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Biomedical subjects

A Iacono

Publications and source records attributed to A Iacono.

At least 55 records · Page 3Linked to original sources

Clinical significance of CMV-specific T helper responses in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) disease continues to be a major problem for lung transplant patients who generate an inefficient immune response to control this viral infection. Both T helper and cytotoxic T cells are thought to play an important role in prevention and control of CMV disease. We investigated the clinical significance of CMV-specific memory responses in lung transplant recipients. METHOD: Peripheral blood samples (140) were collected from 99 lung transplant recipients. Patients were grouped according to their pre-transplant CMV serological status as recipient/donor (R-/D+, 25 patients), 28 R+/D+ patients, 35 R+/D- patients and 11 R-/D- patients. Memory responses to CMV whole antigen, 5 CMV proteins, and tetanus toxoid (TT) were measured in a 6-day proliferative assay. Results were expressed as the stimulation index (SI = experimental cpm/background cpm), and were considered positive if the SI was >3 and the cpm values were over 1,000. RESULTS: The frequency of positive CMV memory responses was similar in three groups: 64% for R-/D+, 63% for R+/D+ and 56% for R+/D- except for R-/D- (21%). The memory response to TT was similar for all four groups (70% of samples were positive). The level of responsiveness to individual CMV proteins was much higher in R+/D+ group (65%) than the other two groups (35% for R+/D-, and 31% for R-/D+). We determined the temporal relationship between the presence of CMV-specific memory responses and the diagnosis of CMV disease. In the R-/D+ group, 16 of 17 patients who had CMV disease eventually developed CMV-specific memory. In those patients (n = 3) who failed to develop CMV-specific T helper response for a prolonged time, all had recurrent CMV disease. In the R+/D+ group, 4 of 8 patients with CMV disease exhibited CMV-specific memory responses. Three of 4 patients in whom we observed a persistent absence of CMV-specific memory had multiple episodes of CMV pneumonitis. In the R+/D- group, only one of 4 patients with CMV disease had suppressed CMV-specific memory response after first episode of CMV pneumonitis and had recurrent disease. CONCLUSION: In lung transplant recipients, the loss or persistent lack of CMV-specific memory following infection was associated with chronic CMV disease. These data suggest that monitoring T helper memory responses following primary CMV infection or after augmented immunosuppression for treatment of rejection may identify those patients at risk for morbidity associated with recurrent CMV disease.

Antigens, Viral↗

Effects of losartan on hypertension and left ventricular mass: a long-term study.

This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients, mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients, mean age 56+/-7 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group: 11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients

Adult↗

Arrhythmias in patients with mechanical ventricular dysfunction and myocardial stretch: role of mechano-electric feedback.

Patients with dilated cardiomyopathy, ventricular volume or pressure overload, or dysynergistic ventricular contraction and relaxation are prone to develop severe ventricular arrhythmias. In these patients it has been suggested that the abnormal mechanics of contraction can disturb 'mechano-electric feedback', also known as 'contraction-excitation feedback', which is defined as the development of electrophysiological changes during or after changes in mechanical loading. This electrical instability, expressed by significant changes in ventricular repolarization and refractoriness and by the development of afterdepolarizations, has been variously reported in isolated tissues and isolated ventricles as well as in hearts in vivo. Furthermore, it is known that many patients with supraventricular tachycardia but otherwise structurally normal hearts can develop atrial fibrillation and that atrial arrhythmias frequently occur in the setting of acute or chronic increases in atrial size and pressure. It is possible that changes in atrial load directly alter the electrophysiological properties of the atrium by an analogue mechanism of contraction-excitation feedback. This paper reviews the literature concerning mechanoelectric feedback involvement in rhythm disorders, with the aim of investigating, through basic and clinical research, the clinical and therapeutic implications.

Arrhythmogenic Right Ventricular Dysplasia↗

[The effectiveness and tolerability of losartan and effect on left ventricular mass in patients with essential hypertension].

