A phase I-II trial of 4'-deoxydoxorubicin (esorubicin) in refractory or relapsed acute leukemia

In a phase I-II study, 21 patients with relapsed or refractory acute leukemia were treated with 4'-deoxydoxorubicin (esorubicin), the 4'-deoxy derivative of doxorubicin. Four of 14 evaluable patients with acute nonlymphocytic leukemia (ANLL) in relapse or refractory to other anthracyclines achieved partial response (28.5%). Pharmacokinetics were similar to those of the parent compound, doxorubicin. Esorubicin has activity in ANLL and has pharmacologic properties comparable to those of other anthracyclines. Dose-limiting toxicity occurs in the form of mucositis, which may limit its use in combination with other antileukemic drugs.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

Stimulation der Granulopoese mit hämatopoetischen Wachstumsfaktoren

Die therapieinduzierte Neutropenie kann mit den Kolonie stimulierenden Faktoren (CSF) der Granulopoese (G-CSF und GM-CSF) vermieden,abgemildert oder in ihrer Zeitdauer verkürzt werden. Die CSF erm?glichen die Mobilisation h?matopoetischer Stammzellen in das Blut und deren Sammlung für die Transplantation nach Hochdosistherapie.Diese Faktoren sind daher essenziell in der Supportivtherapie maligner Erkranklungen. Der Arbeitskreis Supportivma?nahmen in der Onkologie (ASO) der Deutschen Krebsgesellschaft hat Richtlinien zur Therapie mit den Kolonie stimulierenden Faktoren entwickelt, die unterschiedlichen klinischen Situationen angepasst sind. Der vollst?ndige Text wurde 12/2001 in “Der Onkologe” publiziert [23], er ist auch auf der Homepage des ASO unter http://www.onkosupport.de zu finden [24]. Prof.Dr. H. Link H?matologie, Internistische Onkologie, Endokrinologie, Medizinische Klinik I, Westpfalz-Klinikum Kaiserslautern, Akademisches Lehrkrankenhaus der Johannes-Gutenberg-Universit?t Mainz, 67653 Kaiserslautern, E-Mail: hlink@westpfalz-klinikum.de     

Improved Performance of Hip DXA Using a Novel Region of Interest in the Upper Part of the Femoral Neck: In Vitro Study Using Bone Strength as a Standard of Reference

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.     

Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH 1 and TH 2 cytokines

Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-γ (IFN-γ), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E₂ (PGE₂). We find that PGE₂ and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH 1 cytokine IFN-γ does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH 1 and TH 2 cytokines, respectively.     

PSEUDOHYPERPHOSPHATAEMIA AND MONOCLONAL GAMMOPATHY

SUMMARY A case is reported of pseudohyperphosphataemia in association with a monoclonal gammopathy of undetermined significance.