Cerebral rhabdomyosarcoma with rhabdoid tumor-like features

The present paper describes a case of cerebral neoplasm presenting histological-immunohistochemical characteristics of malignant rhabdoid tumor (MRT) and ultrastructural featuresof both MRT and rhabdomyosarcoma (R). MRT was first described as an aggressive neoplasm of unknown histogenesis of the kidney, then many other sites of onset were reported, including the central nervoussystem. However, it has been shown that other tumors of known histogenesis can mimick histologic and ultrastructural features of MRT. On the basis of our findings we agree with authors whosupport the notion that extrarenal MRT has often a different histogenesis from MRT of kidney, and it probably is a phenotypicentity rather than a distinct pathologic entity.     

The endocannabinoid 2-arachidonylglycerol decreases the immunological activation of Guinea pig mast cells: involvement of nitric oxide and eicosanoids

The antigen-induced release of histamine from sensitized guinea pig mast cells was dose-dependently reduced by endogenous (2-arachidonylglycerol; 2AG) and exogenous [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP55,940)] cannabinoids. The inhibitory action afforded by 2AG and CP55,940 was reversed by N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), a selective cannabinoid 2 (CB(2)) receptor antagonist, and left unchanged by the selective CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). The inhibitory action of 2AG and CP55,940 was reduced by the unselective nitric-oxide synthase (NOS) inhibitor N-monomethyl-L-arginine methylester (l-NAME) and reinstated by L-arginine, the physiological substrate. The inhibitory action of 2AG and CP55,940 was also reduced by the unselective cyclooxygenase (COX) inhibitor indomethacin and the selective COX-2 blocker rofecoxib. Both 2AG and CP55,940 significantly increased the production of nitrite from mast cells, which was abrogated by L-NAME and N-(3-(aminomethyl)benzyl)acetamidine (1400W), a selective inducible NOS (iNOS) inhibitor. Nitrite production consistently paralleled a CP55,940-induced increase in the expression of iNOS protein in mast cells. Both 2AG and CP55,940 increased the generation of prostaglandin E(2) from mast cells, which was abrogated by indomethacin and rofecoxib and parallel to the CP55,940-induced expression of COX-2 protein. Mast cell challenge with antigen was accompanied by a net increase in intracellular calcium levels. Both cannabinoid receptor ligands decreased the intracellular calcium levels, which were reversed by SR144528 and l-NAME. In unstimulated mast cells, both ligands increased cGMP levels. The increase was abrogated by SR144528, l-NAME, indomethacin, and rofecoxib. Our results suggest that 2AG and CP55,940 decreased mast cell activation in a manner that is susceptible to a CB(2) receptor antagonist and to inhibition of nitric oxide and prostanoid pathways.     

Cost analysis for the prevention of variceal rebleeding: a comparison between transjugular intrahepatic portosystemic shunt and endoscopic sclerotherapy in a selected group of Italian cirrhotic patients

The aim of the present study was to compare the cumulative cost of the first 18-month period in a selected group of Italian cirrhotic patients treated with transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic sclerotherapy (ES) to prevent variceal rebleeding. Thirty-eight patients enrolled in a controlled trial were considered (18 TIPS and 20 sclerotherapy). The number of days spent in the hospital for the initial treatment and during the follow-up period were defined as the costs of hospitalization. ES sessions, TIPS procedures, angioplasty or addition of a second stent to maintain the shunt patency, were defined as the costs of therapeutic procedures. The two groups were comparable for age, sex, and Child-Pugh score. During the observation period 4 patients died in the TIPS group, and 2 died and 1 was transplanted in the sclerotherapy group. The rebleeding rate was significantly higher in the sclerotherapy group. Despite this, the number of days spent in the hospital was similar in the two groups. This was because of a higher number of hospital admissions for the treatment of hepatic encephalopathy and shunt insufficiency in the TIPS group. The therapeutic procedures were more expensive for TIPS. Consequently, the cumulative cost was higher for patients treated with TIPS than for those treated with sclerotherapy. The extra cost was because of the initial higher cost of the procedure and the difference was still maintained at the end of the 18-month follow-up. When the cumulative costs were expressed per month free of rebleeding, the disadvantage of TIPS disappeared. In conclusion, a program of prevention of variceal rebleeding with TIPS, despite the longer interval free of rebleeding, is not a cost-saving strategy in comparison with sclerotherapy.     

Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma

BACKGROUND AND OBJECTIVES: Few therapeutic options are presently available for patients with multiple myeloma (MM) who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a glutamic acid derivative with anti-angiogenic properties, has been recently proposed as an effective therapy for patients with advanced refractory disease. The aim of this study was to evaluate the activity of thalidomide in a large series of MM patients. DESIGN AND METHODS: From October 1999 to January 2001, 65 patients (46 males/19 females) from 8 Italian institutions were treated with thalidomide. Twenty-six patients had relapsed after autologous stem cell transplantation, either single (n = 12) or double (n= 12); 38 patients had shown disease progression after >= 2 lines of conventional chemotherapy, 2 patients had relapsed after allotransplant, one single patient had not received previous treatment. Sixty-one (93.8%) patients were in stage III, median b2 microglobulin was 2.9 mg/L, and median bone marrow plasma cell infiltration was 50%. Thalidomide was initially administered at a dose of 100 mg/day; if well tolerated, the dose was to be increased serially by 200mg every other week to a maximum of 800 mg/day. RESULTS: The median administered dose of thalidomide was 400 mg/day. WHO grade > II toxic effects were constipation (52%), lethargy (34%), skin rash (11%), peripheral neuropathy (14%) and leukopenia (3%). Sixty patients are presently evaluable for response; of these, 17 (28.3%) showed > or = 50% reduction in serum or urinary M protein concentration and 11 (18.3%) showed > or = 25% tumor reduction, for a total response rate averaging 46.6%. After a median of 8 months' follow-up, 15/28 patients are alive and progression-free (at 2 to 16 months), 12 patients have relapsed, and 1 patient died of pulmonary edema while still in partial remission. Among pre-treatment variables that were analyzed for their potential relationship with tumor response, only the concentration of vascular endothelial growth factor (VEGF) in the conditioned media obtained upon culture of bone marrow plasma cells was statistically significant. Plasma cells from patients who responded favorably to thalidomide secreted a significantly lower amount of VEGF than plasma cells from resistant patients (126.45 165 pg/mL vs 227.11 70 pg/mL, p=0.04). INTERPRETATION AND CONCLUSIONS: These data confirm that thalidomide is active in patients with advanced relapsed/refractory MM and represent the basis for ongoing clinical trials aimed at testing the role of this drug as front line therapy for newly diagnosed disease.     

Comparison of the high-dose dipyridamole-echocardiography test and exercise two-dimensional echocardiography for diagnosis of coronary artery disease

Fifty-five patients with effort angina pectoris and technically satisfactory baseline echocardiograms performed a supine exercise-echocardiography test (EET) and a high-dose dipyridamole-echocardiography test (DET, up to 0.84 mg/kg of intravenous dipyridamole in 10 minutes). All underwent coronary arteriography, which showed that at least 1 major artery had more than 70% stenosis in 34 patients. For each patient, the same physician performed both tests, with the same echocardiographic equipment. Detection of new onset or worsening regional asynergy was the only criterion of positivity for both tests. DET yielded interpretable studies in all 55 patients (100%); EET yielded only 40 such studies (73%) (p less than 0.01). In the 40 patients in whom both tests were interpretable, DET showed, compared with EET, a similar sensitivity (72% vs 76%) and specificity (100% vs 87%) (difference not significant for both) for detecting angiographically assessed coronary artery disease. In the 16 patients in whom both DET and EET yielded positive responses for ischemia, the same myocardial region showed reversible asynergy. Thus, independent of all factors that can affect the performance of each test (operator, patient and instrumentation), DET was significantly more feasible than EET, with comparable sensitivity and specificity. Dipyridamole provokes asynergy in the same regions that show ischemia during exercise.     

Comparison of lidoflazine and quinidine in the conversion to sinusal rhythm in atrial fibrillation of recent onset

In order to compare the efficacy of oral lidoflazine (240 mg/die) and oral quinidine (1200 mg/die) in re-establishing sinus rhythm, we studied 115 patients (mean age 63.8 years; range 32-91) with atrial fibrillation of recent onset (less than 3 months). Patients with cardiac failure, acute myocardial infarction, severe intraventricular conduction disturbances, kaliemia less than 3.8 mEq/L or digoxinemia greater than 2 ng/ml were not included. Patients were randomly given one of the 2 drugs, until conversion to sinus rhythm was achieved, severe side effects occurred or for a maximum therapy of 5 days. No significant differences were present between the 2 groups in terms of age, male/female ratio, duration of atrial fibrillation, presence of an enlarged left atrium, presence of organic heart disease (or arterial hypertension) or digitalis therapy. Sinus rhythm resumption was obtained in 41/58 (71%) patients treated with quinidine and in 47/57 (82%) patients treated with lidoflazine (p = ns). In successful cases, the mean treatment time was 79 +/- 33 (SD) hours for quinidine and 66 +/- 36 hours for lidoflazine (p = ns). Both drugs showed the same efficacy in 3 subgroups of patients in whom the arrhythmia had different duration (less than 24 hours; between 24 hours and 3 days; more than 3 days). Treatment was stopped in 5 patients receiving quinidine (gastrointestinal side effects) and in 3 patients receiving lidoflazine (frequent premature ventricular beats in 2 and polymorphic ventricular tachycardia of the "torsade de pointes" type in 1).(ABSTRACT TRUNCATED AT 250 WORDS)