The purpose of our study was to evaluate the antihypertensive efficacy, tolerability and effects on left ventricular mass of losartan over 10 months in patients with essential hypertension. Losartan is a selective angiotensin II receptor-antagonist. The whole study comprised 89 hypertensive patients who were randomized, at baseline, to 10 months of double-blind once daily treatment with losartan 50 mg (L Group, n = 49, mean age 55 +/- 13 years) or hydrochlorothiazide 25 mg (HCTZ Group, n = 40, mean age 56 +/- 10 years). Routine hematology, blood chemistry and urinalysis were performed before and after 5 and 10 months; standard electrocardiography, ambulatory non invasive 24-hours blood pressure monitoring, M-mode echocardiography, psychometric test and quality of life evaluation were obtained from all the patients before and after 10 months. In patients non responding after 4 weeks, hydrochlorothiazide 25 mg or losartan 50 mg was added in the L Group and in the HCTZ Group, respectively (L-HCTZ Group). The results showed good tolerability and a significant mean systolic and diastolic blood pressure reduction in all groups (L Group from 157/96 +/- 9/7 to 137/85 +/- 9/5 mmHg, p < 0.001; HCTZ Group from 158/97 +/- 11/8 to 150/91 +/- 9/7 mmHg, p < 0.003; L-HCTZ Group from 159/98 +/- 9/5 to 141/88 +/- 6/4 mmHg, p < 0.001), although L and L-HCTZ treatment were more effective during 24 hours than HCTZ. Moreover, a remarkable reduction in left ventricular mass index was obtained after 10 months only in the L Group (from 138.4 +/- 26.2 to 127.2 +/- 23.1 g/m2, p < 0.04) and in the L-HCTZ Group (from 140 +/- 20.3 to 125.5 +/- 20.1 g/m2, p = 0.126). Finally, in patients treated with losartan the results of psychometric test significantly improved (L Group: p < 0.05; L-HCTZ Group: p < 0.05) and a positive remarkable change in the quality of life was observed (L Group: p < 0.05; L-HCTZ Group: p = 0.083). In conclusion, losartan in monotherapy or in association with hydrochlorothiazide, was well tolerated, respected the quality of life, and produced a significant and remarkable reduction in blood pressure and left ventricular mass in hypertensive patients.

Adult↗

[Dispersion of ventricular recovery time following surgery for tetralogy of Fallot: correlation with negative prognostic factors].

Malignant ventricular arrhythmias have been reported in patients with repaired tetralogy of Fallot. The aim of this study was to examine ventricular repolarization time indexes, in terms of both absolute measures and dispersion across the myocardium, in young patients operated on for tetralogy of Fallot (32 patients; 19 males and 13 females, mean age 11.1 +/- 3.4 years); these electrocardiographic parameters have been shown to be effective in the identification of electrical myocardial instability and hence of risk for ventricular arrhythmias too. The electrocardiographic data of the study group were compared with those of 22 age-matched asymptomatic control subjects (14 males and 8 females, mean age 12 +/- 1.5 years). Furthermore it has also been investigated the possible influence on ventricular repolarization of known negative prognostic factors relative to the surgical approach, age at intervention, and presence of pulmonary obstruction and/or regurgitation. No patients in the study group revealed at the Holter recordings and/or at the exercise test severe ventricular arrhythmias. From the analysis of ventricular depolarization, expressed by QRS duration, emerged that it resulted significantly longer in total Fallot group (p < 0.0001), and in each subgroup (p < 0.05) compared to the control group. Particularly, patients operated through a right ventricular approach showed higher values of QRS interval (p < 0.05) than those operated through combined transatrial-transpulmonary approach. All patients operated on for tetralogy of Fallot showed, compared to control subjects, a non homogeneous prolongation of ventricular repolarization across the myocardium, as confirmed by the significant increase in the absolute indexes of ventricular repolarization, JTc (p < 0.001), QT (p < 0.0001) and QTc (p < 0.0001) with a concomitant prolongation of the indexes of dispersion of ventricular recovery time, QTc dispersion (p < 0.0001), JTc dispersion (p < 0.0001), "adjusted" QTc dispersion (p < 0.05) and T peak-T end interval (p < 0.0001). The non homogeneous ventricular repolarization across the myocardium, preceding the development of arrhythmic events, could be the effect of the right ventricular morphological and functional changes of tetralogy of Fallot predisposing to the development of ventricular reentry tachyarrhythmias.

