The use of unfixed bone marrow trephines for multicolour flow cytometry.

An adequate bone marrow aspirate is essential for a rapid diagnosis of acute leukaemia by multicolour flow cytometry enabling the simultaneous assessment of multiple antigens on the cell surface as well as intracellular or nuclear ones. In the context of acute leukaemia, it is important to have a diagnosis of the blasts lineage as soon as possible to decide the appropriate treatment. This is sometimes delayed due to difficulties in obtaining a bone marrow aspirate due to a "dry tap". In this study we evaluated retrospectively cell markers results by flow cytometry of unfixed bone marrow trephines of 65 patients with leukaemia at diagnosis and including a few after treatment. Our aims were: 1) To compare cell markers results between bone marrow trephine (BMT) and bone marrow aspirate (BMA) 24 cases and BMT with peripheral blood (PB) 14 cases in paired samples to establish if they were reproducible with results of the unfixed bone marrow trephine biopsies. 2) To ascertain a precise diagnosis in 27 (42%) of the cases in which only a bone marrow trephine was available. We demonstrated that unfixed bone marrow trephine provides an adequate and representative cell suspension for flow cytometry and it is a powerful tool when no other material (bone marrow aspirate or peripheral blood) is available to make a rapid diagnosis. Furthermore when marrow aspirate or peripheral blood paired samples were available, flow cytometry results obtained were identical across all the sample types. Applicability to the clinical laboratory: We described a method to obtain a cell suspension from core biopsies that can easily be implemented routinely in a laboratory that performs diagnostic flow cytometry immunophenotyping. This method is simple, inexpensive and it doesn't require extra equipment.

Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service.

Therapeutic drug monitoring data of the new atypical neuroleptic drug olanzapine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of concentration/daily dose (C/D; ng/mL per mg/d) of olanzapine was compared in three groups: patients treated with olanzapine (n = 134), patients treated with olanzapine plus fluvoxamine (n = 10) concomitantly, and patients treated with olanzapine plus sertraline (n = 21) concomitantly. No significant difference was seen between the olanzapine and the olanzapine plus sertraline groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the mean 2.3-fold higher than patients receiving olanzapine without additional fluvoxamine. This indicated that fluvoxamine inhibits the metabolism of olanzapine, probably because of inhibition of cytochrome P450 (CYP) 1A2, whereas sertraline is unlikely to interfere with the metabolism of olanzapine. Combination therapy of olanzapine and fluvoxamine should be used cautiously, and therapeutic drug monitoring should be instituted to avoid olanzapine-induced adverse effects or intoxications.

[Morphometric studies on numerical area density of glomerular cells (nuclear section) in the pathogenetic evaluation of minimal glomerular abnormalities]. / Morphometrische Untersuchungen zur numerischen Flächendichte glomerulärer Zellen (Kernanschnitte) für die pathogenetische Wertung geringer glomerulärer Abnormitäten.

Minor glomerular abnormalities (MGA) with hypercellularity (according to the WHO-nomenclature) are one of the most frequent glomerular lesions. Minimal proliferative changes in the glomerular structure can be proven only with the aid of morphometric methods. Morphometric glomerular studies were carried out in MGA with hypercellularity and with rare or minor deposits of immunoglobulins and/or complement (C3) or without deposits. Clinical symptomatology was variable (minimal to mild proteinuria, massive proteinuria, haematuria or haematuria with proteinuria). The groups examined were divided as follows: MGA without deposits and with minimal (mild) proteinuria. MGA with minor deposits and with minimal (mild) proteinuria. These two groups were statistically compared with: normal glomerular structure (after Wehner 1974); MGA with massive proteinuria or nephrotic syndrome (includes the minimal changes with nephrotic syndrome), which showed minor deposits of complement; diffuse mesangial proliferative glomerulonephritis (IgA-nephritis). The glomerular cell density, i.e. the total number of glomerular cells, averaged 3.48 cells/1,000 micron 2 in the first group and 4.26 cells/1,000 micron 2 in the second group. In normal renal corpuscles the average was 2.30 cells/1,000 micron 2. The first group has an average of 51% and the second group has an average of 84% higher cell density than normal renal corpuscles. The cell density in diffuse mesangial proliferative glomerulonephritis (IgA-nephritis) is increased by 160% compared with the norm. The first group was not statistically different in cell density from MGA with high proteinuria. We conclude, that MGA with hypercellularity and minimal to mild proteinuria represents a minimal mesangial proliferative glomerulonephritis.