Effects of the combined treatment with thalidomide, megestrol and interleukine-2 in cirrhotic patients with advanced hepatocellular carcinoma. A pilot study.

BACKGROUND: Thalidomide, an anti-angiogenic agent, does not have a good therapeutic effect for advanced hepatocellular carcinoma when used alone. Megestrol and interleukin-2 have been proposed as a palliative treatment for hepatocellular carcinoma. AIMS.: We assessed the effectiveness/safety of a combined therapy with thalidomide+megestrol+interleukin-2 in cirrhotic patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Nine cirrhotic patients with advanced hepatocellular carcinoma received oral megestrol (160 mg/day) and thalidomide (from 50 mg/day to the maximal tolerated dose). Four patients also received subcutaneous interleukin-2 (1 million U/day for 21 days/month). RESULTS: The maximal tolerated dose of thalidomide was 150 mg/day. All patients complained of sedation and other neurological or digestive adverse effects. In all but one patient the adverse effects disappeared after thalidomide withdrawal or dose reduction. Interleukin-2 administration caused a flu-like syndrome and a reaction at the injection site. During treatment, alpha-fetoprotein increased in six patients, remained stable in two and decreased in one. Eight patients showed tumour progression and one had a stable disease. Eight patients died. The median survival was 9.9 (range 2.6-18.6) months. CONCLUSION: In cirrhotic patients, the combined treatment with thalidomide+megestrol (+/-interleukin-2) does not control hepatocellular carcinoma growth, possibly due to the low tolerance to thalidomide and interleukin-2 preventing the use of appropriate dosages.

Systemic and coronary haemodynamic effects of the new hypotensive drug L 6150.

The acute systemic and coronary haemodynamic effects of a new hypotensive drug L 6150 (3-hydrazino-6-[N,N-bis(2-hydroxyethyl)amino]pyridazine) have been studied in six patients with renal or essential hypertension. The drug, administered intravenously at a dose of 2-9 mg, caused a marked hypotension and increase of cardiac output in five cases. Though left ventricular work was reduced or unchanged after the drug, myocardial blood flow increased markedly, coronary resistance decreased and coronary A-V oxygen difference decreased by about 50% indicating coronary vasodilation. When compared with the available data on the effects of hydrazinophthalazine, L 6150 appeared to have qualitatively similar effects, but a somewhat greater direct coronary vasodilator effect.

[Holter-detected myocardial ischemia. Impact for prognosis and decision making after acute myocardial infarction]. / Ischemia all'Holter. Impatto prognostico e decisionale nel post infarto.

BACKGROUND: Aim of the study was to evaluate the prognostic and decision making value of Holter detected myocardial ischemia after acute myocardial infarction in comparison with clinically detected postinfarction angina and exercise test. METHODS: To this aim the patients consecutively admitted to our coronary care unit with acute myocardial infarction during one year were retrospectively evaluated. One hundred and eighty-nine patients (age 70+/-11 years, 137 male and 51 female) had a 24 hour Holter monitoring. One-year follow up of these patients was obtained. RESULTS: Myocardial ischemia was detected by Holter monitoring in 21 patients (11%), 4 with and 17 without angina. Symptom limited exercise test was obtained before discharge in 116 patients (62%): 45% were positive, 42% non-diagnostic and 13 negative for myocardial ischemia. Post infarction angina was present in 15 patients (9%). Patients with Holter detected myocardial ischemia were older (73+/-10 vs 66+/-11 years, p<0.05) and had higher prevalence of both angina and positive exercise test (p<0.01). One-year follow up was obtained in 186 patients. Holter detected myocardial ischemia positive predictive value for death or reinfarction was 15%, negative predictive value was 90%, similar to the absence of angina (90%) and the absence of positive exercise test (93%). Angina and exercise test identified 62% of patients with Holter detected myocardial ischemia. Residual myocardial ischemia was exclusively observed by Holter monitoring in 4% of the population, particularly in 1 patients with and 7 without exercise test. CONCLUSIONS: The additive contribution of Holter detected myocardial ischemia in the prognosis and decision making of post infarction patients is rather scanty.

[Role of ambulatory ECG in a cardiology department]. / Ruolo dell'ECG dinamico in un Servizio di Cardiologia.

