Intrafamilial phenotypic variability in four families with Anderson-Fabry disease.

We analysed the clinical history of 16 hemizygous males affected by Anderson-Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from 26 to 61 years of age, died, whereas nine (age range 23-55) are alive. Eleven patients have undergone enzyme replacement therapy (ERT) for a period of 5-10 years. We have found a wide range of intrafamilial phenotypic variability in these families, both in terms of target-organs and severity of the disease. Overall, our findings confirm previous data from the literature showing a high degree of intrafamilial phenotypic variability in patients carrying the same mutation. Furthermore, our results underscore the difficulty in giving accurate prognostic information to patients during genetic counselling, both in terms of rate of disease progression and involvement of different organs, when such prognosis is solely based on the patient's family history.

Enzyme replacement therapy with agalsidase alfa in a cohort of Italian patients with Anderson-Fabry disease: testing the effects with the Mainz Severity Score Index.

Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by lysosomal storage of several glycosphingolipids, affecting virtually all organs and systems. Enzyme replacement therapy (ERT) for AFD has been available since 2001. Due to the highly variable nature of clinical manifestations in patients with AFD, it is very difficult to assess disease progression and the effects of therapy. We used the Mainz Severity Score Index (MSSI) as a measure of disease severity to study the effects of ERT in a population of 30 patients treated with agalsidase alfa for a median of 2.9 years (range, 1.0-6.2 years). Our data show that the MSSI captures the correlation between disease severity and both gender and age (1 - males performing worse than females at baseline and 2 - severity of diseases progresses with age in both sex). Furthermore, after at least 1 year of ERT, total MSSI scores were significantly lower than those at baseline (p < 0.001), suggesting a marked clinical improvement under ERT. In conclusion, the MSSI is a sensitive and useful tool for monitoring disease progression and assessing the effects of ERT in a population of patients from different treatment centres.

Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion.

OBJECTIVES: The study evaluated the role of the autonomic nervous system in atrial fibrillation (AF) recurrence. BACKGROUND: Early recurrence of AF after cardioversion (CV) is attributed to electrical remodeling. The possibility that an abnormal autonomic modulation might contribute to this phenomenon has not yet been adequately tested. METHODS: We analyzed short-term heart rate variability (HRV) in 93 patients with persistent AF and on chronic amiodarone treatment, after restoration of sinus rhythm by electrical CV. RESULTS: Two weeks later, 25 patients presented with AF. Spectral analysis of HRV revealed that patients wi

Left ventricular opacification by intravenous contrast echocardiography.

BACKGROUND: The present study was undertaken in order to evaluate the efficacy of the intravenous administration of Albunex in obtaining left ventricular opacification and the relationship between left ventricular opacification and pulmonary pressures and cardiac function. METHODS: Fifty-two adult patients, mostly affected by ischemic heart disease, were enrolled in the study. In 37 of these patients, a complete right heart hemodynamic study was performed after Swan-Ganz catheterization. Albunex was administered in three randomized doses (0.10, 0.15 and 0.20 ml/kg) to all the patients. Left ventricular opacification was assessed both visually and using videodensitometric analysis. RESULTS: Left ventricular opacification was obtained in 93% of all the injections and an intermediate or strong opacification was obtained in 68%, while absent opacification was observed in 6% of the injections, irrespective of the contrast dose. An incremental opacification efficacy trend was observed from the lower to the higher dose, with an intermediate or strong opacification in 58 and in 77% of 0.10 and 0.20 ml/kg injections, respectively. Irrespective of the contrast dose, an enhancement of the endocardial borders was observed in 61% of the wall segments suboptimally visualized in basal conditions. The endocardial borders enhancement was obtained in 39 and in 79% of segments using the 0.10 and the 0.20 ml/kg doses, respectively. No statistically significant differences were observed between the videodensitometric parameters obtained using the three contrast doses. Finally, a significant relationship was observed between left ventricular opacification parameters and pulmonary pressures and left ventricular functional parameters, irrespective of the contrast doses considered. CONCLUSIONS: The results we obtained demonstrate the good overall efficacy of Albunex administered intravenously in order to obtain left ventricular opacification in a clinical population of cardiac patients. Moreover, they suggest that the dosage to be used clinically should preferably be at least 0.20 ml/kg, although no significant influence of contrast dosage on videodensitometric parameters has been observed. Finally, irrespective of the contrast dosage, the magnitude of left ventricular opacification appears to be influenced by the hemodynamic status of the patient.

