Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Afterload mismatch-related problems after "domino" heart transplantation

The heart transplants with domino technique, which uses donor hearts from heart-lung recipients, increases the pool of donors, provides the advantage of shortening the ischemic time and makes suitable hearts for patients with pulmonary hypertension. The present study aimed to characterise the pre- and post-transplant clinical and hemodynamic profiles of patients that underwent domino transplant in Pavia. METHODS: Between 1991 and 1992, 9 heart transplants were performed with the domino procedure at I.R.C.C.S. Policlinico S. Matteo of Pavia. Domino donors (6 with primary pulmonary hypertension, 2 with Eisenmenger's syndrome due to atrial septal defect, 1 with cystic fibrosis) underwent electrocardiographic, echocardiographic, chest roentgenogram studies, and right heart catheterization and coronary angiography (for donor older than 40). Domino recipients, 6 males and 3 females with a mean age of 44 years, had dilated cardiomyopathy (4 cases), coronary artery disease (4 cases) and valvular heart disease (1 case) (group 1). Seven of the 9 cases entered the study; 2 were excluded: one because had undergone heterotopic transplantation, the other had received the heart from another country and therefore the graft had suffered from a very long ischemic time. Controls group consisted of 12 patients who had consecutively undergone cardiac transplantation with non-domino donors during the same period (group 2). Immunosuppression was similar in both groups, and consisted of a combination of cyclosporin A, azathioprine and corticosteroids, plus a 7-day-course of antithymocyte globulin. Hemodynamic and echocardiographic controls were performed at 2, 3 and 4 weeks (short-term control) and at 2 and 6 months (mid-term control) after surgery. RESULTS: Domino donors (39 +/- 12.5 years) had significantly higher mean right ventricular end-diastolic diameter and lower left ventricular diameter than normal mean values. Domino recipients had significantly higher mean pulmonary arteriolar resistances than controls; mean ischemic time was also significantly lower in group 1 than in group 2. Short- and mid-term controls after surgery in group 1 showed persistently higher systemic vascular resistances and pulmonary vascular resistances and lower cardiac output than in group 1. Two patients developed an early and unexpected increase in pulmonary wedge pressure accompanied by severe paroxysmal nocturnal dyspnea and mitral regurgitation. In all cases, the left ventricles were relatively inadequate; the combination of low cardiac output and of high systemic vascular resistances favoured the occurrence of an afterload mismatch condition that was worsened by chronic hypoxia. This condition must be known and expected in these patients after transplantation in order to provide timely and effective treatment to potentially life-threatening left ventricular failure episodes. IN CONCLUSION, the subset of transplanted patients that receives domino donors may develop left-side afterload mismatch which, combined with low cardiac output, with high systemic vascular resistances and with the effects of chronic hypoxia originally suffered by the heart, may cause sudden and unexpected left-side heart failure which has to be timely recognised and managed. Although hemodynamic adaptation of this patients is highly problematic, it does not limit the value of the domino procedure.     

On the numerical evaluation of Eshelby's tensor and its application to elastoplastic fibrous composites

A numerical evaluation of Eshelby's S tensor for an ellipsoidal inclusion imbedded in a general anisotropic matrix material is performed. The numerical scheme is valid for any degree of matrix anisotropy and for any aspect ratio of the ellipsoid, including the extreme cases of cracks and cylindrical inclusions. The influence of matrix anisotropy on the evaluation of S is tested extensively for cylindrical inclusions by considering plasticity induced anisotropy in the instantaneous properties of an elastic-plastic matrix material. The Mori-Tanaka averaging method is used to study the influence of the evaluation of S on the prediction of instantaneous effective properties of fibrous composites with elastic fibres and elastic-plastic matrix.     

Effects of castration on grooming in goats

In African antelope and North American cervids, breeding males during the rut engage in less oral self-grooming, and harbor a greater density of ticks, compared with conspecific females and non-breeding males. The purpose of this study was to experimentally test the proposition that down-regulation of self grooming in some male bovids occurs via the direct or indirect action of testosterone. Domestic dairy goats (Capra hircus) were used as a model. In Experiment 1, comparative observations conducted on twelve gonadally intact male goats (bucks), nine males castrated at 3 weeks of age (wethers), and twelve intact females (does) supported the prediction that the grooming rate of intact males would be depressed relative to wethers and does. Bucks oral groomed at one-third and one-fourth the rate of wethers and does, respectively, and they scratch groomed half as much as does. There was no significant difference between wethers and does in oral or scratch grooming rates. Experiment 2 involved castration of eleven bucks from Experiment 1, followed by 2 months of observation. Similar to the pattern of other testosterone-dependent behavioral changes after castration in adult males, there was a good deal of variation in the individual grooming response of males to castration, with increases in grooming taking 2 to 8 weeks to be manifested in ten of eleven goats. Overall, castrated males oral groomed about 3 x above their intact rates, supporting the prediction that castration removes testosterone-mediated suppression of grooming. This is the first example of alteration of grooming behavior in males by gonadal androgen, and the first demonstration of enhancement of any mammalian behavior by removal of gonadal androgen.     

