Efficacy and safety profile of amifostine in the preoperative combined therapy of esophageal cancer patients.

The aim of this study was to assess the protective effect and the safety profile of amifostine in 16 esophageal cancer patients undergoing neoadjuvant chemo-radiation therapy (group A) compared to 21 matched patients (group B), treated with the same schedule without receiving amifostine, and considered as controls. Haematological and extra-haematological toxicity were evaluated according to WHO criteria and considered as result of amifostine activity. The bone marrow toxicity was globally lower in group A than in group B. We recorded 4 cases of mucosities in group B compared to 1 case in group A. amifostine-related side effects were few (2 cases of hypotension and 1 of vomiting), mild, and well controlled. In conclusion, amifostine seems to be effective and safe when used as protective agent also in esophageal cancer.

Amifostine: A selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity (Review).

Patients receiving systemic cancer chemotherapy must often have their dose intensity of therapeutic agents reduced, because a broad range of organs are adversely affected. Therefore, research and the development of agents protecting the normal tissues from the toxicity of antineoplastic therapy, without reducing the antitumour efficacy, are very important. Amifostine, a prodrug that forms an activated free thiol, when dephosphorylated by alkaline phosphatase, appears selective in its entry in non-malignant cells, and exerts a protective effect from toxicity induced by chemo- or radiotherapy on normal tissues, through free radical scavenging, hydrogen donation and inhibition of DNA damage. Studies in vitro and experimental models have confirmed the protective properties of amifostine in normal cells. In clinical trials pretreatment with amifostine reduced the frequency of cyclophosphamide induced neutropenia and nephro-, oto- and neurotoxicity of platinum compounds. In some cases the use of amifostine have also potentiated the effects of several drugs, such as alkylating agents and, in recent studies, taxanes. The main potentially dose-limiting adverse effect is hypotension, that is often asymptomatic. Amifostine is thus usefully employed in order to obtain a better quality of life in patients receiving oncologic treatments.

[Anthracycline-induced cardiotoxicity: monitoring and prevention of the lesion]. / Cardiotossicità da antracicline: monitoraggio e prevenzione del danno.

Doxorubicin is a common antitumoral agent, widely used to treat patients with a variety of neoplastic diseases: acute and severe dose-related chronic cardiotoxicity is the major limitation to optimal use of anthracycline antibiotics. Cancer patients with clinically important heart disease are thus generally not eligible for anthracycline therapy. This review discusses the clinical aspects and possible underlying pathogenetic mechanisms of cardiac damage. Also described is the diagnostic evaluation necessary for early warning of a cardiac event during anthracycline therapy as well as the means to prevent it. The authors also discuss the anthracycline derivatives, verapamil, and dexrazoxane (ICRF-187), a new cardioprotector agent.

Hysterosalpingography and laparoscopy in the study of infertile women.

The Authors confront the data obtained from HSG and laparoscopy carried out in women with sterility problems to evaluate the diagnostic validity of each one of these investigations. There is agreement between the results of both methods in 74.19% of the patients. They think that, for a conclusive evaluation of the tubal factor in infertility, laparoscopy is most useful.

[Neonatal hypophosphatasia (author's transl)]. / Ipofosfatasia neonatale.

A case of severe neonatal hypophosphatasia is reported; X-ray aspects are described and differential diagnosis with other forms of foetoneonatal dwarfism is discussed.

[Changed etiopathogenic and clinical features of infective endocarditis]. / Mutati aspetti etiopatogenetici e clinici dell'endocardite infettiva.

The authors report their experience on etiological and clinical aspects of infective endocarditis (IE). A series of 182 consecutive patients, including 83 cases of medical IE, 73 cases of IE in intravenous drug abusers (DA), 22 cases of IE on late prosthetic valves and 4 cases of IE on early prosthetic valves were evaluated since 1976. Medical IE occurred frequently in the elderly patients and in most of the cases (80%) involved natural valves with underlying abnormalities, either rheumatic (42%) or degenerative (33%) or malphormative (25%). Pre-existing valvular pathology was not needed for IE in DA, occurring in 13%, mainly due to a previous IE. In most of the cases IE in DA was a staphylococcal IE (80%) and a right-sided IE (77%). Streptococci were frequent agent both in medical and late prosthetic valves IE (55%): however, a wide pattern of microorganisms, including "unusual" pathogens like nutritionally variant Streptococci, Haemophylus parainfluenzae, Haemophylus paraphrophylus, Coxiella burnetii and the so-called "non pathogen microorganisms" (e.g. Neisseria sicca) was identified as etiological agent. As regards the clinical approach and diagnosis, the Authors underline some atypical clinical presentations of IE: the pulmonary presentation, occurring in right-sided IE, mainly in DA; the neurological presentation, suggesting staphylococcal etiology and left-sided IE; the vasculitis presentation, miming connective tissue diseases; the cardiac presentation, observed in aortic localization (1 case). One or more severe complications occurred in 65% of the patients, contributing to adverse outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans.

AIM: To investigate in vivo the intermediate cytoskeletal filaments desmin and vimentin in myocardial tissues from patients with dilated cardiomyopathy, and to determine whether alterations in these proteins are associated with impaired contractility. METHODS: Endomyocardial biopsies were performed in 12 patients with dilated cardiomyopathy and in 12 controls (six women with breast cancer before anthracycline chemotherapy and six male donors for heart transplantation). Biopsy specimens were analysed by light microscopy and immunochemistry (desmin, vimentin). Myocyte contractile protein function was evaluated by the actin-myosin in vitro motility assay. Left ventricular ejection fraction was assessed by echocardiography and radionuclide ventriculography. RESULTS: Patients with dilated cardiomyopathy had a greater cardiomyocyte diameter than controls (p < 0.01). The increase in cell size was associated with a reduction in contractile function, as assessed by actin-myosin motility (r = -0.643; p < 0.01). Quantitative immunochemistry showed increased desmin and vimentin contents (p < 0.01), and the desmin distribution was disturbed in cardiomyopathy. There was a linear relation between desmin distribution and actin-myosin sliding in vitro (r = 0.853; p < 0.01) and an inverse correlation between desmin content and ejection fraction (r = -0.773; p < 0.02). Negative correlations were also found between myocardial vimentin content and the actin-myosin sliding rate (r = -0.74; p < 0.02) and left ventricular ejection fraction (r = -0.68; p < 0.01). CONCLUSIONS: Compared with normal individuals, the myocardial tissue of patients with dilated cardiomyopathy shows alterations of cytoskeletal intermediate filament distribution and content associated with reduced myocyte contraction.