Quantification of 5-FU in skin samples for the development of new delivery systems for topical cancer treatment.

5-Fluorouracil (5-FU) is used for the topical treatment of pre-cancerous skin lesions. However, previous reports focus on 5-FU quantification in plasma samples, failing to provide information about drug quantification in the skin. Therefore, the aim of this work was to develop a simple and reliable analytical method employing HPLC-UV for 5-FU quantification in skin samples. Chromatographic separation was obtained using the commonly available Lichrospher RP-C18 endcapped column. Porcine ear skin matrix-based analytical curves with thymine, as internal standard, were used. 5-FU was eluted at 5.2 min and thymine at 13.0 min. The method was selective, precise and accurate in the linear range from 0.3 to 6 µg/mL. The samples were stable after three cycles of freeze/thawing and extraction efficiency rates above 95% were obtained. In vitro skin penetration studies of an aqueous solution and a commercial cream of 5-FU were performed. The cream improved 5-FU retention into the skin and permeation through the skin compared to the solution. Therefore, the method developed herein can be applied to the study of formulations for topical delivery of 5-FU.

Liquid Crystalline Nanodispersions Functionalized with Cell-Penetrating Peptides for Topical Delivery of Short-Interfering RNAs: A Proposal for Silencing a Pro-Inflammatory Cytokine in Cutaneous Diseases.

Short-interfering RNAs (siRNAs) are a potential strategy for the treatment of cutaneous diseases. In this context, liquid crystalline nanoparticles functionalized with specific proteins and peptide-transduction domains (PTDs), which act as penetration enhancers, are a promising carrier for siRNA delivery through the skin. Herein, hexagonal phase liquid crystal nanoparticles based on monoolein (MO) and/or oleic acid (OA) containing (or lacking) the cationic polymer polyethylenimine (PEI) and the cationic lipid oleylamine (OAM) were functionalized with the membrane transduction peptides transcriptional activator (TAT) or penetratin (PNT). These nanoparticles were complexed with siRNA and characterized by particle size, polydispersity, zeta potential, complexation efficiency and siRNA release. The formulations containing cationic agents presented positive zeta potentials, sizes on the nanometer scale, and complexed siRNAs at concentrations of 10 µM; these agents were successfully released in a heparin competition assay. Cell culture studies demonstrated that nanoparticles composed of MO:OA:PEI functionalized with TAT were the most efficient at transfecting L929 cells, and the uptake efficiency was enhanced by TAT peptide functionalization. Thereafter, the selected formulations were evaluated for in vivo skin irritation, penetration and in vivo efficacy using a chemically induced inflammatory animal model. These nanoparticles did not irritate the skin and provided higher siRNA penetration and delivery into the skin than control formulations. Additionally, efficacy studies in the animal model showed that the association of TAT with the nanodispersion provided higher suppression of tumor necrosis factor (TNF)-α. Thus, the development of liquid crystalline nanodispersions containing TAT may lead to improved topical siRNA delivery for the treatment of inflammatory skin diseases.

Droperidol versus haloperidol for chemical restraint of agitated and combative patients.

STUDY OBJECTIVE: To compare two related pharmacological agents used for the chemical restraint of agitated and combative patients. DESIGN AND SETTING: A randomized, double-blind, prospective study was carried out in patients requiring physical restraint in a university hospital emergency department. PARTICIPANTS: Sixty-eight violent or agitated adult patients whom the attending physician believed would benefit from chemical restraint to protect the patient and staff and to expedite evaluation. INTERVENTION: Twenty-one participants were administered 5 mg haloperidol IM; 26 were administered 5 mg droperidol IM; 12 were administered haloperidol IV; and nine were administered 5 mg droperidol IV. RESULTS: All patients were rated on a five-point combativeness scale at five, ten, 15, 30, and 60 minutes after the study drug was given. Vital signs also were recorded at these times. IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route (beta at the 5% confidence level, P = .78). CONCLUSION: In equal IM doses (5 mg), droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.

Axillosubclavian vein thrombosis: case report.

Deep-vein thrombosis of the upper extremity, that is, axillosubclavian vein thrombosis, is a relatively rare and potentially overlooked diagnosis in the emergency department (ED). It can be the cause of significant morbidity and it may be life-threatening. Reported here is the case of a 23-year-old man who presented to the ED with left upper extremity pain and swelling. Venography confirmed the diagnosis of axillosubclavian vein thrombosis. Hospitalization and treatment with intravenous heparin led to a satisfactory recovery. The clinical presentation, predisposing factors, diagnosis, treatment, and complications of this rare entity are discussed.

Effect of premedication on arterial oxygen saturation in children with congenital heart disease.

The effect of a standardized intramuscular premedication (morphine, 0.1 mg/kg, scopolamine, 13 micrograms/kg, and secobarbital, 2.5 mg/kg) on the arterial oxygen saturation of hemoglobin was evaluated in 33 patients with congenital heart disease by use of the Nellcor pulse oximeter. Sixteen patients had noncyanotic congenital heart disease and 17 patients had cyanotic congenital heart disease. In the noncyanotic congenital heart disease group, pulse oximeter saturations decreased from 98.1% +/- 1.5% (mean +/- SD), before premedication, to 96.5% +/- 1.5% following premedication. Although this decrease was statistically significant (P less than 0.05), it was determined to not be clinically meaningful. In the patients with cyanotic congenital heart disease, oxygen saturation increased from 73.5% +/- 11.8 to 74.7% +/- 10.2 following premedication, but this change was not statistically significant. The effect of premedication on SaO2 was highly variable in patients with cyanotic heart disease; although the group mean appeared to increase, 6 of the 17 patients had decreases in saturation and the decrease exceeded 10% in saturation in 3 of them. Therefore, oxygen saturation should be monitored following premedication in patients with cyanotic heart disease and oxygen administered as needed.

Acute occlusion of the left renal artery manifested by hypertensive crisis.

Because the signs and symptoms of acute renal artery occlusion mimic those of many more common diseases, prompt diagnosis is aided by an awareness that an occlusive renovascular event may have occurred. No routine, noninvasive laboratory test can confirm the diagnosis. Renal arteriography is the procedure of choice after excretory urograms have ruled out an obstructive uropathy. Early assessment of kidney viability is important. The endpoints of emergency treatment are to decrease symptoms, decrease diastolic blood pressure to less than or equal to 105 mm Hg, and to maintain urine output at greater than 50 mL/h. Restoration of a lower blood pressure must not be so prompt that renal perfusion decreases too rapidly. Definitive surgical treatment versus medical management of the renal artery occlusion remains a controversial topic. Where surgery is not feasible, medical management consists of streptokinase acutely followed by heparin and then chronic coumarin therapy.

Immunogenicity of a yeast-derived hepatitis B vaccine (Engerix-B) in healthy young adults.

In a study comparing the safety and immunogenicity of a recombinant DNA yeast-derived hepatitis B vaccine with that of a plasma-derived vaccine in young female adults, 50 subjects were vaccinated with the former and 29 with the latter vaccine according to a 0, 1, and 6 month vaccination schedule. Results indicated that the yeast-derived vaccine was safe and highly immunogenic. Two months after the second vaccine dose, 86% of subjects seroconverted, a rate which increased to 100%, 30 days after the booster dose. Moreover, anti-HBs geometric mean titres increased progressively after the first two doses and rose markedly to 1098 IU/l after the booster dose. Although similar rates of seroconversion were obtained with both vaccines, the anti-HBs GMT of the plasma-derived vaccine was higher (P less than 0.05) than that elicited by the yeast-derived vaccine.