Roberto Lerza

MYELODYSPLASTIC SYNDROME ASSOCIATED WITH INCREASED BONE MARROW FIBROSIS AND TRANSLOCATION (5;12)(q33:p12·3)

In primary myelodysplastic syndromes (MDS ) striking myelofibrosis with collagenization is unusual (Tricot rt nl. 1984: Pagliuca rt al, 1989; Lambertenghi-Deliliers rt nl. 199 1 : Verhoefet al, 1991). We report on a patient with primary MDS. leucoerythroblastosis. a n uncommon chromosomal abnormality and diffuse bone marrow fibrosis with areas of collagenization. In August 1989 the patient, a 52-year-old white male. had been found to have haemoglobin of 8.6 g/dl with normal leucocyte and platelet counts. The bone marrow aspirate was hypercellular with granulocytic hyperplasia, normal megakaryopoiesis and erythroid hypoplasia and dysplasia. Neither splenomegaly nor chromosomal abnormalities were observed. A diagnosis of refractory anaemia was made: the patient remained asymptomatic for 16 months. In December 1990 no pathological findings were observed except for a mildly enlarged liver: ecotomography confirmed the normal size of the spleen. A thorough search for primitive or metastatic cancer yielded no result. For peripheral blood parameters see Table I . On peripheral blood cells a clonal

The in vitro and in vivo effect of recombinant interferon α‐2a on circulating haemopoietic progenitors in polycythaemia vera

In four patients with polycythaemia vera (PV) who received interferon alpha (IFN‐α) (3 MU subcutaneously three times a week) for 5 months, peripheral blood levels of granulocyte‐macrophage colony‐forming units and erythroid burst‐forming units were assessed monthly. Circulating progenitors significantly decreased throughout the treatment period. Moreover, we observed an inhibitory activity of IFN‐α on haemopoietic progenitor cells (HPC) from patients with PV in vitro.

Regional pharmacokinetic selectivity of intrapleural cisplatin

The pharmacokinetics and toxicity of cisplatin were investigated in 3 patients affected by malignant mesothelioma who received 90 mg/m2 of the drug intrapleurally. The mean area under the pleural Pt concentration versus time curve (AUC) [12.83 (S.D. 4.06) mg.min/ml] was about 50 times greater than that detected in plasma [0.27 (0.03) mg.min/ml], indicating a clear pharmacological advantage for this route of administration. The mean plasma total Pt concentration was 1.1 micrograms/ml and the apparent total body clearance was 268 (101) ml/min. Platinum plasma pharmacokinetic data measured following intrapleural cisplatin administration (4 patients) were compared with those observed in 7 patients treated intravenously with the same dose of cisplatin (90 mg/m2) under the same modalities of hydration. Intrapleural administration of cisplatin resulted in significantly lower plasma total partial AUC (P less than 0.05) and prolonged plasma levels of filterable Pt compared with intravenous administration. No difference between the two routes of cisplatin administration in the renal clearance (S.D.) of filterable Pt [132 (64) ml/min and 122 (39) ml/min for intravenous and intrapleural cisplatin, respectively] were observed. None of the mesothelioma patients developed clinical symptoms or signs of pleural inflammation. The intrapleural treatment did not produce haemotoxicity and the emetic toxicity was lower compared with that observed in patients receiving cisplatin intravenously.

Adenosine in the treatment of supraventricular tachycardia: 5 years of experience (2002-2006).

We report a retrospective analysis of 5 years of adenosine use in our emergency department (2002-2006). We treated 454 patients with an intravenous bolus of adenosine. The cohort was made up of 40.7% men and 59.3% women, with mean age of 47.32 years, mean heart rate of 162.48 beats per minute. Among them, 73% responded immediately to the 6-mg dose, 15% responded after the second 12-mg dose, and 11% responded to a further 12-mg dose, whereas 11% were unresponsive. We observed minor side effects in a high percentage of patients (ie, chest tightness 83%, flushing 39.4%, sense of impending death 7%). Only 1 major adverse effect was recorded, that is, administering 12 mg of adenosine induced a marked acceleration in the ventricular rate of a patient with an undiagnosed atrial flutter, caused by induction of atrioventricular conduction (1:1). Our results confirm that when patients are appropriately selected, adenosine is probably the best available drug to treat paroxysmal supraventricular tachycardias, especially in emergency situations.

Dexamethazone-induced acute tumor lysis syndrome in a T-cell malignant lymphoma.

We report a case of steroid-induced acute tumor lysis syndrome and review the literature. A 60-year-old woman was started on steroid therapy for dyspnea due to bilateral pleural effusion and a large mass involving the anterior mediastinum. The final diagnosis was precursor T-lymphoblastic lymphoma-leukemia. Following steroid therapy, the patient developed acute renal failure and laboratory evidence of metabolic changes induced by massive cytolysis. She received vigorous hydration, diuretic and allopurinol therapy, and haemodialysis. Her diuresis, renal function and laboratory data returned to normal within 2 weeks. A review of the medical literature on T-cell lymphoma revealed only one similar case of steroid-induced acute tumor lysis syndrome, a life-threatening metabolic emergency. This risk should be kept into account in the management of patients with lymphoproliferative disorders.

