Myocardial protection in adult cardiac surgery: current options and future challenges

Current techniques of myocardial protection are evolving with the use of less conventional modalities of cardioplegia and have reduced the morbidity and mortality of cardiac operations. Blood cardioplegic solutions appear superior to cold cardioplegia in terms of myocardial protection and adjuncts as glutamate/aspartate enhancement, antioxidant supplementation, nitric oxide donors and maintenance of calcium homeostasis seem effective. In the near future, further experimental and clinical investigations about pharmacological preconditioning, sodium–hydrogen exchangers inhibition and gene therapy need to be addressed to well define their potential role in the improvement of current techniques of myocardial protection that are suboptimal in high-risk clinical settings.     

Early reconstruction of the abdominal wall in giant omphalocele.

Omphalocele is the most common congenital defect of the abdominal wall. Mortality rate is between 20 and 70% and early closure of the abdominal wall, within 10 days of life, is vital to the successful outcome of the surgical treatment. The authors describe the use of two bipedicled flaps of abdominal skin to correct the defect of the midline as soon as the reduction of all viscera has been accomplished.     

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy.     

Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity

Using short term CTL lines derived from HLA A2/K^b transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/K^b molecules. Interestingly, T cell recognition of the naturally processed form of the NS4.1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.     

Soluble Antiapoptotic Molecules and Immune Activation in Chronic Heart Failure and Unstable Angina Pectoris

Programmed myocyte cell death and activation of the immune system have been shown to occur in patients with congestive heart failure. Besides, unstable angina episodes are likely to be associated with immune activation. Our aim was to evaluate the role of changes in circulating levels of soluble Fas (sFas), suggestive of an enhanced inhibitory response to ongoing apoptosis, and soluble IL2 receptor (sIL2-R), indicative of T-lymphocyte activation, in chronic heart failure and unstable angina pectoris. Thirty patients affected by chronic heart failure (20 idiopathic and 10 ischemic cardiomyopathy) and 13 patients with unstable angina were evaluated. Twenty healthy individuals matched for age and gender were used as controls. A complete biochemical determination of indexes of myocardial damage including cardiac troponin I (cTnI) and creatine kinase (MB/CK) was performed. The results demonstrated that mean levels of sFas and sIL2-R were significantly increased in patients affected by chronic heart failure and unstable angina and were not associated with changes in renal function or with serum levels of cTnI. Highest values of sFas were found in NYHA class IV patients (IV NYHA class = 7.39 ± 0.52 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and more elevated in idiopathic than in ischemic cardiomyopathy (3.64 ± 0.40 vs. 1.82 ± 0.37 ng/ml; P < 0.01). Moreover, in chronic heart failure patients sFas and ejection fraction were negatively correlated (P = 0.01), whereas sFas and sIL2-R were positively correlated (P < 0.01). In unstable angina patients too, sFas and sIL2-R appeared to be correlated (P = 0.03); whereas sFas (angina group = 3.18 ± 0.39 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and sIL2-R (angina group = 0.46 ± 0.11 vs. controls = 0.00 UI/ml; P < 0.01) were higher in angina group than in controls. In most of the cases, the increase of sFas was associated with comparable changes in sIL2-R serum levels, indicating that the activation of Fas system is strictly associated with autoimmune–inflammatory reactions. This phenomenon, both in chronic heart failure and in unstable angina, occurs in the absence of biochemical evidences of myocardial damage and seems to parallel the activation of T cell. Soluble Fas could have a role in sustaining inflammatory response and in prolonging the detrimental effects correlated with it in chronic heart failure and angina pectoris.     

Exclusion of Treacher Collins Franceschetti syndrome in a subject with tetralogy of Fallot and cryptorchidism

Genotyping with flanking DNA markers was used to ascertain Treacher Collins Franceschetti syndrome (TCOF1) in a subject affected by tetralogy of Fallot and cryptorchidism. The proband's family consisted of a father and sister who were affected by the disease, and a healthy mother. Since cardiac malformation and cryptorchidism have been associated with the TCOF1 syndrome, the proband was suspected to be a carrier of the mutated gene. Microsatellite markers D5S527, SPARC and D5S519, which previously mapped the TCOF1 gene within a 2.1-cM interval on chromosome 5 (5q32–33.1), were used to follow the transmission of the TCOf 1 mutated locus. Flanking markers D5S519 and D5S527 were informative and enabled us to exclude inheritance of a TCOF1 mutation to the proband, while showing that cardiac malformation and cryptorchidism were unrelated in mis patient.     

