RESUMEN

OBJECTIVES: To validate a novel intraoperative method of quantifying femoral head perfusion in adult patients with femoral neck fractures and to determine whether the lack of a perfusion waveform correlates with the development of osteonecrosis, nonunion, or reoperation. DESIGN: Prospective cohort. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Nineteen patients with 20 acute femoral neck fractures treated with hip-preserving surgical fixation. All patients underwent intraoperative quantification of femoral head perfusion. INTERVENTION: Intraoperative quantification of femoral head perfusion pressure and waveform utilizing an intracranial pressure monitor. MAIN OUTCOME MEASUREMENTS: Radiographic union, avascular necrosis, revision surgery. RESULTS: Nineteen patients (8 male, 11 female, average age 56 ±â€Š21 years) with 20 femoral neck fractures were enrolled. Eight fractures were stable (Garden 1-2/OTA B1.1-1.3) and 12 were unstable (Garden 3-4/OTAB2.1-3.3). A waveform was present in 12 of 20 cases. The average pressures were systolic 36.8 mm Hg, diastolic 30.8 mm Hg, pulse pressure 6.0 mm Hg. A perfusion waveform was significantly associated with advanced age (P = 0.02) and accompanied by trend toward stable fracture patterns. There were 4 deaths during the 1-year follow-up period (20%), and there were 5 conversions to total hip arthroplasty (25%). There was no significant association between revision surgery or death with the absence of a waveform. CONCLUSIONS: Our study demonstrated the feasibility of a relatively low cost, minimally invasive, technique to quantify femoral head perfusion. In our limited sample, the absence of perfusion did not correlate with our main outcomes; however, the trend toward correlation with increased fracture displacement was as expected. A larger cohort of patients will be needed to detect a significant difference between those with and without a perfusion waveform with regards to our primary outcomes. Further study is needed to delineate the role such data may play in medical decision making at the time of index surgery. LEVEL OF EVIDENCE: Prognostic Level II.

RESUMEN

INTRODUCTION: Femoral head avascular necrosis (AVN) affects between 10% and 41% of children with sickle cell disease (SCD), resulting in the development of proximal femoral deformity and residual hip pain in the majority of patients without treatment. There have been multiple adult studies published on the outcomes of core decompression with and without the use of bone marrow aspirate concentrate (BMAC) injection both in idiopathic and SCD-related AVN with promising results, however, few studies have reported on outcomes in skeletally immature patients. PURPOSE: This study sought to report on a single surgeon's outcomes for core decompression with BMAC injection in pediatric patients with AVN of the femoral head secondary to underlying SCD. METHODS: A single-center, retrospective review was performed for pediatric patients undergoing core decompression with BMAC injection for femoral head AVN in patients with SCD with a minimum of 12-month follow-up. Demographic, radiographic, and clinical variable were collected. Patients were subdivided based upon presence of open femoral physes at the time of surgery. Successful treatment was defined as the ability to return to activities without limitations. RESULTS: A total of 13 patients (average age 14.1±2.8 y, 84.6% male, 6 skeletally immature and 7 skeletally mature) with 18 affected extremities were identified. Open physes were present in 50% of operative extremities. Skeletally immature patient demonstrated reconstitution of the femoral head in 78% of cases and 89% demonstrated regression of at least 1 Steinberg grade and none had progression. Skeletally immature patients were significantly more likely to return to activities (100% vs. 55.6%, P=0.023) and achieve a final Tonnis grade <2 (89% vs. 44%, P=0.046). CONCLUSION: Core decompression appears to alter the natural history of AVN in skeletally immature patients with SCD. Skeletal immaturity was a positive prognostic factor for the ability to return to activities without pain and achieve a lower Tonnis grade at final follow-up.

Asunto(s)

Anemia de Células Falciformes , Necrosis de la Cabeza Femoral , Adolescente , Anemia de Células Falciformes/complicaciones , Médula Ósea/diagnóstico por imagen , Niño , Descompresión , Femenino , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/etiología , Necrosis de la Cabeza Femoral/cirugía , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

In vitro low-dose studies are important to understand the mechanisms of bisphenol A (BPA) action. BPA doses used in current in vitro studies varied considerably, and doses as low as 10(-15)M have been reported. The actual doses of BPA used in the in vitro low-dose studies were rarely checked analytically, and the background BPA levels in experimental materials, which will determine the lowest BPA dose to be used, should be investigated or considered. In this study, the background BPA levels in various materials typically used in in vitro low-dose studies for BPA were investigated. Background BPA levels from the use of disposable pipettes and pipette tips were low (<0.20 ng mL(-1) or 0.88 nM). BPA was also detected in several commercial buffer solutions at levels close to the method limit of quantification (LOQ) (0.02 ng mL(-1); 0.088 nM). However, BPA was detected in all cell culture media obtained from various sources at levels ranging from 0.080 to 4.26 ng mL(-1) (or 0.35 to 19 nM) with an average of 0.83 ng mL(-1) (3.5 nM). We suggest that culture media used for low-dose BPA studies should be analysed for background BPA levels prior to use, and the medium with the lowest BPA levels should be used.

