Psychological status and role of caregivers in the neuro-rehabilitation of patients with severe Acquired Brain Injury (ABI).

OBJECTIVE: To investigate the relationships between (a) the psychological status of the caregiver, (b) the specific features of caregiving as perceived by the cognitive therapist in neuro-rehabilitation, (c) the caregivers' subjective approach to neuro-rehabilitation, and (d) the functional outcome of the patient. METHODS: Twenty-four patients with severe acquired brain injury and their 24 caregivers participated in this observational study. Caregivers underwent a psychological assessment examining emotional distress, burden and family strain; their subjective approach to neuro-rehabilitation has been evaluated by two specific answers. The patients' cognitive therapists responded to an ad-hoc questionnaire, namely the "Caregiving Impact on Neuro-Rehabilitation Scale" (CINRS), evaluating the features (i.e., amount and quality) of caregiving. Finally, the functional outcome of the patient was assessed through standardized scales of disability and cognitive functioning. RESULTS: The caregivers' psychological well-being was associated to the features of caregiving, to the subjective approach to neuro-rehabilitation, and to the functional recovery of their loved ones. A better caregivers' approach to neuro-rehabilitation was also associated to an overall positive impact of caregiving in neuro-rehabilitation and to a better functional outcome of the patients. CONCLUSIONS: We posited a virtuous circle involving caregivers within the neuro-rehabilitation process, according to which the caregivers' psychological well-being could be strictly associated to a better level of caregiving and to a better functional outcome of the patients that, in turn, could positively influence the caregivers' psychological well-being. Although preliminary, these results suggest a specific psycho-educational intervention, aimed at improving the caregivers' psychological well-being and at facilitating their caring of the loved one.

Regression of hypertensive myocardial hypertrophy does not affect ultrasonic myocardial reflectivity: a tissue characterization study.

OBJECTIVE: Ultrasonic backscatter from the myocardial walls is directly related to the morphometrically or biochemically evaluated collagen content in man, and shows a normal pattern of quantitatively assessed ultrasonic backscatter in hypertensive patients, even in the presence of left ventricular hypertrophy. Whether the pharmacologically induced regression of left ventricular hypertrophy in hypertensive patients is accompanied by a disproportionate increase in relative connective tissue content is not yet known. The objective of the present study was to assess the effects of regression of left ventricular hypertrophy on the quantitatively evaluated myocardial reflectivity in essential hypertensives. DESIGN: We evaluated 19 mild-to-moderate essential hypertensives with echocardiographically assessed left ventricular hypertrophy, before and after 8 months' effective antihypertensive therapy with 20-40 mg enalapril once a day, associated with diuretics or calcium antagonists, or both, in six patients to achieve optimal blood pressure control. Using a modified echo machine developed in the Institute of Clinical Physiology, Pisa, an on-line radio-frequency analysis was performed to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall. The integrated values of the radio-frequency signal from the myocardial walls were normalized for those from the pericardial interface and were expressed as percentages (integrated backscatter index). RESULTS: In comparison with baseline, the treated hypertensives showed significant decreases in mean blood pressure, left ventricular mass index, and septal and posterior wall thickness. However, integrated backscatter index values were similar at baseline and after therapy for both the septum and the posterior wall. CONCLUSION: Antihypertensive therapy with enalapril does not increase myocardial reflectivity, although it does induce regression of left ventricular hypertrophy. This suggests that, in accord with experimental data, regression of hypertrophy is achieved by enalapril through a proportionate regression of the myocyte and connective tissue components of the myocardium.

[Neurohormonal mechanisms in cardiac insufficiency. Possible therapeutic implications]. / Meccanismi neurormonali nell'insufficienza cardiaca. Possibili implicazioni terapeutiche.

Neurohormonal mechanisms play an important role in pathogenesis of left ventricular dysfunction. Analysis of traditional therapeutic strategies for heart failure used in the past is disappointing. Recent therapeutic strategy that aims to treat earlier patients with ventricular dysfunction with agents that counteract neurohormonal activation, seems to be more effective. However conventional drugs such as vasodilator agents, digitalis and diuretics are still useful for treatment of overt heart failure, due to their proven hemodynamic benefits. A lot of current clinical trials, in the future, can help us to solve this problem. In this issue evolving concepts of pathophysiology of chronic heart failure and how these pathophysiologic concepts lead to the rational treatment are discussed.

Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study.