Reproductive risk factors in unilateral and bilateral renal agenesis

ABSTRACT  Renal agenesis (RA) appears to be a multifactorial condition with combined genetic and environmental influences. We performed a retrospective case-control study of reproductive history of 26 isolated RA live births cases referred to Sicilian Registry of Congenital Malformations. A statistical significant association for birth weight if we considered all RA together and for bilateral RA alone, an increasing risk for maternal age only in the bilateral RA subgroup and a male predominance both for unilateral and bilateral RA was found. Our results show that some reproductive risk factors may be associated with RA, moreover differences found between subgroups indicate that some risk factors may be different in unilateral and bilateral RA. The association between reproductive risk factors and RA may reflect pathogenetic interaction between genetic and environmental factors. Nevertheless further studies are needed to clarify these associations and to explore the role of perinatal factors in the etiology of renal agenesis. In fact if prenatal or perinatal risk factors are in a causal chain influencing the risk for developing RA, then these data could have important implications in the prevention or treatment of this condition.     

Survival and prognostic indicators in compensated and decompensated cirrhosis

Six-year survival of cirrhosis was assessed in a series of 1155 consecutive patients (751 men, 404 women). Among the men, 33% were alcoholics and 18% were HB_sAg positive; corresponding figures for the women were 15% and 6%, respectively. Features of decompensation at first presentation were observed in 63% of the patients. Six-year survival was 54% in compensated and 21% in decompensated patients. No significant differences in survival were found between alcoholics and nonalcoholics. Leading causes of death were liver failure (49%), hepatocellular carcinoma (22%), and bleeding (13%). The prognostic role of 21 variables was evaluated separately in compensated and decompensated patients by the Cox's regression model. The following variables were found to be significant predictors of death risk in compensated patients: male sex, HB_sAg positivity, age, prothrombin time prolongation, and esophageal varices. In decompensated disease the significant indicators of death risk were: hepatocellular carcinoma, encephalopathy, hemorrhage, SGOT, esophageal varices, gamma globulins, prothrombin time prolongation, continued abuse of alcohol, HB_sAg positivity, gamma glutamyl transpeptidase, and cholinesterase. A simple prognostic index based upon the relative risk coefficient of the significant variables is suggested.Members of the Liver Study Group are: Maria Caltagirone, Gabriella Filippazzo, Giovanni Gatto, Gandolfo Giannuoli, Silvio Margin, Guiseppe Malizia, Lorenzo Maniaci, Maria Pia Marcenó, Alberto Maringhini, Rocco Micciolo, Salvatore Orsini, Fabio Pace, Ugo Palazzo, Linda Pasta, Giuseppina Russo, Rosa Giovanna Simonetti, Mario Spinello, Mario Traina, Mario Valenza, Maria Vinci, Giovanni Vizzini.     

Early prognosis of epilepsy. Effects of treatment in the first follow-up year

A multicenter prospective investigation was conducted in 17 teaching and general hospital in Italy to assess the efficacy of the care delivered to previously untreated patients with epilepsy. 175 cases were included and allocated to monotherapy. Only 112 cases completed the first year of follow-up. Of these, 59 (52.7%) were completely controlled and 53 (47.3%) had one or more seizure relapses. Controlied and uncontrolled patients were compared with respect to the main variables believed to influence non-responsiveness to standard therapy. The proportion of cases with relapses was significantly associated with the number of seizures reported before treatment was started. Selected seizure patterns (absences, myoclonic seizures) and prolonged disease duration were also reported more frequently among patients with recurrences. The implications of these findings are discussed with respect to drug response and prognosis of epilepsy.

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Sommario Il presente studio consiste in una indagine prospettica multicentrica condotta in 17 centri ospedalieri italiani sulla efficacia del trattamento e sulla prognosi della malattia in pazienti con epilessia alla prima diagnosi. Dei 175 casi ammessi allo studio, 112 hanno completato il primo anno di osservazione. Di questi, 59 (52,7%) risultavano completamente controllati e 53 (47,3%) avevano presentato una o più crisi durante il follow-up. Le principali variabili ritenute responsabili di una insoddisfacente risposta al trattamento vennero quindi esaminate nei due gruppi. Il rischio di recidiva di crisi risultava significativamente correlato al numero di crisi presentate prima del trattamento. Inoltre, i pazienti con crisi nel follow-up presentavano una maggior durata di malattia o specifici tipi di crisi (assenze, crisi miocloniche). Il significato di tali dati è discusso in riferimento alle modalità di trattamento e agli altri fattori implicati nella prognosi dell'epilessia.