A single step density gradient separation for large scale enrichment of mobilized peripheral blood progenitor cells collected for autotransplantation.

Peripheral blood leukocytes are becoming the preferred source of hematopoietic progenitor/stem cells for autologous transplantation. However, in vitro purging procedures are complex and expensive when applied to peripheral blood progenitor cells harvests. This is mainly due to the large quantities of nucleated cells present in leukapheresis collections. Aiming to reduce total cellularity without significant loss of CD34+ cells, we developed an in vitro cell separation procedure based on ficoll/metrizoate gradient used at a final density of 1.067 g/ml. To obtain this density, standard Lympho-prep (1.077 g/ml) was diluted with normal saline solution (NaCl 9 g/l). Twenty-six leukapheresis collections (median cellularity 21.1 x 10(9), range 2.8-60) from 14 patients with non-Hodgkin's lymphoma, multiple myeloma or plasma cell leukemia were processed (median two leukaphereses per patient). Mean (+/- s.d.) recovery of total nucleated cells, CD34+ cells and CFU-GM was 20.9 +/- 10%, 74.7 +/- 22% and 70.5 +/- 19%, respectively. Cumulative per patient progenitor cell recovery was always above 50%, and as high as 80% in 10/14 patients, while total cellularity was reduced to a median 21.5% (10-33%) of pre-separation values. Contaminating neoplastic cells, identified by immunofluorescence in five collections, were reduced by 1-2 logs. The results indicate that our density gradient separation is an effective method to reduce total cellularity prior to immunological purging, without significant loss of progenitor cells.

Multiple myeloma: reduced plasma cell contamination in peripheral blood progenitor cell collections performed after repeated high-dose chemotherapy courses.

The possibility of reducing tumour cell contamination by cytotoxic drug courses prior to peripheral blood progenitor cell (PBPC) collection was evaluated in two consecutives groups of multiple myeloma (MM) patient candidates for autograft. All patients were at disease onset and received two VAD (vincristine, doxorubicin and dexamethasone) courses as initial debulking. In the first group (44 patients), mobilization and harvest were performed 'upfront', after a single cyclophosphamide (CY) administration of 4 g/m2; in the second group (17 patients), PBPC were collected at the end of a high-dose sequential chemotherapy programme, including: CY 5 g/m2, etoposide (VP16) 2 g/m2, a chemotherapy-free interval with three courses of high-dose dexamethasone, a final mobilizing CY at 7 g/m2. G-CSF was given following each high-dose cytotoxic drug. Cytofluorimetric analysis was performed to quantify progenitors (CD34+ cells) and plasma cells, identified by the high CD38 expression and/or CD38 and CD138 coexpression. Large amounts of PBPC were collected in either group (median harvested CD34+/kg: 15.8 x 10(6) and 13.4 x 10(6), respectively; P=0.9). Circulating plasma cells were significantly higher in patients mobilized 'upfront' compared to those who received the high-dose sequence (median peak values of CD38bright/microl: 39 and 10, respectively; P=0.02); a similar difference was observed in the amount of contaminating plasma cells in the harvest products (median CD38bright/kg: 7.4 x 10(6) and 1.3 x 10(6), respectively; P=0.02). The results demonstrate that an in vivo purging approach is feasible in myeloma patients through repeated high-dose chemotherapy courses; this may provide less-contaminated material suitable for further in vitro purging procedures.

[Late ventricular potentials in the post-infarct patient. A follow-up at 4 years]. / I potenziali tardivi ventricolari nel post-infarto. Follow-up a 4 anni.