Asunto(s)

Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Fenoles/análisis , Pruebas de Toxicidad , Compuestos de Bencidrilo , Polipropilenos/química , Poliestirenos/química

RESUMEN

Contamination of the environment with endocrine-disrupting chemicals (EDC) has raised concerns about potential health hazards for humans and wildlife. Human and wildlife exposure to one such ubiquitous chemical, p-tert-octylphenol (OP), are likely, due to its persistence in the environment and its presence in food, water, and items of daily use. OP is reported to bind to the estrogen receptor (ER) and alter expression of estrogen-responsive genes. Detrimental effects of OP exposures on the reproductive system have been observed in most, but not all, in vivo experiments. This study examined estrogenic effects of oral exposures of adult female rats to OP. In vitro, OP bound weakly to human ER and a co-activator protein, and accelerated proliferation of MCF-7 cells. Adult Sprague-Dawley rats were given OP by gavage daily for 35 d (25, 50, or 125 mg/kg/d). Body and organ weights and ovarian follicle populations were not significantly altered in OP-exposed adult rats, despite detectable levels of OP in reproductive organs. The estrous cycle of rats was slightly altered, but there were no significant estrogen-like changes in histomorphology or gene expression of the uterus. Prepubertal rats given 125 or 250 mg/kg OP by gavage for 3 d had reduced body weight compared to vehicle-exposed rats but failed to show any uterotrophic response, although 17alpha-ethinyl estradiol (EE, 10 microg/kg/d, ip) induced a threefold increase in uterine weight. Overall, results suggest that toxicity will occur before estrogenic effects with oral exposures to OP. Relevant environmental exposures likely pose little risk for estrogenic effects.

Asunto(s)

Disruptores Endocrinos/toxicidad , Estrógenos no Esteroides/toxicidad , Fenoles/toxicidad , Tensoactivos/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Disruptores Endocrinos/metabolismo , Estradiol/sangre , Estrógenos no Esteroides/metabolismo , Ciclo Estral/efectos de los fármacos , Ciclo Estral/fisiología , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Tamaño de los Órganos/efectos de los fármacos , Fenoles/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Tensoactivos/metabolismo , Pruebas de Toxicidad , Útero/efectos de los fármacos , Útero/patología

RESUMEN

p-tert-Octylphenol (OP) is a degradation product of alkylphenol ethoxylates. OP is an endocrine disruptor known to bind to the estrogen receptor; however, effects on males are controversial. The objective of this study was to evaluate the effects of chronic exposure to OP on male reproduction. Adult Sprague-Dawley rats were administered OP for 60 d, representing 1.5 cycles of spermatogenesis. Experimental groups included a vehicle control, and three doses of OP (25, 50, or 125 mg/kg body weight [bw]) administered daily by gavage. There was a significant decrease in body weight in the 125-mg/kg group after 60 d of treatment. Both testicular and epididymal weights and histology were not altered by treatment with OP at any of the doses administered. There were no marked differences in cauda epididymal sperm counts at any doses; however, total percent sperm motility was significantly lower in rats exposed to the intermediate dose (50 mg/kg bw). There was an increase in percent static sperm cells in all OP-treated groups, with the intermediate dose (50 mg/kg) displaying a significantly higher proportion of static cells relative to untreated controls. Caput epididymal sperm motility was unaltered by OP treatment. Gene expression profiles of testes from control and high-dose-exposed rats indicate that 14 genes were modulated by at least twofold, although these changes were not statistically significant. Taken together, results from this study indicate that OP treatment of adult rats does not appear to exert major effects on male reproductive endpoints at relevant environmental exposure doses.

