Because of the severity of some of the infections, such as the risk of meningitis with Coccidioides exposure, strong consideration should be given to antifungal prophylaxis for those at heightened ...risk. Meningitis (Cryptococcus) Ketoconazole (ND; Histoplasma); amphotericin B (ND), fluconazole (ND; Cryptococcus) Lobectomy for Histoplasma-related bronchiectasis Cr1 18/M/A R423Q (DNA binding) Cryptococcus gattii C gattii C gattii meningitis Liposomal amphotericin B, flucytosine, voriconazole Papilledema and increased opening pressures without vision changes Cr2E7 29/F/B ND Cryptococcus neoformans N Colon, perirectal abscess Amphotericin B (10 wk) and 5-flucytosine (ND) ND Cr3E8 31/M/W ND C neoformans N Esophageal Amphotericin B (6 wk) and 5-flucytosine (6 wk) ND Cr4E9 13/M/ND ND C neoformans N Meningitis Amphotericin B (10 wk), 5-flucytosine (6 wk), dexamethasone (12 wk), fluconazole (6 mo) Myeloperitoneal shunt Co1 4/F/W V713M (transactivation) Coccidioides immitis Y Meningitis Liposomal amphotericin, fluconazole Stroke, hydrocephalus, bilateral VP shunt, hypercalcemia Co2E10 17/F/ND T412S (DNA binding) C immitis Y Meningitis, cerebral abscess Amphotericin B (3 wk), fluconazole (lifelong) Altered mental status requiring temporary intubation Co3E11 4/F/ND ND Cimmitis N Meningitis Amphotericin B (ND), fluconazole (ND) Strokes Table E1 Cases and literature review of patients with HIES with endemic fungal infections A, Asian; B, black; N, no; ND, not documented; W, white; Y, yes.
Rationale Dominant negative mutations in STAT3 lead to elevated serum IgE, eczema, and recurrent skin and lung infections, known as autosomal dominant Hyper IgE Syndrome (AD-HIES).
Summary
Background
Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for ...prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours.
Methods
Sixty infants (age 1‐12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used.
Results
One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40‐50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg).
Conclusion
A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.
The objective of the present study was to examine the effect of antenatal or postnatal treatment with corticosteroids on the NMDA receptor, one of the mediators of both normal brain development and ...hypoxic-ischemic injury, by determining the characteristics of the receptor MK-801 binding site in untreated and corticosteroid-treated fetal and newborn lambs. (3)H-MK-801 binding was performed in cerebral cortical cell membranes from fetal sheep at 88, 120, and 136 d gestation (term = 150 d), and from 5-d-old lambs and adult ewes. Animals were randomized to receive dexamethasone fetuses: 6 mg, i.m. every 12 hr for four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.25 mg/kg (high dose) every 12 hr for four doses or placebo. During development, B(max) (apparent number of receptors) increased, reaching a maximum in 5-d-old lambs (p < 0.05) and decreasing in the adult brain. K(d) (dissociation constant) did not change, suggesting that receptor affinity was not altered during maturation. Dexamethasone treatment had no effect on MK-801 binding in the fetus or adult, but in lambs was associated with a significant decrease in B(max) from 2.17 +/- 0.18 pmol/mg protein in placebo-treated animals to 1.65 +/- 0.8 and 1.62 +/- 0.07 pmol/mg protein in low-dose and high-dose animals, respectively. Affinity for (3)H-MK-801 decreased 20% after dexamethasone treatment in lambs only (p < 0.05). Thus, dexamethasone treatment appears to modify the NMDA receptor only during a specific period of brain development.
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