Autoinduction and steady-state pharmacokinetics of carbamazepine and its major metabolites.

1. The effect of carbamazepine (CBZ) dose change on mean plasma concentrations of CBZ, its two metabolites and apparent steady-state clearance was studied in 77 affectively ill patients receiving CBZ at doses of 100-1200 mg day-1. 2. Autoinduction of CBZ metabolism appeared to be complete within 1 week of starting CBZ therapy or dose change, and its degree was linearly related to CBZ daily dose. 3. Curvilinear plots were obtained for steady-state concentrations of CBZ and its -10,11-epoxide metabolite, and for the ratio of CBZ-10,11-epoxide to CBZ level, versus daily dose of CBZ. 4. On the contrary, steady-state concentration of CBZ-10,11-diol increased proportionately with the dose. This indicates that there is no dose dependency in absorption of CBZ, and that dose-dependent autoinduction of CBZ metabolism is the main cause of the curvilinear relationship between dose and steady-state concentration of CBZ and its intermediary metabolite, CBZ-10,11-epoxide.     

Nonsecretory IgD-Kappa Multiple Myeloma in a Patient with Gaucher's Disease

A patient with Gaucher's disease and non-secretory multiple myeloma is described. The presence of typical Gaucher and myeloma cells was confirmed by transmission and scanning electron microscopy. The immunological studies established the diagnosis of ‘non-secretory’ type of multiple myeloma.     

Familial Mediterranean Fever — A congenital disorder of exaggerated response to endogenous interferon?

Familial Mediterranean Fever (FMF) is an inherited disease whose pathogenesis is obscure. We raise the possibility that the short episodes of fever, joint pains and the abdominal manifestations of this entity may be related to a genetic defect in the interferon system of these patients.     

Duration and outcome of persistent candidaemia in newborn infants

The aims of the study were to define the duration of candidaemia in newborn infants and to determine the incidence of persistent hospital-acquired candidaemia and its associated morbidity and mortality compared with non-persistent candidaemia. This retrospective study, included 56 neonates admitted to the neonatal intensive care unit from 1996 to 2000 who had one or more positive blood cultures for Candida spp. The most prevalent pathogen was Candida albicans (64.3%). Mean disease duration was 6.9 +/- 5.5 days (median 6 days). Twenty-nine patients (52%) had a positive blood culture for >5 days (persistent candidaemia). There were no statistically significant differences between the infants with persistent and non-persistent candidaemia in background or predisposing clinical factors. Fungal endocarditis was present in four patients (13.7%) with persistent disease and one patient (3.7%) with non-persistent disease (odds ratio 4.19), and uveitis developed in one patient. Ten patients (17.8%) died--five with persistent and five with non-persistent disease (P = 1.0). These findings indicate that persistent neonatal candidaemia may be associated with an increased risk of Candida endocarditis, but not with other complications or increased mortality.     

Familial cryoglobulinemia and C4 deficiency

The coexistence of cryoglobulinemia and C4 deficiency was found in one family. Twelve subjects were examined, most of them being asymptomatic. Cryoglobulins were found in 9 members and its type was defined in 6 of them, 3 having mixed IgM-IgG and 3 having monoclonal IgM cryoglobulins. The concentration of the third component of the complement system was normal in 10 subjects, while the concentration of the fourth one was found to be below the lower limit of normal in 9 subjects. Only C4 deficiency--and not cryoglobulinemia--was HLA-linked. There was no evidence of HBs antigenemia. The results of this study are discussed in the light of the pertinent literature.