Update on the treatment of polycythemia vera with recombinant interferon alfa or imatinib mesylate

Polycythemia vera is a myeloproliferative disease, which, if untreated, leads to thrombohemorrhagic complications and eventually to progressive myelofibrosis, anemia, and splenomegaly. Two newly available drugs, interferon alfa and imatinib mesylate, may alter the course of this disease. Used as single agents, each produces lasting remissions in about 75% of patients with polycythemia vera. Of significance, change in JAK2 expression has been reported after treatment with both agents.     

Factors determining the ability of parents to effectively administer intramuscular adrenaline to food allergic children

Intramuscular adrenaline is the treatment of choice for food-related anaphylactic reactions. Although auto-injectable adrenaline devices are routinely prescribed for patients at risk of serious reactions, previous studies have shown that only one-third to one and a half of patients or their carers are able to properly use these devices. The aim of this study was to determine which factors are most strongly associated with the effective use of these devices. A 122 children with food allergies who had previously been prescribed EpiPens and were attending a single specialist pediatric allergy center in the UK. were studied prospectively. A 69% of parents were unable to use the EpiPen, did not have it available, or did not know when it should be administered. A prior practical demonstration was associated with a 4-5 fold greater chance that parents would be able to use the device (p < 0.005). Prior consultation with an allergy specialist rather than a general physician, and parents who independently sought additional information from the national self-help allergy organization were also four to six times more likely to be competent with these devices (p < 0.005). The study clearly shows that for EpiPens to be used safely and effectively it is essential to educate the carer at the time the device is prescribed.     

Foot Polydactyly and Polysyndactyly: Genetic Implications in Two Families

The purpose of this study was to determine the genetic characteristics of foot polydactyly and identify its inheritance pattern by analyzing familial pedigree. Five cases from 2 Korean families were studied: 1 is a family whose members have been affected for 4 generations and the other for 2 generations. Using peripheral blood samples, we performed chromosomal analysis using the banding technique with Giemsa stain and karyotyping. We investigated the shape and structure of 46 chromosomes, looking for translation, deletion, inversion, ring chromosome, and isochromosome abnormalities. All peripheral blood samples demonstrated no chromosomal abnormalities, though the genetic nature of foot polydactyly and a new genetic locus was identified recently by other studies. Familial pedigree analysis suggested that polydactyly was inherited as an autosomal dominant trait in the first family. The mode of inheritance for the second family could not be determined due to an insufficient number of family members. The result of this study brought us to the conclusion that, while genetic factors play a major role in polydactyly, other factors may contribute to its occurrence.     

Changes in CSF neurotransmitters in infantile spasms

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.     

Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2^V617F, the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.