the singular most frequent cause of death, 35 pts), the proliferative endoarteritis of coronary branches (the so-called chronic rejection, that caused 21 deaths and required 14 re-transplants) and the development of neoplasms (11). The actuarial survival curve drops to 89% after the first postoperative month, abates to 82% at the end of the first year, and progressively decreases to 77% at the end of the fifth follow-up year. Rejection monitoring required an average number of 12.5 endomyocardial biopsies per recipient, and allowed 1.7 rejection episodes per patient to be diagnosed. The fewer were the rejection episodes occurring in a unit, the higher was the percentage of deaths due to infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Postpartum coronary artery dissection followed by heart transplantation.

A rare case of coronary artery dissection was observed in a 33-year-old woman on the fourth postpartum day. The ischemic syndrome was followed by aneurysmal dilatation of the left ventricle and progressive heart failure that necessitated cardiac transplantation. The patient is alive and well 3 years after the transplantation.

Adult↗