We performed a prospective study to evaluate the prognostic significance and the natural history of late ventricular potentials (LPs) in 209 patients (165 males and 44 females; mean age 59.8 +/- 10 years) who survived acute myocardial infarction. Signal-averaged electrocardiograms (SA-ECGs) were performed before hospital discharge (16 +/- 5 days) and after four years (mean follow-up 42 +/- 7 months). SA-ECGs were processed using a 40 Hz high-pass bidirectional filter. Duration of "filtered" QRS (normal value < 120 msec), duration of the low-amplitude signals (n.v. < 39 msec) and last 40 msec voltage of the QRS complex (n.v. > 20 microV) were measured. LPs were defined as the presence of two or more abnormal values. In addition, 24-hour Holter monitoring was performed in all patients, and left ventricular ejection fraction (LVEF) was determined by scintigraphy in 120 (57.4%). Sixty patients (28.7%) had LPs before hospital discharge (group 1), and 149 (71.3%) had normal SA-ECGs (group 2). During the follow-up period there were 10 arrhythmic events, 7 of which were sudden deaths, and three cases of sustained ventricular tachycardia. SA-ECG was repeated in 141 patients (68%). The mean values of SA-ECG's parameters did not change significantly between the two controls, and the correlation was good for all of them. Despite this, spontaneous normalization of SA-ECGs occurred in 21 patients (60%) and the subsequent appearance of LPs was seen in 13 (12%); in these latter, the SA-ECG's parameters measured before hospital discharge were "borderline" and significantly different from those who did not change. The sensitivity of SA-ECG as a predictor of arrhythmic events was 80% and the specificity 74%. Patients with arrhythmic events had a longer filtered QRS (126 +/- 33 vs 103 +/- 12 msec; p < 0.001), longer duration of the low-amplitude signals (57 +/- 23 vs 32 +/- 11 msec; p < 0.001), lower voltages (17 +/- 8 vs 36 +/- 24 microV; p < 0.001), and, moreover, higher peak CK values, lower LVEF and higher value of Lown modified class. In conclusion, SA-ECG confirms its value in identifying patients at risk of arrhythmic events after myocardial infarction. SA-ECG recordings taken before the discharge can be used to predict serial changes during follow-up.

Clinical correlation between diabetic and non diabetic patients with myocardial infarction.

We have studied 130 patients with diabetes mellitus and 455 patients without. All the patients were consecutively admitted to our Coronary Care Unit with their first myocardial infarction. We have observed a higher incidence of heart failure, in-hospital mortality, atrial fibrillation, conduction abnormalities, and post-infarction angina among diabetics. Nevertheless, diabetic patients do not show evidence of larger infarcts than those without diabetes. In our patients the higher mortality among diabetics is related to an increased occurrence of left ventricular failure. Moreover, post-infarction ischemic episodes are more common compared with non diabetics. Since infarcts in diabetics do not seem to be more extensive than in non diabetics, we suggest, in accordance with others, that the poorer outcome among diabetic patients with AMI could be related to an underlying cardiac dysfunction of diabetics in addition to coronary artery diseases.

Ventricular and supraventricular arrhythmias in clinically silent right ventricular infarction.

To study the relationship between clinically silent right ventricular infarction and the incidence of a-v block, atrial and ventricular arrhythmias, 100 patients with inferior wall myocardial infarction underwent equilibrium gated radioisotopic angiocardiography. Fifty-four of them had radioisotopic evidence of right ventricular involvement and 43 (80%) of them had a-v block and/or supraventricular arrhythmias during the acute phase of the infarct, while only 10 (22%) of the 46 patients without right ventricular involvement did. As regards the incidence of ventricular tachyarrhythmias, 14 (26%) patients with right ventricular involvement had ventricular tachycardia and/or fibrillation, while only one patient without right ventricular involvement had ventricular tachycardia, and no patients had ventricular fibrillation. Moreover, V4R-precordial lead showed a sensitivity in predicting the risk of developing a-v block/supraventricular arrhythmias and ventricular tachyarrhythmias of 0.84 and 0.79, respectively. Therefore, right ventricular involvement should be suspected when atrial arrhythmias, a-v block and ventricular tachyarrhythmias are found in early acute inferior wall myocardial infarction. On the other hand, when right precordial lead V4R in early acute inferior infarction shows ST-elevation and/or a QS pattern, the sudden occurrence of these arrhythmias should be suspected, and possibly prevented.