Congenital methemoglobinemia type II in a 5-year-old boy.

Congenital Methemoglobinemia is a rare neurologic condition which can mimic other diseases such as epilepsy syndromes and leukodystrophies. The responsible gene, CYB5R3, is not typically included on commonly order neurologic and epilepsy panels. We recommend that laboratories include this gene on these tests which often precede larger-scale genetic studies.

Novel use of dexmedetomidine for the treatment of anticholinergic toxidrome.

INTRODUCTION: We report the case of an adolescent with anticholinergic toxidrome from diphenhydramine overdose, whose symptoms were treated with a novel application of dexmedetomidine. CASE REPORT: A 13-year-old female developed an anticholinergic toxidrome after intentionally ingesting 9.5 mg/kg of diphenhydramine. Despite routine supportive therapies, to include appropriate doses of lorazepam, she continued to have significant agitation, psychosis, and hallucinations. A dexmedetomidine infusion was started to aid in the treatment of her agitation and psychosis with marked improvement of her symptoms. DISCUSSION: Using dexmedetomidine for the treatment of anticholinergic toxidrome has not been previously described in the literature, but there are multiple reports of its use in alcohol withdrawal syndrome. We suggest that adding dexmedetomidine as an adjunctive agent in the therapy of anticholinergic toxidrome may relieve the symptoms of agitation, psychosis, tachycardia, and hypertension, without the attendant risk of respiratory depression associated with high doses of benzodiazepines.

The morbidity and mortality of patients with fungal infections before and during extracorporeal membrane oxygenation support.

OBJECTIVE: To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. DESIGN: Retrospective cohort study. PATIENT AND METHODS: The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. RESULTS: From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. CONCLUSIONS: Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.

Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults.

PURPOSE: The fluoropyrimidine carbamate (capecitabine) is converted to 5-fluorouracil (5-FU) by thymidine phosphorylase (TP) inside target tissues. 5-FU interferes with DNA synthesis by blocking thymidylate synthase (TS) but is inactivated by dihydropyrimidine dehydrogenase (DPD). Favorable enzyme profiles (high TP and low DPD) generate high intratumor levels of 5-FU that are effective against many tumors, especially those with low TS. Capecitabine has not been tested against thyroid cancers, and it is not known to what extent thyroid cancers express TP, TS or DPD. METHODS: To test this, we determined TP, TS and DPD in 19 thyroid cancers from young patients (14 papillary, 4 follicular, 1 medullary) by immunohistochemistry. After approval by the Human Use Committee, the intensity of TP, TS, and DPD staining was determined by two independent examiners and graded (absent=0 to intense=3) with >90% concordance. RESULTS: TS was detected in 7/19 cancers (37%), TP in 14/19 cancers (74%) and DPD in 14/19 cancers (74%). In six tumors, TP was more intense that DPD, suggesting capecitabine sensitivity. Only five tumors failed to express TP but four of these expressed DPD, suggesting capecitabine resistance. Overall, 6/19 tumors (32% of the total) had a favorable expression profile, and all of them were papillary cancers. CONCLUSIONS: We conclude that the majority of differentiated thyroid cancers (74%) express TP and low levels of TS (63% undetectable). The results support the hypothesis that capecitabine is activated in the majority of differentiated thyroid cancers and that 32% have favorable expression of all three enzymes (TP, TS, and DPD).