RESUMEN
BACKGROUND: Quetiapine (Seroquel) is a new atypical antipsychotic agent developed for the treatment of schizophrenia. This dibenzothiazepine derivative possesses high affinity for 5-HT2 receptors with lower affinity for D1 and D2 dopamine receptors. In comparison to other antipsychotic agents, quetiapine has less antimuscarinic and alpha1 antagonist receptor activity. Overdose reports outside of clinical trials are limited. We report an intentional overdose of quetiapine by a schizophrenic. CASE REPORT: A 26-year-old female presented to the emergency department following an alleged ingestion of greater than 10,000 mg of quetiapine. At 1 1/2 hours postingestion, the patient was awake, ambulatory, and responded to verbal stimuli. At 2 1/2 hours postingestion, the patient experienced a decreased level of consciousness and responded only to deep pain. Physical findings included sinus tachycardia, pupils 3-4 mm and sluggish, and BP 135/70. Within 16 hours, the patient became awake and alert and was subsequently extubated. Serum electrolytes and blood count were unremarkable. The electrocardiogram at 18 hours postingestion showed a sinus tachycardia, which lasted for approximately 40 hours postingestion. A follow-up electrocardiogram at 42 hours postingestion was normal. CONCLUSION: This ingestion resulted in the loss of consciousness with need for airway protection and persistent tachycardia. Major overdoses of quetiapine warrant close observation in an intensive care setting.
Asunto(s)
Antipsicóticos/envenenamiento , Dibenzotiazepinas/envenenamiento , Inconsciencia/inducido químicamente , Adulto , Antipsicóticos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Dibenzotiazepinas/administración & dosificación , Sobredosis de Droga , Electrocardiografía/efectos de los fármacos , Femenino , Humanos , Pupila/efectos de los fármacos , Fumarato de Quetiapina , Esquizofrenia Paranoide/tratamiento farmacológico , Taquicardia Sinusal/inducido químicamenteRESUMEN
OBJECTIVES: Measurement of the percentage of free prostate-specific antigen (%FPSA) in serum can improve the specificity of prostate cancer screening. We evaluated the ability of %FPSA to predict pathologic features of screen-detected clinically localized prostate cancer. METHODS: We evaluated the correlation between %FPSA in serum before cancer diagnosis and the pathologic features of the cancers detected in 108 men with clinically localized prostate cancer who were treated with radical prostatectomy and for whom complete embedding of the radical prostatectomy specimen was performed. Ninety-seven men (90%) had a previous negative screening evaluation before prostate cancer was detected. RESULTS: There was a negative correlation of %FPSA with penetration of cancer through the prostatic capsule, cancerous surgical margins, Gleason score, percentage of cancer in the gland, and tumor volume (r = -0.2 to -0.4). After controlling for other preoperative predictors, %FPSA predicted capsular penetration (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1 to 2.4, for each 5% decrease in %FPSA) and cancer volume 0.5 cc or greater (adjusted OR 1.6, 95% CI 1.1 to 2.3). Preoperative %FPSA also predicted possibly harmless cancer (OR 1.5, 95% CI 1.1 to 2.2, for each 5% increase in %FPSA). CONCLUSIONS: In a select group of men for whom cancer was detected early via screening, a lower %FPSA in serum suggests a potentially more threatening cancer. This information may aid patients and clinicians in making more informed decisions about the management of prostate cancer, such as selecting patients for watchful waiting. However, more research is needed to determine the performance characteristics of %FPSA in clinical practice.
Asunto(s)
Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico , Anciano , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Canarypox virus, ALVAC, does not replicate in infected mammalian cells and has potential as a vector for gene therapy in the treatment of cancer. PURPOSE: Recombinant viruses carrying DNA sequences encoding interleukin 2 (ALVAC-IL-2), interferon gamma (ALVAC-IFN gamma), tumor necrosis factor-alpha (ALVAC-TNF-alpha), or the co-stimulatory molecule B7-1 (ALVAC-B7-1) were investigated as agents for the treatment of a newly defined mouse prostate tumor model. METHODS: RM-1 mouse prostate cancer cells, which are syngeneic (i.e., same genetic background) to C57BL/6 mice, were used. The expression of foreign gene products in vitro in infected RM-1 cells was measured by immunoprecipitation, bioassay, or flow cytometry. The effects of foreign gene product expression on RM-1 tumor cell growth in C57BL/6 mice were measured after subcutaneous injection (in the back) of 5 x 10(5) uninfected or infected cells; measurements included determinations of time to a measurable tumor size, tumor size as a function of time, and survival. The induction of protective immunity by uninfected and infected RM-1 cells was tested by injection of lethally irradiated (70 Gy) cells and subsequent challenge with uninfected cells. The generation of cytotoxic T cells was monitored by use of a 51Cr release assay. Severe combined immunodeficient (SCID) mice were used to determine whether T or B lymphocytes were involved in ALVAC vector-mediated antitumor responses. Data were analyzed by use of Pearson's modification of the chi-squared test and Kaplan-Meier survival methods. Reported P values are two-sided. RESULTS: The level of foreign gene product expression in ALVAC-infected RM-1 cells was dependent on the multiplicity of virus infection used; a multiplicity of five viruses per infected cell was chosen for subsequent experiments. RM-1 tumor growth in C57BL/6 mice was not affected by tumor cell expression of IL-2 alone, IFN gamma alone, or B7-1 alone; however, expression of TNF-alpha alone significantly delayed tumor growth at early time points (compared with parental ALVAC-infected tumors, P = .0001 at day 21 and P = .037 at day 28). Tumor cell expression of both TNF-alpha and IL-2 completely inhibited tumor growth in 60%-100% of treated mice. No protection against subsequent tumor challenge was detected in mice previously exposed to RM-1 cells expressing both TNF-alpha and IL-2. Cytotoxic T-lymphocyte activity toward RM-1 cells was not observed in C57BL/6 mice that rejected tumors. Tumor cell expression of TNF-alpha and IL-2 also resulted in tumor growth inhibition in SCID mice. CONCLUSIONS: RM-1 mouse prostate cancer cells are readily infected by ALVAC vectors, and foreign gene products are efficiently expressed. Inhibition of RM-1 tumor growth by tumor cell expression of TNF-alpha and IL-2 appears to involve nonspecific antitumor activity.