Asunto(s)

Contaminantes Ambientales/administración & dosificación , Contaminantes Ambientales/toxicidad , Fenoles/administración & dosificación , Fenoles/toxicidad , Espermatogénesis/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Epidídimo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Semen/efectos de los fármacos , Recuento de Espermatozoides , Testículo/efectos de los fármacos

RESUMEN

To investigate possible interactions between the human androgen receptor and PCBs in vitro, we have used a previously characterized human androgen receptor reporter gene assay in which PC-3 LUC(AR+) cells respond to 5alpha-dihydrotestosterone (DHT, 50 pM) with enhanced luciferase activity. The effects of Aroclors, commercial mixtures of PCBs, or polychlorinated terphenyls (PCTs) (0, 0.1, 1.0, and 10.0 microM) on luciferase activity in PC-3 LUC(AR+) cells were determined after exposure for 18 h in the presence and absence of DHT (50 pM). In the absence of DHT, none of the Aroclors induced luciferase activity but, in the presence of DHT (50 pM), Aroclors 1016, 1221, 1232, 1242, 1248, 1254, 1260, 5432, and 5442 acted antagonistically at concentrations that did not affect cell viability. Aroclor 5460 was without effect. Similarly, when PCBs found as human milk contaminants were assessed as individual congeners (each at 1 microM, where no cytotoxic effects were observed), none activated luciferase expression in the absence of DHT but PCBs 49, 66, 74, 105, and 118 completely antagonized the stimulation by DHT (50 pM) and PCBs 138, 153, and 156 were less effective antagonists, reducing the DHT stimulation by about 50%. Thus, 30% (by weight) of the PCBs in human milk are androgen antagonists (PCBs 66, 74, 105, and 118) and a further 25% are partial antagonists (PCBs 138, 153, and 156). A proportionally representative mixture of PCBs that contaminate human milk also caused the DHT-mediated activation of luciferase activity in PC-3 LUC(AR+) cells to be reduced by more than 50%.

Asunto(s)

Antagonistas de Andrógenos/toxicidad , Arocloros/toxicidad , Contaminantes Ambientales/toxicidad , Receptores Androgénicos/metabolismo , Andrógenos , Carcinoma/tratamiento farmacológico , Carcinoma/metabolismo , Carcinoma/patología , Supervivencia Celular/efectos de los fármacos , Dihidrotestosterona/farmacología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Genes Reporteros/genética , Humanos , Luciferasas/antagonistas & inhibidores , Luciferasas/genética , Luciferasas/metabolismo , Masculino , Leche Humana/química , Compuestos de Policloroterfenilo/toxicidad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Transfección , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patología

RESUMEN

The interaction between tris(4-chlorophenyl)methanol (TCPM), an environmental contaminant of uncertain origin, and the human androgen receptor was examined in vitro using a previously characterized human androgen receptor reporter gene assay in which PC-3 LUC(AR+) cells respond to 5alpha-dihydrotestosterone (DHT) with enhanced luciferase activity. In two preliminary studies, TCPM (1 microM) had no effect on androgen receptor activation in the absence of DHT (50 pM), but DHT-mediated activation of the androgen receptor was decreased more than 90% by TCPM at 1 microM. This was not due to an effect of TCPM on cell viability since, with TCPM concentrations of 0.1 and 1.0 microM, cell viability was 111 and 102%, respectively, but at 10 microM TCPM, cell viability was reduced to 60% compared with controls. For kinetic studies of the effects of TCPM on androgen receptor activation, DHT was added at 0, 5, 25, 50, 75, 100, 250 and 500 pM and the TCPM concentrations used were 0, 1, 10, 100, 300 and 1000 nM. This range incorporated the levels of TCPM in human adipose tissue, where concentrations up to 55 nM (20 ng/g lipid) have been measured. TCPM increased the value of the K(m(app)) of the androgen receptor for DHT 4-6-fold with little or no effect on the V(max(app)). Slope and intercept replots revealed that TCPM inhibited the DHT-mediated activation of the androgen receptor in a competitive manner with K(i(app)) values of 0.26, 0.26 and 0.20 microM compared with respective K(m(app)) values of 9.8, 3.1 and 3.9 pM. Thus, TCPM is a competitive antagonist of human androgen receptor activation and the value of the K(i(app)) indicates that TCPM would be approximately 10-50 times more potent as an inhibitor than the previously identified androgen receptor antagonists p,p'-DDE and vinclozilin and also, the K(i(app)) values (200-260 nM) are very close to the concentration of TCPM found in the adipose tissue of some humans (55 nM).

Asunto(s)

Receptores Androgénicos/efectos de los fármacos , Compuestos de Tritilo/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colorantes , Diclorodifenil Dicloroetileno/toxicidad , Contaminantes Ambientales/toxicidad , Humanos , Técnicas In Vitro , Cinética , Masculino , Rojo Neutro , Próstata/metabolismo

RESUMEN

Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.

Asunto(s)

Contaminantes Ocupacionales del Aire/toxicidad , ADN/efectos de los fármacos , Mutágenos , Fenoles/toxicidad , Animales , Compuestos de Bencidrilo , Mutación del Sistema de Lectura , Indicadores y Reactivos/farmacología , Hígado/metabolismo , Masculino , Modelos Químicos , Pruebas de Mutagenicidad , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Salmonella/efectos de los fármacos , Salmonella/genética , Nitrito de Sodio/farmacología