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.     

Transcriptional down-regulation of myogenin expression is associated with v-ras-induced block of differentiation in unestablished quail muscle cells

This study examined the distribution of muscarinic acetylcholine receptor-immunoreactive neurons in the amygdaloid complex of the rat, with emphasis on the central nucleus. The monoclonal antibody M35 raised against purified muscarinic acetylcholine receptor protein was used to visualize muscarinic acetylcholine receptor-immunoreactive cells. Muscarinic acetylcholine receptor immuno-reactivity was high in the central nucleus and low to moderate in all other regions of the amygdaloid complex. Within the central nucleus, the muscarinic acetylcholine receptor-immunoreactive neurons were found predominantly in the lateral subdivision. This region contained medium-sized neurons (largest diameter ranging from 10 to 15 microns), with a round or slightly ovoid cell shape. At the subcellular level, however, the labeled neurons revealed relatively few muscarinic acetylcholine receptor-immunoreactive postsynaptic densities. Immunofluorescent double-labeling demonstrated that nearly all of the muscarinic acetylcholine receptor-immunoreactive neurons (98.6%) in the central nucleus expressed abundant amounts of nicotinic acetylcholine receptors, further substantiating the cholinoceptive character of these cells. In addition, the vast majority of these muscarinic acetylcholine receptor-immunoreactive neurons (94.3%) were GABAergic neurons. The muscarinic acetylcholine receptor-immunoreactive neurons expressed moderate levels of protein kinase gamma, one of the likely intracellular mediators between muscarinic acetylcholine receptors and their elicited physiological response. The number and staining intensity of muscarinic acetylcholine receptor-immunoreactive neurons in the central nucleus varied dramatically among rats. This individual variation correlated positively with the rat's expression of conditioned immobility and correlated negatively with active shock avoidance performance. These results suggest that the GABAergic/cholinoceptive neuronal elements in the central nucleus are involved in the expression of fear-induced behaviors. This interpretation is further elaborated in a forthcoming paper.     

Quantitative determination of physical and chemical measurands in honey by near-infrared spectrometry

Fourier transform near-infrared spectroscopy (FT-NIR) was evaluated to quantitatively determine 24 different measurands in honey. The reference values of 421 honey samples of different botanical origins were determined by classical physical and chemical methods. Partial least squares regression was used to develop the calibration models for the measurands studied. These calibrations were then validated using independent samples and proved satisfying accuracies for the determination of water (standard error of prediction: 0.3 g/100 g), glucose (1.3 g/100 g), fructose (1.6 g/100 g), sucrose (0.4 g/100 g), total monosaccharide content (2.6 g/100 g) as well as fructose/glucose ratio (0.09) and glucose/water ratio (0.12). The prediction accuracy for hydroxymethylfurfural, proline, pH-value, electrical conductivity, free acidity and the minor sugars maltose, turanose, nigerose, erlose, trehalose, isomaltose, kojibiose, melezitose, raffinose, gentiobiose, melibiose, maltotriose was poor and unreliable. The results demonstrate that near-infrared spectrometry is a valuable, rapid and non-destructive tool for the quantitative analysis of some measurands related to the main components in honey.     

Atrial mapping and radiofrequency catheter ablation in patients with idiopathic atrial fibrillation. Electrophysiological findings and ablation results

BACKGROUND: Knowledge of the electrophysiological substrates and the cure of atrial fibrillation (AF) is still unsatisfactory. The goal of this study was to evaluate the electrophysiological features of idiopathic AF and their relationship to the results of radiofrequency (RF) catheter ablation of AF and the safety and effectiveness of this procedure. METHODS AND RESULTS: Sixteen patients with idiopathic AF underwent atrial mapping during AF and then RF ablation in the right atrium. The atrial activation was simultaneously recorded in four regions in the right atrium: high lateral wall (HL), low lateral wall (LL), high septum (HS), and low septum (LS) and in the left atrium through the coronary sinus (CS). In these regions, we evaluated the atrial fibrillation intervals (FF) and the morphological features of AF recordings by Wells' classification. No complications occurred during RF ablation. Of the 16 patients, 9 (56%) without AF recurrences during the follow-up (11 +/- 4 months) were considered successfully ablated. These patients showed a significantly shorter mean FF interval in the HS and the LS (122 +/- 32 and 126 +/- 28 ms, respectively), than in the HL and LL (159 +/- 24 and 156 +/- 28 ms, respectively). Moreover, the septum had more irregular electrical activity with greater beat-to-beat changes in FF and a higher prevalence of type III AF than the lateral region. The CS had similar behavior to the septum. Conversely, patients with unsuccessful ablation had an irregular atrial activity in the lateral wall, septum, and CS with no significant differences between the different sites. CONCLUSIONS: Right atrial endocardial catheter ablation of AF is a safe procedure and may be effective in some patients with idiopathic AF. The atrial mapping during AF showed a more disorganized right atrial activation in the septum than in the lateral wall in patients with successful ablation.     