Ultrasonic backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. The integrated backscatter is also increased in hypertrophic cardiomyopathy, whereas it gives normal values in the physiological hypertrophy of elite athletes. We assessed the quantitatively evaluated myocardial reflectivity in 46 mild to moderate, clinically uncomplicated essential hypertensive patients, with echocardiographically assessed normal regional and global left ventricular function, and 22 age- and sex-matched normotensive control subjects. With an echo prototype implemented in our institute, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal of myocardial walls were normalized for those of the pericardial interface and expressed as a percent (integrated backscatter index). Hypertensive patients and control subjects differed in mean blood pressure (119 +/- 11 versus 95 +/- 5 mm Hg, p < 0.001) and left ventricular mass index (134 +/- 31 versus 105 +/- 21 g/m2, p < 0.001). However, integrated backscatter index overlapped for both the septum (28 +/- 17% versus 25 +/- 6%, p = NS) and the posterior wall (13 +/- 7% versus 13 +/- 4%, p = NS). In the hypertensive group, there was no detectable correlation between septal integrated backscatter index and either septal thickness (r = -0.26, p = NS) or mean arterial pressure (r = -0.14, p = NS). Hypertensive patients showed a normal pattern of quantitatively assessed ultrasonic backscatter, even in the presence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ventricular hyperkinetic arrhythmias: a current therapeutic problem. The possible greater use of beta blockers]. / Le aritmie ipercinetiche ventricolari: problema terapeutico attuale. Possibile maggiore impiego per i betabloccanti.

The therapeutic approach to cardiac arrhythmias is constantly evolving due to our improved understanding of their mechanisms and clinico-prognostic implications, even if uncertainties and controversies continue to be a marked feature of this sector, perhaps more than in any other field of medicine. The frequent finding of cardiac arrhythmias in the healthy and cardiopathic population justifies the importance which the question of the diagnosis and treatment of cardiac rhythm disorders has now assumed, even if, as far as the latter is concerned, the aggressive approach has been considerably modified over the past years. This has occurred in view of the still unproven value of indiscriminate anti-arrhythmic treatment for the purposes of prolonging life. This treatment has only been demonstrated to be of value in a few studies in selected subgroups of high-risk patients. In addition, it should be underlined that it has been reported that anti-arrhythmic drugs may possible aggravate or induce new arrhythmia. This potential pro-arrhythmic effect has become increasingly recurrent due to the widespread use and diffusion of this category of drugs. Such considerations should therefore encourage greater caution in the use of these drugs. Cardiac arrhythmias may be benign or life-threatening, symptomatic or asymptomatic; they may be a warning sign of sudden death, or be the cause or effect of heart failure, be the expression of an acute or chronic heart disease, or the clinical manifestation, at a cardiac level, of an extracardiac pathology. Within this broad-ranging clinical context, arrhythmia often gives rise to therapeutic dilemmas which must be resolved with extreme rationality, taking into account the results of all available clinical trials. The results of the Cardiac Arrhythmias Suppression Trial (CAST) showed that clinical judgements of therapeutic efficacy, made in the absence of carefully controlled studies, are often incorrect. On the basis of these findings beta-blocking drugs may find increasing use, since while they are not anti-arrhythmic drugs in the strict sense of the term, they are safer due to their negligible pro-arrhythmic effect, the lower incidence of collateral effects and their proven efficacy in post-infarction. The role of beta-blockers in the treatment of manifest heart failure should not be over-looked, since by countering the deleterious effect of increased catecholamines they may improve the prognosis, thus reducing the incidence of sudden death.

Gallopamil and diltiazem: a double-blind, randomized, cross-over trial in effort ischaemia.

The aim of this study was to evaluate the efficacy and possibly the mechanism of action of gallopamil and diltiazem in a double-blind crossover trial in patients with effort ischaemia. Twenty male patients (mean age 57 +/- 6 years) with documented coronary atherosclerosis and exercise-induced ischaemia (ST depression greater than or equal to 0.15 mV) completed the study, which consisted of four 7 day periods. At the end of each period a multistage bicycle exercise stress test was performed under placebo (first and third periods) and randomly under gallopamil (50 mg t.i.d.) or diltiazem (90 mg t.i.d.) in the second and fourth periods. Both drugs significantly increased time to ischaemia (0.15 mV ST depression) as compared to placebo, from 7.9 +/- 1.7 min to 8.9 +/- 1.1 min (diltiazem) and 9.1 +/- 1.6 min (gallopamil) with no significant difference between the two drugs, and reduced the maximal extent of ST shift from 0.18 +/- 0.08 mV to 0.13 +/- 0.04 mV (diltiazem) and 0.12 +/- 0.05 mV (gallopamil). Analysis of the results from the whole population showed that the beneficial effect did not appear to be related to any specific parameter. Individual analysis showed that 13/20 patients under gallopamil and 13/20 under diltiazem increased time to ischaemia, while this was unchanged or reduced in the remainder. A positive correlation between changes in time to ischaemia and changes in rate x pressure product at ischaemia was found in both those administered gallopamil (R 0.80, P less than 0.01) and diltiazem (R 0.65, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[The effects of pharmacological treatment in asymptomatic left ventricular dysfunction]. / Effetti del trattamento farmacologico nella disfunzione ventricolare sinistra asintomatica.