Adolescent↗

[Complex ventricular arrhythmias and carvedilol: efficacy in hemodialyzed uremic patients].

Carvedilol has been shown to be effective in systemic hypertension and coronary artery disease in patients with end-stage renal disease, on maintenance hemodialysis. The aim of our study was to assess the effects of carvedilol on ventricular arrhythmias in these patients. Ninety-eight uremic patients maintained on hemodialysis, with complex ventricular arrhythmias (class III, IV and V of Lown's classification), not only during dialysis, were included in the study. They were divided into two groups, with mild-to-moderate hypertension or coronary artery disease. The efficacy and safety of carvedilol (50 mg/day) was compared to placebo in a 6-week randomized, double-blind study. Carvedilol significantly reduced, in both hypertensive and ischemic patients, total ventricular premature contractions (82.7 +/- 11.3 vs 358.1 +/- 73.9, p < 0.001; 88.3 +/- 24.4 vs 369.9 +/- 77.8, p < 0.001), repetitive ventricular premature contractions (1.3 +/- 1.3 vs 6.3 +/- 3.5, p < 0.001; 1.2 +/- 0.7 vs 6.9 +/- 2.6, p < 0.001) and episodes of ventricular tachycardia (1.1 +/- 1.2 vs 11.8 +/- 7.5, p < 0.001; 1.4 +/- 1.2 vs 14.0 +/- 8.3, p < 0.001). In placebo-treated patients, instead, these parameters were not significantly changed (329.1 +/- 76.5 vs 361.7 +/- 71.7, NS, and 324.6 +/- 79.7 vs 359.3 +/- 58.1, NS; 6.2 +/- 3.7 vs 7.3 +/- 3.7, NS, and 4.9 +/- 2.2 vs 6.1 +/- 3.2, NS; 9.8 +/- 6.3 vs 13.3 +/- 8.0, NS, and 9.0 +/- 6.2 vs 12.4 +/- 7.8, NS). Carvedilol confirmed a significant effect on myocardial ischemia and systemic hypertension. No significant side effects were reported. Ventricular arrhythmias are frequent in patients with end-stage renal disease maintained on hemodialysis. They are often due to an underlying cardiac disease, namely systemic hypertension with left ventricular hypertrophy and coronary artery disease. The results of our study show that the antiarrhythmic effect of carvedilol is linked, at least partly, to an improvement of the underlying cardiac disease. Uremic patients have a chronic increase in adrenergic tone, with a direct correlation between norepinephrine plasmatic concentration and frequence of premature ventricular contractions. Beta-blockers are very important in these patients because of their modulation on the adrenergic system. They also reduce potassium flow, from extracellular to intracellular fluid. Therefore carvedilol can affect the sudden hypokalemia occurring in the first phase of hemodialysis treatment, that may be an important cause of intradialytic arrhythmias.

Aged↗

[New experimental evidence of complex dynamics of heart beat. II. Correlation dimension, Lyapunov's exponents].

In this paper we applied mathematical techniques of non-linear dynamics, to an ECG signal. The first step is to compute the shift-delay time, via average displacement of the digital ECG. Phase space is constructed at a prescribed shift-delay and correlation dimension and dominant Lyapounov exponent versus the embedding dimension are monitored. This technique was applied to 5 healthy volunteers and 4 patients with VVI pacemaker.

Algorithms↗

Atrial fibrillation: what are the effects of drug therapy on the effectiveness and complications of electrical cardioversion?

