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San Antonio, TX, United States

Roy S.L.,Centers for Disease Control and Prevention | Atkins J.T.,Methodist Childrens Hospital | Gennuso R.,Methodist Childrens Hospital | Kofos D.,Methodist Childrens Hospital | And 8 more authors.
Parasitology Research | Year: 2015

Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities. © 2015, Springer-Verlag Berlin Heidelberg (outside the USA). Source


Winter H.S.,MassGeneral Hospital for Children | Krzeski P.,Medpace | Heyman M.B.,University of California at San Francisco | Ibarguen-Secchia E.,Methodist Childrens Hospital | And 9 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Objective: The aim of the study was to assess the safety and efficacy of highand low-dose oral, delayed-release mesalamine in a randomized, doubleblind, active control study of children with mild-to-moderately active ulcerative colitis.Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥10 to ≤55 and a truncated Mayo Score of ≥1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g-1 · day-1) or highdose group (53-118 mg · g-1 · day-1). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥10 with a decrease from baseline by ≥20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity.Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P=0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups.Conclusions: Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose. Copyright © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Source

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