Elastoplastic behavior of metal matrix composites based on incremental plasticity and the Mori-Tanaka averaging scheme

The applicability of the Mori-Tanaka averaging method for the prediction of the response of binary composites loaded in the plastic range is investigated. The applied loading is subdivided into small increments and the Eshelby solution for the inhomogeneity problem is used in conjunction with the Mori-Tanaka averaging scheme to obtain the load increments in the various phases. Since the Eshelby solution depends on the instantaneous matrix material properties and these are updated at the end of each load increment by using the backward difference scheme, an iterative procedure is necessary for the calculation of the correct load increments in the phases (concentration factors). The performance of the Mori-Tanaka method is compared with results obtained using the periodic hexagonal array (PHA) finite element model and experimental results for a B-Al unidirectional fibrous composite; it is also compared with numerical simulations obtained from the modified PHA model for a SiC _w -Al particulate composite.     

Ectopic anthocyanin pigmentation in maize as a tool for defining interactions between homologous regulatory factors

In the present paper, a nonlinear compartmental model for theophylline pharmacokinetics is developed. The analytical solution of the model, in parametric form, is derived under plateau conditions for plasma metabolite concentration. The parameters are obtained from plasma and urine data using best fitting techniques and their values are used in order to calculate maintenance intravenous infusion. Numerical simulation is then performed in order to compare the drug concentration obtained by our approach with that of alternative intravenous regimens. The differences argue for individualized dosage regimens, since theophylline is a drug with a narrow therapeutic window and its concentration at the active sites strongly depends on characteristic parameters of the patient's response. Our results show that it is possible to estimate the patients' parameters during the first 8 h after intravenous administration of the drug and these parameters can be used to design an individualized dosage regimen in patients receiving theophylline intravenously.     

On fumonisin incidence in monoculture maize under no‐till,conventional tillage and two nitrogen fertilisation levels

BACKGROUND: Fusarium ear rot and fumonisin contamination are serious problems for maize growers. The lack of maize genotypes highly resistant to fumonisin contamination emphasises the need for management strategies to prevent contamination by this mycotoxin. There are conflicting reports regarding no‐till and nitrogen (N) fertilisation practices in relation to the incidence of fumonisins. In this study the effect of no‐till compared with conventional tillage and of N fertilisation rates on fumonisin occurrence was investigated over three years in Northern Italy. RESULTS: The average contamination of grain by fumonisins B₁ and B₂ over the three years was significantly different, with a lower value in 2000 (516 µg kg^?1) than in the other years (5846 and 3269 µg kg^?1 in 2001 and 2002 respectively). Conventional tillage and no‐till treatments had no significant effect on the incidence of fumonisins. This finding suggests that above‐ground residues infected by Fusarium would not lead to an increase in fumonisin incidence. However, N fertilisation significantly increased fumonisin levels, by 99 and 70% in 2000 and 2001 respectively. CONCLUSION: Maize monoculture does not show a cumulative effect on the occurrence of fumonisins, while high rates of N fertiliser consistently result in elevated fumonisin levels. Both these effects can be influenced by annual meteorological fluctuations. Copyright © 2008 Society of Chemical Industry     

Investigation of defects in actinide-doped UO2 by positron annihilation spectroscopy

The nuclearization and validation of a new positron annihilation lifetime spectroscopy (PALS) system was ideally used to investigate vacancy defects generated by α self-irradiation in the UO₂ matrix of several plutonium-doped samples. The damage levels studied ranged from 0 to 0.3 dpa. This study validated the operational protocols for actinide-doped materials. A lattice lifetime of about 170–180 ps was determined for the undoped UO₂ matrix, which is consistent with the values reported in the literature. Alpha self-irradiation damage systematically increases the mean positron lifetime, resulting in a difference of 133 ps for a damage level of 0.3 dpa. Even at low damage values, a positron trapping site appears that corresponds to point defects involving an uranium vacancy, with a specific lifetime of about 310 ps. When annealed at 1373 K, some of these defects coalesce to form larger extended defects. The initial results for actinide-doped UO₂ also confirm the high sensitivity of PALS to the presence of vacancy defects even at low integrated α dose.     

Cerebral and pulmonary miliary tuberculosis in an immunocompetent patient: aggravation in an adequately treated patient

BACKGROUND: Extrapulmonary localizations are observed in 20% of tuberculosis cases, mainly in immunosuppressed patients. Prognosis is poor in case of relatively uncommon cerebral localizations and miliary dissemination, especially if treatment is initiated in late stages. We report a case of disseminated tuberculosis associated with cerebral and pulmonary localizations in an immunocompetent patient. THe disease progressed despite adapted treatment. CASE REPORT: A young immunocompetent man with an uneventful history developed miliary tuberculosis with pulmonary localizations visualized on the computed tomography (CT) of the thorax. Brain CT was normal, but magnetic resonance imaging revealed several intracranial lesions. The disease course was marked by development of neurological symptoms and progression of the cerebral lesions after one month of treatment. No evidence of therapeutic failure (insufficient dosing, non-compliance, primary resistance) could be identified. DISCUSSION: Magnetic resonance imaging provides a more precise evaluation of tuberculosis lesions in the brain. Early antituberculosis therapy associated with corticosteroids can improve prognosis. Clinicians should be aware that cerebral lesions may continue to progress despite appropriate treatment, a course which is not satisfactorily explained by any current pathogenic hypothesis.