Atrial fibrillation is the most common cardiac rhythm disorder associated with hospitalization. Two therapeutic options have been available: antiarrhythmic drug therapy, and external or internal electrical cardioversion. Electrical cardioversion of atrial fibrillation remains one of the most widely used and effective treatments for the restoration of normal sinus rhythm. However, many patients continue to receive an antiarrhythmic drug before and after cardioversion in an attempt either to cardiovert the arrhythmia chemically or to maintain sinus rhythm after successful cardioversion. Because some pharmacological agents can affect the cardioversion procedure for atrial fibrillation or flutter, and because many patients with such arrhythmias may require electrical cardioversion when they are taking antiarrhythmic drugs, the question of a possible effect of drug therapy on the efficacy and safety of electrical cardioversion of atrial fibrillation arises. Early reports of direct current cardioversion provoking potentially lethal ventricular arrhythmias raised suspicions of an arrhythmogenic role for digoxin antiarrhythmic therapy, and it is customary to withhold these drugs for 24 to 48 h before cardioversion is attempted. However, this complication is likely to arise only in patients who are close to, or actually manifesting, signs of drug toxicity. On the other hand, treatment with therapeutic concentrations of antiarrhythmic drugs before cardioversion may in some cases be associated with a significant reduction in the number of shocks and decreased energy required to restore sinus rhythm, a lower incidence of postshock arrhythmias and a reduced risk of early recurrence of atrial fibrillation.

Amiodarone↗

[Syndrome X and microvascular angina].

The term X syndrome is used to indicate a group of patients who present anginous symptoms and ischemic-type electrocardiographic alterations which appear during exercise tolerance tests, dipiridamol tests or Holter's dynamic monitoring where coronary ultrasonography reveals no evident coronary lesions, vasospastic angina, arterial hypertension and/or diabetes mellitus, block of the left branch when resting or exercising, cardiomyopathy or valvulopathy. The highest incidence is in females with a mean age of around 50. A reduced reserve of coronary flow, highlighted both in response to vasodilatators or rapid stimulation and by positron emission tomography (PET), underlies this syndrome. It is thought to be caused by a dysfunction of the coronary microcirculation which consists in a deficit of the endothelium-dependent vasodilatory mechanisms, probably also owing to the accumulation of vasoconstrictive type substances, like endothelin-1. In addition to a dysfunction of the coronary microcirculation, one widely backed hypothesis concerns the existence of an altered perception of painful symptoms in patients with X syndrome: the anomalous constriction of prearteries might cause an increased release of adenosine, able to provoke angina despite the scarce signs of myocardial ischemia in terms of the metabolic or functional profile. From a therapeutic point of view, treatment of these patients is often ineffective: treatment should be based on the use of nitrates, calcium-antagonists or beta-blockers, if necessary moving on to other forms of therapy (aceinhibitors, xanthine methylate, estrogens, alphablockers, imipramine); the simultaneous use of tranquillizers may be useful in view of the anxious personality often characteristic of these patients.

Female↗

Repolarization abnormalities in patients with idiopathic ventricular tachycardias.

