The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and longterm toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups.
Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.
Although the gene defects for several mouse mutants with severe osteopetrosis are known, the genes underlying human infantile malignant recessive osteopetrosis remain elusive. Osteopetrosis is thought to be caused by a defect in osteoclast function. These cells degrade bone material in a tightly sealed extracellular compartment that is acidified by a vacuolar (V)-type H(+)-ATPase. Genes encoding components of the acidification machinery are candidate genes for osteopetrosis. In five of ten patients with infantile malignant osteopetrosis, we now demonstrate five different mutations in OC116, the gene encoding the a3 subunit of the V-ATPase from osteoclasts. Two independent patients were homozygous for mutations that predict a total loss of function by severely truncating the protein. By affecting a splice site, another homozygous mutation deletes 14 amino acids within the N-terminus, which interacts with other subunits of the proton pump. On the other hand, in four patients no mutations were found, and one patient from a consanguineous family did not show homozygosity at the OC116 locus, suggesting that mutations in at least one different gene may underlie osteopetrosis. Our work shows that mutations in the gene encoding the a3 subunit of the proton pump are a rather common cause of infantile osteopetrosis and suggests that this disease is genetically heterogeneous.
While the ancient Egyptians and Greeks used honey for wound care, and a broad spectrum of wounds are treated all over the world with natural unprocessed honeys from different sources, Medihoney™ has been one of the first medically certified honeys licensed as a medical product for professional wound care in Europe and Australia. Our experience with medical honey in wound care refers only to this product. In this review, we put our clinical experience into a broader perspective to comment on the use of medical honey in wound care. More prospective randomized studies on a wider range of types of wounds are needed to confirm the safety and efficacy of medical honey in wound care. Nonetheless, the current evidence confirming the antibacterial properties and additional beneficial effects of medical honey on wound healing should encourage other wound care professionals to use CE-certified honey dressings with standardized antibacterial activity, such as Medihoney™ products, as an alternative treatment approach in wounds of different natures.
Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose and/or intrathecal methotrexate (MTX). Acute toxicity is usually transient without permanent damage. Subacute and chronic toxicity are associated with changes in the brain and/or the spinal cord which may be progressive and even lead to coma and death in severe cases. It is believed that MTX can induce direct toxic effects to the CNS by damaging the neuronal tissue. Moreover, MTX interferes with the metabolic pathways of folates, excitatory amino acids, homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, adenosine and biopterins, inducing biochemical alterations which have been associated with neurotoxic symptoms. It has been suggested that acute toxicity is partly mediated by adenosine, whereas homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, excitatory amino acids and biopterins may play an important role in the development of subacute and chronic toxicity. A better understanding of the pathogenesis of MTX neurotoxicity would offer the possibility of developing new therapeutic strategies for its treatment or prevention.
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