Identification of HLA-unrestricted CD8+/CD28- cytotoxic T-cell clones specific for leukemic blasts in children with acute leukemia

We report on the identification of 57 T-cell clones (TCC) cytolytic to autologous leukemic blasts (LB) but not autologous bone marrow remission cells. LB-reactive TCC were obtained from 3 children with acute leukemia at remission; all expressed the same phenotype, CD3/TCR alpha beta/CD8+, but were heterogeneous for the expression of V beta T-cell receptor (TCR) V region chains, thus showing that these cells were not derived from the expansion of a single clone. Cytolytic activity of LB-reactive TCC was not restricted to autologous LB because they were also able to lyse phenotypically similar allogeneic LB but not bone marrow remission cells of the same patients. Neither autologous nor allogeneic LB used in the present study as stimulator and target cells expressed CD80 (B7/BB-1) antigen, and LB-reactive TCC were CD28-. Cytolytic activity of the clones was only inhibited by anti-CD11a (LFA-1) mAb but not by mAbs specific for HLA class I and II, CD3, CD8, or TCR alpha beta. In conclusion, these data suggest that a subset of apparently HLA-unrestricted, CD3/TCR alpha beta/CD8+ CD28- cytotoxic T lymphocytes, which use a TCR/CD3-independent recognition pathway, is primarily involved in antitumor immune response of children with acute leukemia at remission, possibly contributing to the control of minimal residual disease.     

MUC6 expression in breast tissues and cultured cells: abnormal expression in tumors and regulation by steroid hormones

DIG-labelled sense and antisense cRNA probes were synthesized from cDNA clones of CymMV and ORSV for virus detection in infected plants. A slot-blot hybridization assay was developed using either crude leaf extracts or total RNA from infected leaves. The assay could detect 50 and 250 pg of purified CymMV and ORSV RNA, respectively. As little as 30 mg of Nicotiana benthamiana infected leaves was sufficient to provide positive detection. CymMV and ORSV were detected at 3125 and 625 times dilution of leaf extracts, respectively. The DIG-labelled cRNA probes are stable for more than a year. This method is sensitive, reliable and suitable for large-scale routine testing of plant viruses. By using the two DIG-labelled cRNA probes in situ, CymMV and ORSV were localized in systemically infected leaves and stems of N. benthamiana and orchids.     

Ophthalmoplegia-ataxia-areflexia in pediatrics. Three new patients and review of the literature

OBJECTIVE: The objective of this study was to investigate if pediatric patients with benign brainstem encephalitis (Bickerstaff Syndrome) or with Miller-Fisher Syndrome are the extremes of the same nosological entity which, in adults, has been named ophalmoplegia-ataxia-areflexia syndrome. PATIENTS AND METHODS: The subjects included in the study were three patients of our institution and 24 patients found in the revision of the English and Spanish pediatric literature who fulfilled the diagnostic criteria of ophtalmoplegia-ataxia-areflexia syndrome. The topographical location of the lesion in the nervous system was based on previously established criteria by using clinical and complementary studies. RESULTS: Of the 27 patients included in the study we were able to reach an accurate topographical diagnosis in 9. None had an exclusive involvement of the peripheral nervous system, (6) had exclusively central nervous system involvement and 2 showed involvement of both system. In 12, the topographical location of the lesion could be only ascertained as probable; 3 of them in the peripheral nervous system, 2 in the central nervous system and mixed involvement in 7. In the remaining 7 patients there were insufficient clinical data to allow topographical classification. CONCLUSIONS: The ophtalmoplegia-ataxia-areflexia syndrome can also be found in pediatric patients. The lesion in the majority of patients in this age group is located in the central nervous system, either alone or combined with peripheral nervous system involvement.