STUDY POPULATION: Twenty patients without laboratory evidence of cardiac disease who underwent electrophysiological study because of recurrent ventricular tachyarrhythmias. PATIENTS AND METHODS: The study population was divided into two groups: group A (20 patients [six males and 14 females] mean age 42.2 +/- 13 years), with idiopathic ventricular tachycardia (VT), and group B (30 controls [10 males and 20 females] mean age 43.6 +/- 16 years). Noninvasive multiparametric analysis of the ventricular repolarization phase was performed on the standard 12-lead electrocardiogram by using a digitizer connected with a computerized system. The intervals JT, heart rate-corrected JT (JTc), JT apex (JTa), heart rate-corrected JTa (JTac), T apex T end (TaTe) and heart rate-corrected TaTe (TaTec) were measured and considered to be representative of the whole depolarization process. QT dispersions (QTeD) and QTc dispersions (QTecD) were calculated to assess the degree of spatial inhomogeneity of action potential duration. RESULTS: Patients in group A had higher JT (272 +/- 36 ms versus 265 +/- 25 ms, P = 0.01), JTc (336 +/- 28 ms versus 318 +/- 18 ms, P = 0.01), JTa (210 +/- 28 ms versus 185 +/- 28 ms, P = 0.001) and JTac (240 +/- 20 ms versus 215 +/- 13 ms, P < 0.001) values than those of patients in group B, despite shorter TaTe (71 +/- 10 ms versus 90 +/- 18 ms, P < 0.001) and TaTec (88 +/- 12 ms versus 110 +/- 12 ms, P < 0.001). Moreover, QTeD and QTecD were significantly longer in group A than in group B (55 +/- 18 ms versus 42 +/- 19 ms [P = 0.01] and 80 +/- 18 ms versus 55 +/- 28 ms [P = 0.001], respectively). CONCLUSIONS: Patients with idiopathic VT exhibit inhomogeneous prolongation of ventricular repolarization, due to a considerable increase in the initial part in association with a shorter terminal phase, as well as a greater dispersion of ventricular repolarization.

Adult↗

[Incremental doses of diltiazem in patients with coronary artery disease in end-stage renal failure maintained on hemodialysis: which is the optimal dose?].

End-stage renal disease patients on maintenance hemodialysis suffering from coronary artery disease probably receive too low doses of calcium-antagonists, because the attempt to avoid adverse effects prevails the well-documented antianginal activity of the drug. The aim of our study was to assess the safety and efficacy of incremental doses of diltiazem in treating angina pectoris in hemodialyzed patients with coronary artery disease, to identify the optimal dose. Ninety-four chronic hemodialyzed patients (59 males and 35 females; mean age 55.2 +/- 3.3 years; on periodic dialysis for 80.3 +/- 25.6 months) with coronary artery disease and more than 5 min of transient myocardial ischemia during 48 hours of Holter monitoring were included in the study. A double-blind, randomized, placebo-controlled trial design was used. Incremental doses of diltiazem (from 120 to 240 mg/day) were administered in 4 months. At doses of 120 and 180 mg/day it was observed a statistically significant reduction in the number and duration of total and symptomatic ischemic episodes in 48 hours, compared with baseline (p < 0.001). Instead, the number and the duration of silent ischemic episodes did not significantly change (NS). The efficacy on silent myocardial ischemia was obtained only with the dosage of 240 mg/day (p < 0.001). If this dosage was obtained with a sustained-release formulation (120 mg twice a day), the efficacy was similar to the administration of 4 tablets/day of 60 mg, but the tolerability was better, especially during dialysis. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours, one from 6.00 to 9.00 a.m. and another from 4.00 to 8.00 p.m., just during the dialysis. Both peaks were reduced only with 240 mg/day. In conclusion, this study demonstrates that sustained-release diltiazem (120 mg twice a day) is greatly useful in patients with coronary artery disease on maintenance dialysis because it reduces the frequency of silent ischemic episodes, has a good tolerability, and modifies the circadian pattern of ischemic episodes, reducing both peaks during the day.

Calcium Channel Blockers↗

Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine.

BACKGROUND: The purpose of this study was to correlate cytokine gene expression from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) with graft histology in recipients with persistent acute rejection treated with aerosolized cyclosporine (ACsA). METHODS: We measured mRNA for interleukin (IL) 6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13), (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and (3) with "refractory" acute rejection that failed to respond to conventional immunosuppression (n=17). In the latter group, ACsA was initiated. RESULTS: BAL cell IL-6 and IFN-gamma were highest in recipients with refractory rejection compared with recipients with steroid-responsive rejection and recipients with no rejection. Improvement in rejection histology occurred in 15 of 17 recipients who were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs. after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32 vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02, respectively). CONCLUSIONS: IL-6 and IFN-gamma mRNA expression from BAL cells was highest in those recipients with refractory histologic acute rejection. ACsA was associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and PBL.