Splenectomy induced complete remission in a patient with multicentric Castleman's disease and autoimmune hemolytic anemia

Abstract Castlemans disease (CD) is a rare disorder of the lymphoid tissue in which the clinical manifestations often mimic a malignant lymphoma. Despite the absence of monoclonality of the lymphoid proliferation, the multicentric variant of the disease (MCD) is characterized by severe symptoms and poor prognosis. Etiologic, pathogenetic, and therapeutic aspects of MCD are still uncertain. We report the case of a 57-year-old patient affected by MCD complicated by severe immunohemolytic anemia. Whereas the clinical and laboratory response to steroids and chemotherapeutic agents was only partial, splenectomy induced a complete remission of hemolysis and disappearance of the constitutional symptoms and of all generalized lymphadenopathies.

Minor head injury in the elderly at very low risk: a retrospective study of 6 years in an Emergency Department (ED)

INTRODUCTION Mild head injury (MHI) is a common clinical problem in emergency departments (EDs). Long-standing debate is still going on about MHI in the elderly: current guidelines recommend to perform a CT scan on this group. MATERIALS AND METHODS We performed a retrospective study by reviewing patients older than 65 years, evaluated in our ED for which a CT scan of the head was performed for MHI, between 2004 and 2010. According to Italian Guidelines, we considered only patients with low-risk MHI. RESULTS We considered 2149 eligible patients: we recorded 47 pathological acute findings on CT scan (2.18%), but only 3 patients (0.14%) underwent neurosurgery. We analysed our patients according to different age groups: in patients in the 65- to 79-year-old group, we documented pathological findings on CT in 0.66% of cases, with a significant increase in the group older than 80 years, with a rate of 3.33% of acute findings on CT (OR 5.22, P < .001); 617 patients were on antiplatelet therapy: 22 of these patients (3.72%) had a pathological finding on CT scan (OR 2.23, P < .005). DISCUSSION Our retrospective analyses demonstrated that the incidence of intracranial complications after MHI is not different from that of the general population, and based on this finding, a CT does not seem to be necessary, at least up to 80 years old. Our data suggest that antiplatelet therapy could be a significant risk factor. Our results suggest that elderly patients between 65 and 79 years old without risk factors could be managed as younger patients.

Preclinical in vitro evaluation of hematotoxicity of the cisplatin–procaine complex Dpr

We evaluated in vitro the inhibitory effect of cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR) on colony formation by granulocyte/macrophage (CFU-GM) peripheral blood progenitor cells, representing a method to quantitate the toxicity of drugs to the hematopoietic system, and human leukemic cell lines. The results were compared with those obtained exposing cells to cisplatin and carboplatin. Our data showed that while DPR had a significantly better cytotoxic activity than cisplatin and carboplatin against HL60 and K562, and than carboplatin against Molt 4 cells, it showed 12 and 43 times less inhibitory effect on CFU-GM than cisplatin and carboplatin, respectively. These results suggest that the myelosuppressive activity of DPR could be lower than that of cisplatin and carboplatin, and, furthermore, that leukemic cells represent a preferential target for its cytotoxic activity compared to normal committed hemopoietic progenitor cells. All our results speak in favor of a better therapeutic index for DPR than for the other platinum compounds considered here.

Failure of N-acetylcysteine to protect against cis-dichlorodiammine-platinum(II)-induced hematopoietic toxicity in mice

In view of the results showing a decrease in cis-dichlorodiammineplatinum(II) (cis-DDP) nephrotoxicity after administration of thiol donors, this study was carried out to test the possibility that N-acetylcysteine (NAC) was active against myelodepressive effects of the anticancer drug. Cis-DDP (15.5 mg/kg body weight, i.v.) was administered to control mice and to mice treated simultaneously or 1 h later with NAC (800 mg/kg body weight, i.v.). At various times after treatment, up to 11 days, assessments were made of peripheral blood cell levels and bone marrow progenitor cell (CFUs and CFUc) concentrations. Cis-DDP caused a decrease in hemopoietic precursor cells in the order of that caused by other hemopoietic precursor cells in the order of that caused by other myelodepressive drugs, whereas there was only a slight decrease in peripheral blood WBC. In this experimental setting, NAC administration did not afford significant protection against platinum toxicity on bone marrow precursors or peripheral blood cells.

Intracranial complications after minor head injury (MHI) in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs)

Introduction: The correlation between chronic direct oral anticoagulants (DOACs) intake and the incidence of intracranial complications after minor head injury (MHI) is still not well defined. This study examined the incidence of complications in patients receiving vitamin K antagonists (VKA) or DOACs observed in the emergency department (ED) for MHI. Methods: Two hundred twenty‐five patients affected by MHI and receiving oral anticoagulants were recorded between January and December 2016, distinguishing those treated with VKA (118) from those receiving DOACs (107). All patients underwent a CT scan and were observed for 24 h in the ED. Follow‐up was performed up to 1 month after the head trauma. Results: The rate of intracranial hemorrhage was significantly lower in patients treated with DOACs than in patients treated with VKA. We recorded 2 deaths among the 12 patients who experienced intracranial complications in the VKA group. Discussion: DOACs seem to have a more favorable safety profile than VKA in patients affected by MHI. This observation is important in light of the increasing number of elderly patients who are receiving anticoagulant therapy.