Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the pattern and degree of hepatic transaminitis experienced by children undergoing autologous transplantation for neuroblastoma. Sixty-four children with high-risk neuroblastoma received an autologous transplant with cyclophosphamide, etoposide, and carboplatin conditioning. Forty-eight went on to receive a second transplant with M and TBI conditioning. Charts were reviewed for evidence of hepatic regimen-related toxicity. A high rate of transaminitis was observed after both regimens. In each transplant, there was an early period of transaminitis during conditioning, from which patients recovered, followed by a second period of transaminase elevation. The degree of elevation was not associated with age, whether the administered dose was calculated based on a per kg or per M(2) basis or the presence of regimen-related severe mucositis. Elevated transaminases at admission were not associated with maximal hepatotoxicity during the first transplant although there was an association in the second transplant. However, the magnitude of transaminase elevation was less in the second transplant. VOD occurred in one and three patients in transplants 1 and 2, respectively. Both conditioning regimens were associated with an early and late elevation of transaminases without significant cholestasis. This biphasic pattern of transaminitis has not been reported previously. The high prevalence of transaminase elevation at time of both transplants was not associated with an increased incidence of VOD. We conclude that elevated transaminases should not preclude proceeding to a first or second autologous transplant with these regimens.
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PMID:A novel pattern of transaminase elevation associated with autologous transplant for neuroblastoma. 1691 89

Pruritus is a frequent symptom in patients with cholestatic liver diseases. Pruritus can be excruciating and, in rare cases, become a primary indication for liver transplantation. The molecular mechanism of itch signal transduction is largely unclear. It was our hypothesis that compounds which accumulate in the circulation during cholestasis act as direct or indirect pruritogens by affecting signaling in itch fibers. To test this, we screened plasma samples of a large group of patients with various cholestatic conditions for their capacity to activate neuroblastoma cells. Quite strikingly, we found that samples from itchy cholestatic patients caused a significantly higher activation than samples from non-itchy cholestatic patients and healthy controls. Purification revealed lysophosphatidic acid (LPA) as the active compound. LPA is a very potent signaling lipid that can activate cells through various LPA receptors. Subsequently, we could demonstrate that cholestatic patients with pruritus have highly elevated levels of serum autotaxin (ATX), the enzyme that converts lysophosphatidylcholine into LPA. This is a striking finding as ATX has never been connected to itch perception thus far. We have also shown that LPA, when injected intradermally, causes itching in mice. On the basis of our results, we hypothesize that during cholestasis, expression of ATX is induced and gives rise to increased local formation of LPA near unmyelinated nerve endings of itch fibers. LPA then activates these neurons through one of the LPA receptors, which in turn potentiates action potentials along itch fibers.
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PMID:The molecular mechanism of cholestatic pruritus. 2169 Nov 8