It is clearly settled that the management of overt heart failure offers poor prognostic impact due to the advanced setting of the disease. Relief of symptoms, objective benefits, as testified by short-term hemodynamic improvements, are as a matter of fact not reliable prognostic markers. Myocardial dysfunction starts early in the natural history of many cardiac diseases, and runs through the steps of progressive wall remodeling, witnessed by quantitative and qualitative changes in cells, interstitium and connective tissue. Experimental studies offered keys to interventions modulated to oppose the pathophysiological changes present in early myocardial dysfunction. At present, medical therapy has made great strides in testing early myocardial dysfunction. Angiotensin-converting enzyme inhibitors, which retard ventricular dilatation and thus may lower myocardial oxygen consumption requirements seem to offer a unique prognostic profile. Preliminary pilot studies on them and some of many large-scale multicentre trials still in progress reached evidence that this class of drugs is by this time a cornerstone of medical therapy, useful to lower cardiac events-rate in patients with heart failure.

Should we treat silent myocardial ischaemia?

Silent myocardial ischaemia has been documented in various clinical entities. Exercise testing and ambulatory ECG monitoring are the most widely used tests for documenting silent ischaemia, and both exercise-induced and daily life ischaemia have the potential to trigger prolonged functional and structural changes. Numerous clinical investigations in apparently healthy subjects, in stable and unstable angina, in patients with a previous myocardial infarction indicate that ischaemia has an adverse prognostic influence, independent of whether the ischaemia is silent or symptomatic. Methods for documenting silent ischaemia lead to different considerations according to each clinical syndrome of coronary artery disease. This review deals with the different intervention strategies derived from the unique prognostic profiles offered by silent ischaemia in a variety of clinical entities.

[Arterial hypertension and cardiovascular risk. Epidemiological studies, trials and therapeutic implications]. / Ipertensione arteriosa e rischio cardiovascolare. Gli studi epidemiologici, i trial e le implicazioni terapeutiche.

From the analysis of the epidemiological observational studies, among which one of the most famous is the Framingham study that has lasted for more than 30 years, it is evident that the risk of cardiac events and strokes is closely related to the levels of arterial systolic and diastolic blood pressure. Nevertheless, the link between hypertension and cardiovascular risk has very often been discussed, due to the results of therapeutic intervention trials, which have proved satisfactory for cardiovascular risk reduction but disappointing results for coronary disease reduction risk. Possible explanations for these poor results of antihypertensive therapy on coronary disease are different and very numerous. According to many Authors, the blood pressure was not reduced to the programmed levels in all trials and the drug used (diuretics, beta-blockers) possibly had negative effects on the lipid profile. Therefore, waiting data for new trials, will perhaps produce better results in the future taking into consideration all risks of our patient, monitoring a rigorous and steady blood pressure reduction and selecting drugs like calcium-channel blockers and ACE-inhibitors which contain characteristics similar to those ideal for the modern antihypertensive agent.

Thrombolysis in refractory unstable angina.

Multiple drug therapy, including nitrates, beta blockers, calcium antagonists, aspirin, and heparin, has been advocated as effective in the treatment of unstable angina, a syndrome with a multifactorial pathogenesis. Recently, plaque rupture and thrombosis have been demonstrated as the most important pathogenetic mechanisms. Nevertheless, clear-cut results on the effects of thrombolytic treatment in unstable angina are still lacking. Some possible explanations why the medical treatment of unstable angina has still not yet been standardized, whereas that of myocardial infarction has, are suggested. A review of randomized and nonrandomized studies published on this topic evaluating the role of different thrombolytic agents in unstable angina is presented. In addition the role of coronary angiography is discussed. In view of the disappointing results of coronary artery bypass surgery performed in the acute phase of the disease, one of the goals of clinical research is to identify subsets of patients at high and low risk and who undergo different types of therapeutic interventions. To support published data suggesting that total myocardial ischemia has a significant impact on prognosis, we present our results of a study carried out on patients with refractory unstable angina treated with thrombolytic therapy and evaluated with continuous electrocardiographic monitoring in the attempt to correlate total myocardial ischemia with short-term prognosis. Data in favor of the prognostic role of continuous electrocardiographic monitoring in unstable angina are also reviewed. Finally, we propose some suggestions that might be useful for future studies.

Thrombolytic therapy in refractory unstable angina: the role of Holter monitoring.

