I n the recent Lescol Intervention Prevention Study (LIPS), long-term therapy with fluvastatin decreased the incidence of cardiac events in patients who underwent percutaneous coronary intervention. 1 The present study analyzed the results of LIPS to investigate (1) the effect of baseline renal function on occurrence of long-term adverse events, (2) whether therapy with fluvastatin decreased the expected hazardous effect of renal impairment, (3) the effect of fluvastatin on renal function during follow-up, and (4) the relation between changes in renal function over time and the occurrence of adverse events. METHODS Study design and patient population:The study design and primary results of LIPS have been described elsewhere. 1 Briefly, after a first successful percutaneous coronary intervention (residual stenosis Ͻ50%, absence of postprocedural in-hospital myocardial necrosis, repeat revascularization, or death), patients were randomized to receive fluvastatin therapy (Lescol, Novartis Pharma AG, Basel, Switzerland; 40 mg 2 times daily) or placebo for 3 to 4 years.At enrollment, patients had to fulfill Ն1 of the following lipid profile criteria: (1) total cholesterol level of 135 to 270 mg/dl with a fasting triglyceride level Ͻ400 mg/dl, (2) total cholesterol level Ͻ212 mg/dl for patients whose lipids levels were measured 24 hours to 4 weeks after an episode of myocardial infarction, or (3) total cholesterol level Ͻ232 mg/dl for patients who had diabetes mellitus. Exclusion criteria included a baseline serum creatinine value Ͼ1.8 mg/dl. The study protocol was approved by the local ethics committees, and all patients gave informed written consent.Lipoproteins and evaluation of renal function: Each patient was clinically evaluated Ն8 times after randomization. Blood lipid levels were measured at all visits, and serum creatinine was measured at baseline

In patients with stable coronary artery disease treated with moderate doses of atorvastatin, carotid IMT regression correlated with changes of inflammation, thrombosis and endothelial activation profiles.

A novel class of histamine receptors (H3), controlling histamine synthesis and release, was described in rat and human brain and peripheral nerve endings. The present study was undertaken to evaluate whether H3 receptors contribute to the regulation of histamine release from human basophils. Basophil leucocytes were incubated with a H3 antagonist (thioperamide; concentrations ranging from 1 nM to 10 microM) or with a H3 ((R)alpha methyl-histamine; concentrations ranging from 1 to 100 mM), and subsequently were stimulated with optimal doses of anti-IgE and formyl-methionyl-leucyl-phenyl-alanine (f-met peptide). No significant modifications of histamine release were observed after incubation either with the H3 agonist or with the H3 antagonist. By contrast, a H2 antagonist (cimetidine; concentrations ranging from 1 to 100 microM) exerted a dose-dependent enhancing effect on anti-IgE- and, to a lesser extent, on f-met peptide-induced histamine release. A H1 antihistamine (chlorpheniramine; concentrations ranging from 100 nM to 1 microM), at the highest concentration employed, displayed an inhibitory activity on IgE-dependent and IgE-independent histamine release. Exogenous histamine was shown to exert a dose-dependent inhibitory effect on two-staged anti-IgE-induced histamine release. Taken as a whole, these results suggest that H3 receptors are not involved in the regulation of histamine release from human basophils; by contrast, H2 receptors participate in controlling histamine release from human basophils, as previously demonstrated by other authors.

No abstract

Bortezomib-dexamethasone (bort-dex) is effective for relapsed/refractory (R/R) multiple myeloma, but few data are available for elderly patients. The aim of this study was to evaluate efficacy and toxicity of bort-dex in elderly R/R MM patients. We evaluated 81 R/R MM patients treated with bort-dex. Eight of them had light-chain disease. The median age of the patients was 73 years (range 65-89 years). All patients were R/R MM patients and had been treated with melphalan and prednisone with or without thalidomide or bortezomib in the first line or with lenalidomide and dexamethasone in the second line. The median number of previous lines was 2. Thirty-nine (48%) patients received bortezomib intravenously and 42 (52%) patients received bortezomib subcutaneously. The median number of bort-dex cycles was 6 (range 1-11). Fifty-three (65.4%) patients achieved at least a partial response, including eight (11%) patients with complete response and nine (12.5%) patients with very good partial responses. The median duration of response, time to next therapy and treatment-free intervals were 8, 11 and 5 months. Duration of response was significantly longer for patients achieving complete response/very good partial response than for those achieving partial response (7.3 vs. 3.8 months, P=0.03). After a median follow-up of 24 months, 78 patients showed disease progression and 70 died. The median time to progression, progression-free survival and overall survival were 8.9, 8.7 and 22 months, respectively. Peripheral neuropathy occurred in 38 (47%) patients. Our data highlight that bort-dex is effective and tolerable in fit elderly patients, thus justifying the efforts for deeper responses. However, awareness of short-lived responses to bort-dex should lead to a thorough evaluation of the need for maintenance.