Acute Disease↗

Autonomic nervous system imbalance and left ventricular systolic dysfunction as potential candidates for arrhythmogenesis in Becker muscular dystrophy.

We evaluated the arrhythmic profile in a population of 20 Becker muscular dystrophy (BMD) patients searching for possible correlations between the severity of the arrhythmic events, the cardiac autonomic balance (assessed by heart rate variability analysis in the time domain) and the degree of left ventricular systolic impairment. A population of 14 male healthy individuals served as the control group. BMD subjects exhibited lower values of SDNN (P=0.013), SDANN index (P=0.008) and 24-h mean heart rate (P=0.002). The total number of premature ventricular beats (totPVB) and the number of PVB out of 1000 heartbeats (PVB/1000) appeared also higher in BMD subjects (P=0.05 and P=0.046, respectively). No difference was found in terms of 24-h mean QTc and 24-h longest QT among the two groups. TotPVB and PVB/1000 were inversely related to both the ejection fraction (r= -0.620, P=0.004 and r= -0.517, P=0.019) and to the shortening fraction (r= -0.568, P=0.009 and r= -0.469, P=0.037). Twenty-four-h mean QTc was also inversely related to both the ejection fraction (r= -0.520, P=0.019) and the fractional shortening (r= -0.491, P=0.028). These data suggest that in BMD there is cardiac autonomic imbalance characterized by sympathetic predominance and an increased susceptibility to ventricular arrhythmias, even in the absence of overt cardiomyopathy. Furthermore, the severity of the arrhythmic profile in BMD appears closely related to the degree of left ventricular systolic dysfunction.

Adult↗

QTc and not QTc dispersion behavior affects the occurrence of ventricular extrasystole during exercise in infarcted patients.

Both a long QTc and a large QTc dispersion (QTcd) can predispose infarcted patients to ventricular arrhythmias. The former simply reflects a general prolongation of ventricular recovery time, whereas QTcd is useful for revealing regional inhomogeneities of ventricular repolarization. The aim of our study was to evaluate QTc and QTcd behavior during exercise in 50 patients (all men) with previous myocardial infarction, and its possible correlation with the occurrence of exercise-induced premature ventricular complexes (EIPVC). Our patients underwent ergometric stress test with a load increase of 25 W, every 2 min, until the maximal age-related heart rate or symptoms were obtained, followed by a 10-min recovery phase. QTc and QTcd measurement was performed at rest (BS) and during exercise at two progressively increasing heart rate steps: 100-115 beats/min (T1) and 116-130 beats/ min (T2). The patients were divided into two groups according to the absence (group A; n = 22) or presence (group B; n = 28) of EIPVC. In terms of QTcd, no significant difference was found between the two groups at BS, T1, and T2. As for the mean QTc (QTcm), it was significantly longer in group B at BS (416 +/- 22 ms versus 395 +/- 19 ms; P = 0.001) and at T1 (431 +/- 24 ms versus 410 +/- 8 ms; P = 0.0001). When group B was further differentiated into two subgroups-Bx and Bz-according to the severity of EIPVC, we noted that patients with the most severe arrhythmic response (group Bz; n = 12) showed a persisting, significantly longer QTcm than group A (BS, 426 +/- 28 ms versus 395 +/- 19 ms; P < 0.05; T1, 445 +/- 24 ms versus 410 +/- 8 ms; P < 0.05; T2, 427 +/- 17 ms versus 412 +/- 14 ms; P < 0.05), and group Bx (n = 16) (BS, 426 +/- 28 ms versus 409 +/- 15 ms; P < 0.05; T1, 445 +/- 24 ms versus 420 +/- 19 ms; P < 0.05; T2, 427 +/- 17 ms versus 410 +/- 17 ms; P < 0.05). Group Bx showed a significantly longer QTcm than group A only at BS (409 +/- 15 ms versus 395 +/- 19 ms; P < 0.05). No significant difference in QTcd was found between the three groups at BS, T1, and T2. We also noted that the relationship between QTcm and QTcd was modified by the exercise, changing from a trend of direct relation at BS, towards an inverse one during effort, which reached significance at T2 (r = -0.319; P = 0.037). Based on our data, EIPVC occurrence seems to be more affected by the total duration rather than by regional inhomogeneities of the ventricular recovery time. In those patients with the most severe arrhythmic response, the autonomic modifications generated by the exercise succeed in attenuating only the regional inhomogeneities, but do not eliminate the differences in total duration of the repolarization period.