Ambulatory electrocardiographic monitoring has become an important clinical tool for the diagnosis and management of patients with symptoms suggesting cardiac arrhythmias or ischemic heart disease. Holter monitoring (H) is widely used in the evaluation of patients with recent myocardial infarction, angina pectoris, hypertrophic cardiomyopathy, dilated cardiomyopathy, long QT syndrome, sinus node dysfunction. The role of H monitoring in defining prognosis in many of these heart disease is not well established. Holter monitoring is also used to evaluate the results of antiarrhythmic and antianginal drug therapy. Application of quantitative H monitoring to define drug efficacy has revealed that antiarrhythmic drugs may have a proarrhythmic effect and that a withdrawal syndrome can follow the abrupt cessation of antianginal and antiarrhythmic drugs. There are no consistent data about the optimal duration of monitoring to detect and quantify ventricular arrhythmias and ischemic attacks. We think that the appropriate duration of monitoring must be adjusted to the single patient, considering: a) the frequency and severity of symptoms; b) the cardiac lesion (s) and functional class; c) the goal of H. When used appropriately H can be a cost-effective tool and may prevent hospitalizations.

[Dipyridamole-echocardiography test in the diagnosis of vasomotor angina]. / Il test ecodipiridamolo nella diagnosi di angina vaso-motoria.

Dipyridamole-atropine echocardiography testing is used extensively for the diagnosis of coronary artery disease and it is highly effective in diagnosing "organic" coronary artery disease by inducing myocardial ischemia via three different mechanisms: maximal coronary artery vasodilatation with phoenomena of flow-maldistribution caused by dipyridamole, increase in myocardial oxygen consumption and reduction of the oxygen supply to the myocardium caused by atropine. Moreover, the abrupt withdrawal of the coronary artery vasodilatation caused by aminophylline, which is routinely infused at the end of the test, may trigger coronary artery spasms in patients with variant angina, thus enhancing the diagnostic power of the test. We report two clinical cases of patients with rest angina and angiographically normal coronary arteries, in whom coronary artery spasm was induced by administering aminophylline during the stress test.

Palivizumab in infants with gestational age < or = 28 weeks and bronchopulmonary dysplasia.

We report data from 11 patients < or = 28 weeks' gestation with severe bronchopulmonary dysplasia (BPD) prophylactically treated with palivizumab for prevention of respiratory syncytial virus (RSV) infection. All babies were receiving pharmacologic respiratory therapy at the moment of discharge from neonatal intensive care unit. Babies received 15 mg/kg i.m. palivizumab every 4 weeks to a max of 5 doses during the period November-March. We compared them with 8 similar infants that did not require therapy at discharge, nor were given any placebo. The treated infants did not present significant side effects. No baby in both groups was infected with RSV during the period of observation. We conclude from these preliminary data that palivizumab did not present contraindications in infants < or = 28 weeks' gestation with severe BPD requiring pharmacologic therapy at discharge. More data are required to evaluate efficacy to prevent RSV infection in these infants.

The preterm infant's antibody response to a combined diphtheria, tetanus, acellular pertussis and hepatitis B vaccine.

Several combined vaccines have recently been developed, in order to improve the implementation of immunization programmes and increase the coverage for each vaccine. As the response of preterm infants may vary depending on the vaccination schedule and the vaccine product, it should be evaluated specifically as new vaccines become available. In this study we have examined the antibody response to a combined diphtheria, tetanus, acellular pertussis, and hepatitis B vaccine (DTPa-HBV), given as a primary vaccination course at 3, 5 and 11 months of postnatal age, in 34 preterm infants (mean gestational age (GA) = 32.0 weeks) in comparison with 28 term infants. At the end of the primary course, preterm infants had antibody concentrations for pertussis 69 kDa antigen and diphtheria toxoid that were significantly lower than those of term infants; preterm infants with GA < or = 31 weeks had antibody concentrations for pertussis 69 kDa antigen and HBsAg that were significantly lower than those of preterm infants with higher GA; anti-HBs antibody levels correlated with GA. However, the combined DTPa-HBV vaccine elicited seroconversion to all its components in all but two infants, one term and one preterm, after the second dose and a total seroconversion after the third dose. We conclude that preterm infants may be immunized with a combined DTPa-HBV vaccine, starting at the same chronological age, as term infants.