We tested the safety and the usefulness of intravenous urokinase (2 million units administered over 30 min) in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-h Holter monitoring (Phase 1) despite maximal medical therapy. After thrombolysis, recurrence of ischemia was observed during a week of observation in the CCU, including two 24-h Holter monitorings at the beginning and the end of the week (Phase 2). Seventeen patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 19 patients had refractory angina or a major cardiac event [10 patients underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) for refractory angina (p less than 0.001), 6 other patients with refractory angina continued medical therapy, one patient had a myocardial infarction, and two patients died]. In Phase 1 the duration of total ischemia (min/24 h) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). In comparison to Phase 1, duration of total ischemia in Phase 2 was significantly reduced in both groups (16.9 +/- 19.6 vs. 25.4 +/- 17.7; p less than .001). A percent value expressing this variation was calculated for each patient: the variation thus obtained again gave information on the clinical outcome--the greater the reduction, the lower the risk of cardiac events (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ergonovine maleate test detects anginal patients with poorly reproducible exercise tests.

The aim of the study is to evaluate the reproducibility of exercise testing and to determine whether there is any correlation between the reproducibility of exercise test and response to the ergonovine maleate test. Thirty-eight patients with mixed angina and documented coronary artery disease underwent an ergonovine maleate test and four exercise tests on consecutive days in the same basal conditions. The ergonovine test was positive in 20 patients (Group I) and negative in 18 patients (Group II). There were no significant differences in the clinical and angiographic data of the two groups. All 152 exercise tests were positive. The variability of the response of the repeated tests was assessed by means of an analysis of the following parameters: heart rate, blood pressure, rate-pressure product, watts, and minutes were recorded at the onset of ischemia (ST decreases greater than or equal to 0.1 mV). Range (maximal-minimal obtained value), ratio between range and maximal obtained value, and coefficient of variation (standard deviation/mean of the four parameters) were calculated for each patient. The analysis of these values demonstrated that while the test was reproducible in some patients, a high individual variability was present in others. Moreover, the individual variability results were higher in Group I than in Group II, with a statistically significant difference for all considered parameters. In conclusion, it is possible to have a poorly reproducible exercise test in patients with mixed angina. The correlation between a positive ergonovine test and a poorly reproducible exercise test suggests that abnormal coronary vasomotion may sometimes be present during exercise and may affect the reproducibility of the test.

[Systemic fibrinolysis in patients with refractory unstable angina]. / Fibrinolisi sistemica in pazienti con angina instabile refrattaria.

We tested the safety and the usefulness of intravenous fibrinolysis in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-hour Holter monitoring (phase 1) despite maximal medical therapy. After fibrinolysis, recurrence of ischemia was recorded during 1 week of observation in CCU including 2 24-hour Holter monitoring at the beginning and at the end of this week (phase 2): 17 patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 patients continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 10 patients underwent CABG or PTCA for refractory angina, 6 other patients with refractory angina continued medical therapy, 1 patient had a myocardial infarction and 2 patients died (p less than 0.001). Phase 1: the duration of total ischemia (min/24 hours) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). Phase 2: in comparison with phase 1, duration of total ischemia was significantly reduced (p less than 0.001). A percent value expressing this variation was calculated for each patient: (min of ischemia in phase 2 - min of ischemia in phase 1/min of ischemia in phase 1). The variation thus obtained again gave information on the clinical outcome: the greater was the reduction, the lower was the risk of cardiac events (p less than 0.001). Our data suggest that: clinical stabilization may be obtained with the addition of fibrinolysis to conventional treatment; Holter monitoring bears prognostic information helpful in identifying patients who need further intervention.

Intravenous nifedipine prevents ergonovine-induced myocardial ischemia in patients with stable effort angina.

Twelve of 40 consecutive patients with effort angina, documented coronary artery disease, and a positive exercise stress test had a positive ergonovine test. ST-segment depression (0.1 mV) occurred in ten and ST elevation (0.1 mV) in two patients. During the ergonovine maleate test the rate-pressure product recorded at the onset of ischemia (ST greater than or equal to 0.1 mV) was significantly lower than that recorded during the exercise stress test. The reproducibility of the rate-pressure product at ischemia was displayed in every patient with a second test; then, a third test after intravenous nifedipine infusion (1 mg over 5 minutes + 1 mg over 55 minutes) was performed. Six patients had negative results; out of the remaining six, three exhibited a significant increase in the dosage required for provoking ischemia. Both systolic and diastolic blood pressure were reduced by nifedipine, while only a slight increase in heart rate occurred, so that the rate-pressure product at any ergonovine dosage was decreased by nifedipine. No differences in the ischemic threshold during exercise and during the ergonovine maleate tests (in washout and after nifedipine) were found in patients with a positive or negative response to nifedipine. The ergonovine test was positive in a sizable (30%) number of patients with stable effort angina. In these patients nifedipine was effective in preventing ergonovine-induced myocardial ischemia.