Aged↗

Ventricular repolarization time indexes following anthracycline treatment.

The anthracyclines, doxorubicin and daunorubicin, are antibiotics effective in the treatment of many malignancies. However, their usefulness is limited by the development of potentially fatal cardiotoxicity. Cardiac monitoring by a noninvasive test capable of identifying patients at high risk of cardiac damage, before the ejection fraction deteriorates would have clinical utility. Electrocardiograms and echocardiograms are routinely utilized for noninvasive assessment of myocardial function. However, of the ECG abnormalities described, none has been noted to be of consistent predictive value for cardiotoxicity. The aim of this study was to assess the effects of doxorubicin on ventricular repolarization time indexes, as they have been shown to be effective in the identification of electrical myocardial instability and, hence, in the identification of risk for either arrhythmia or heart failure. For this reason, electrocardiograms were compared in 35 cancer patients at the first presentation (drug-free state) and after 29.4 +/- 37.65 weeks of treatment with doxorubicin. The results of the present study showed that after only a short period of treatment with doxorubicin there was a significant increase in ventricular recovery time dispersion indexes (QTc, JT, and JTc dispersion, and their "adjusted" values). Thus, increased regional variation in ventricular repolarization could be, in the absence of a significant modification of the echocardiographic parameters, an early marker of an electropathy, due to the early cardiotoxic action of doxorubicin on myocardial cells, eventually leading to heart failure.

Adult↗

Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients.

Lung transplant recipients who have persistent acute cellular rejection are at increased risk for the development of chronic rejection, the leading cause of reduced long-term survival. This study evaluated the use of aerosolized cyclosporine as rescue therapy for unremitting acute rejection. Between June 1993 and March 1996, 18 patients with rejection that failed to resolve after therapy with pulse steroids and antilymphocyte globulin were enrolled in the study. Aerosolized cyclosporine A (300 mg) treatment was initiated for 10 consecutive days followed by a maintenance regimen of 3 days per week. Efficacy was assessed by graft histologic and pulmonary function testing. With the use of linear regression, results in these patients were compared with those in 23 control patients, matched for histologic acute rejection, who had continued to receive conventional rescue therapy. Two patients were unable to tolerate the treatments and were withdrawn from the study. Significant improvement in histologic rejection occurred in 14 of the remaining 16 patients after a mean of 37 days of aerosolized cyclosporine therapy. Measures of forced vital capacity and forced expiratory volume in 1 second (change in percent predicted/100 days plus or minus the standard error) increased over time in the treated patients whereas the condition of control patients declined despite repeated attempts at conventional rescue (forced vital capacity, aerosolized cyclosporine group, 4.6 +/- 2.9 vs control group -8.1 +/- 1.9, p = 0.001; forced expiratory volume in 1 second, aerosolized cyclosporine group, 2.1 +/- 4.4 vs control group -9.8 +/- 2.6, p = 0.043). Renal and hepatic toxicity during cyclosporine therapy was not observed. The incidence of acute histologic rejection (> or = A2) decreased from 2.49 +/- 0.68 episodes/100 days before aerosolized cyclosporine therapy to 0.72 +/- 0.3 episodes/100 days (p < 0.05). In summary, aerosolized cyclosporine is a safe and effective therapy for acute rejection that has failed to improve with conventional treatment.

Acute Disease↗