Cutaneous plasmacytosis associated with lung and anal carcinomas

Cutaneous plasmacytosis is a rare disorder characterized by a benign proliferation of mature plasma cells that appears as multiple dark-brown to purplish skin lesions, often associated with polyclonal hypergammaglobulinaemia. We present the case of a 55-year-old Caucasian man who suffered from a cutaneous plasmacytosis associated with two different carcinomas. Cutaneous plasmacytosis seems to be a reactive process because most cases reported are not associated with any apparent underlying disease. Nevertheless, because few reported cases were associated with malignancies, screening of additional neoplasms would be justified.     

Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria

Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o.The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients.Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients.In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.     

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.