Anesthetic and Surgical Management of a Bilateral Mandible Fracture in a Patient With Charcot-Marie-Tooth Disease: A Case Report.

PURPOSE: This report describes the case of a 74-year-old man who had been diagnosed with Charcot-Marie-Tooth disease as a child. Because the patient had serious motor and sensory neuropathy associated with his disease, special anesthetic and surgical recommendations had to be considered before he underwent general anesthesia to repair his mandibular fracture. MATERIALS AND METHODS: Repair of the mandible was performed under general anesthesia with a nasal endotracheal tube and the use of the nondepolarizing muscle relaxant rocuronium. Open reduction and internal fixation through extraoral approaches were used to fixate the displaced right subcondylar and symphyseal fractures. A closed reduction approach using maxillary fixation screws and a mandibular arch bar with light elastic guidance was used to treat a nondisplaced fracture of the left mandibular ramus. Rigid fixation allowed for avoidance of a period of intermaxillary fixation. RESULTS: General anesthesia and muscle relaxant were administered without complication. Treatment of bilateral mandibular fractures with combined open and closed approaches resulted in restoration of premorbid occlusion and masticatory function. CONCLUSION: Repair of mandibular fractures under general anesthesia appears to be a safe procedure in patients with Charcot-Marie-Tooth disease when appropriate anesthetic and surgical methods are used.

Management of tooth extraction in a patient with a rare bleeding disorder associated with Hermansky-Pudlak syndrome: a case report.

PURPOSE: This report describes the case of a 27-year-old man who had been diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient had a major bleeding disorder associated with his syndrome, local and systemic hemostatic protection recommendations had to be considered before tooth extraction. MATERIALS AND METHODS: Synthetic vasopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to the extraction site. RESULTS: Treatment with DDAVP, HLA-matched platelets, and local application of a packing with Avitene and Gelfoam resulted in sustained hemostasis and an excellent healing response. CONCLUSION: Surgical and routine extractions appear to be safe procedures in patients with Hermansky-Pudlak syndrome when appropriate local and systemic hemostatic measures are used.

Quantification of sunitinib in human plasma by high-performance liquid chromatography-tandem mass spectrometry.

A rapid, sensitive and specific method was developed and validated using LC/MS/MS for determination of sunitinib in human plasma. Sample preparation involved a liquid-liquid extraction by the addition of 0.2mL of plasma with 4.0mL tert-butyl-methyl-ether extraction solution containing 25ng/mL of the internal standard clozapine. Separation of compounds was achieved on a C18 (50mmx2.1mm i.d., 3.5microm) analytical column using a mobile phase consisting of acetonitrile/H20 (65:35, v/v) containing 0.1% formic acid and isocratic flow at 0.150mL/min for 3min. The analytes were monitored by tandem-mass spectrometry with electrospray positive ionization. Linear calibration curves in human plasma were generated over the range of 0.2-500ng/mL with values for the coefficient of determination of >0.9950. Within- and between day precision and accuracy were < or =10%. The method was applied to the quantitation of sunitinib in plasma samples from a patient receiving daily oral therapy with sunitinib.

Stability of sunitinib in oral suspension.

BACKGROUND: Sunitinib is a novel, oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. No liquid formulation of sunitinib malate is commercially available for pediatric administration. OBJECTIVE: To prepare extemporaneously an oral liquid formulation of sunitinib malate from commercially available capsules and study its chemical and physical stability in suspension at room temperature and under refrigeration at 4 degrees C. METHODS: Six independent samples were prepared by mixing the contents of 3 sunitinib malate capsules (each equivalent to 50 mg of sunitinib) with 15 mL of a 1:1 mixture of Ora-Plus:Ora-Sweet solution to yield a final concentration of 10 mg/mL. Suspensions were stored in amber plastic bottles with child-resistant caps. Three samples were refrigerated at 4 degrees C and 3 were stored at room temperature. Aliquots from each bottle were obtained on days 1, 2, 3, 5, 7, 14, 21, 30, and 60 and diluted to a final concentration of 300 ng/mL with 500 ng/mL of clozapine in 50% acetonitrile. Sunitinib concentrations were then measured by a liquid chromatography-tandem mass spectrometry assay validated in our laboratory. RESULTS: At room temperature and under refrigeration at 4 degrees C, sunitinib in a 10-mg/mL suspension of sunitinib malate with Ora-Plus:Ora-Sweet 1:1 maintained greater than 96% of its initial concentration for 60 days. Visual appearance (color and consistency) and odor of drug suspension remained unchanged during the study. CONCLUSIONS: Sunitinib is stable in an oral suspension prepared from commercially available capsules for at least 60 days at room temperature and refrigeration at 4 degrees C. This liquid formulation is better suited for administration to children and adults with cancer who cannot swallow sunitinib capsules.

Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia.

We compared the antitumor activities of the multitargeted tyrosine kinase inhibitors imatinib, sorafenib, and sunitinib to determine which inhibitor is best suited to be used for the treatment of acute myelogenous leukemia (AML). In nine human AML cell lines, sorafenib and sunitinib were more potent inhibitors of cellular proliferation than imatinib (IC50, 0.27 to >40, 0.002-9.1, and 0.007-13 micromol/L for imatinib, sorafenib, and sunitinib, respectively). Sorafenib and sunitinib were potent inhibitors of cells with fms-like tyrosine kinase 3 internal tandem duplication (IC50, 2 and 7 nmol/L) and c-KIT N822K mutations (IC50, 23 and 40 nmol/L). In four cell lines (MV4-11, Kasumi-1, KG-1, and U937) that spanned a range of drug sensitivities, sorafenib and sunitinib had similar activity in apoptosis and cell cycle assays, except that sunitinib did not promote apoptosis in U937 cells. Both drugs inhibited mitogen-activated protein kinase signaling but had no effect on AKT signaling in most of the cell lines tested. Sorafenib was substantially more bound than sunitinib in human plasma (unbound fraction, 0.59% versus 8.4%) and cell culture medium (unbound fraction, 1.3% versus 39%), indicating that sorafenib was more potent than sunitinib and that unbound sorafenib concentrations with activity against most AML cell lines are achievable in vivo. There was more intracellular accumulation of sorafenib than of sunitinib and imatinib in AML cells. Between 1 and 10 micromol/L, sorafenib inhibited the proliferation of six of nine primary AML blast samples by > or =50%. Our results highlight the pharmacologic features of sorafenib that may provide it an advantage in the treatment of AML.

Determination of Cloretazine (VNP40101M) and its active metabolite (VNP4090CE) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS).

A sensitive method for the determination of Cloretazine (VNP40101M) and its metabolite (VNP4090CE) with an internal standard (ISTD) in human plasma was developed using high-performance liquid chromatographic separation with tandem mass spectrometric detection. Acidified plasma samples (500 microL) were prepared using solid phase extraction (SPE) columns, and 25 microL of the reconstituted sample was injected onto an Ascentis C18 HPLC column (3 microm, 5 cmx2.1 mm) with an isocratic mobile phase. Analytes were detected with an API-3000 LC-MS/MS System at unit (Q1) and low (Q3) resolution in negative multiple reaction monitoring mode: m/z 249.0 (precursor ion) to m/z 114.9 (product ion) for both Cloretazine (at 3.64 min) and VNP4090CE (at 2.91 min), and m/z 253.0 (precursor ion) to m/z 116.9 (product ion) for the ISTD. The mean recovery for Cloretazine (VNP40101M) and its metabolite (VNP4090CE) was greater than 87% with a lower limit of quantification of 1.0 ng/mL for Cloretazine (S/N=9.7, CV