RESUMEN
Based on theoretical frameworks of scientist stereotypes, possible selves, and science identity, written assignments were developed to teach science content through biographies and research of counter-stereotypical scientists-Scientist Spotlights (www.scientistspotlights.org). Previous studies on Scientist Spotlight assignments showed significant shifts in how college-level biology students relate to and describe scientists and in their performance in biology courses. However, the outcomes of Scientist Spotlight assignments in secondary schools were yet to be explored. In collaboration with 18 science teachers from 12 schools, this study assessed the impacts of Scientist Spotlight assignments for secondary school students. We used published assessment tools: Relatability prompt; Stereotypes prompt; and Performance/Competence, Interest, and Recognition (PCIR) instrument. Statistical analyses compared students' responses before and after receiving at least three Scientist Spotlight assignments. We observed significant shifts in students' relatability to and descriptions of scientists as well as other science identity measures. Importantly, disaggregating classes by implementation strategies revealed that students' relatability shifts were significant for teachers reporting in-class discussions and not significant for teachers reporting no discussions. Our findings raise questions about contextual and pedagogical influences shaping student outcomes with Scientist Spotlight assignments, like how noncontent Instructor Talk might foster student shifts in aspects of science identity.
Asunto(s)
Ciencia , Estudiantes , Humanos , Instituciones Académicas , Escritura , Ciencia/educación , Proyectos de InvestigaciónRESUMEN
A primary human skeletal muscle culture (HSMC) system, which retains cellular integrity and insulin responsiveness for glucose transport was employed to evaluate glucose transport regulation. As previously reported, cells cultured from non-insulin-dependent diabetic (NIDDM) subjects displayed significant reductions in both basal and acute insulin-stimulated transport compared to nondiabetic controls (NC). Fusion/differentiation of NC and NIDDM HSMC in elevated media insulin (from 22 pM to 30 microM) resulted in increased basal transport activities but reduced insulin-stimulated transport, so that cells were no longer insulin responsive. After fusion under hyperinsulinemic conditions, GLUT1 protein expression was elevated in both groups while GLUT4 protein level was unaltered. Fusion of HSMC under hyperglycemic conditions (10 and 20 mM) decreased glucose transport in NC cells only when combined with hyperinsulinemia. Hyperglycemia alone down-regulated transport in HSMC of NIDDM, while the combination of hyperglycemia and hyperinsulinemia had greater effects. In summary: (a) insulin resistance of glucose transport can be induced in HSMC of both NC and NIDDM by hyperinsulinemia and is accompanied by unaltered GLUT4 but increased GLUT1 levels; and (b) HSMC from NIDDM subjects demonstrate an increased sensitivity to impairment of glucose transport by hyperglycemia. These results indicate that insulin resistance in skeletal muscle can be acquired in NC and NIDDM from hyperinsulinemia alone but that NIDDM is uniquely sensitive to the additional influence of hyperglycemia.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Insulina/farmacología , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculo Esquelético/metabolismo , Adulto , Biopsia , Diferenciación Celular , Fusión Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 4 , Humanos , Hiperglucemia/metabolismo , Hiperinsulinismo , Persona de Mediana Edad , Proteínas de Transporte de Monosacáridos/efectos de los fármacos , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Valores de ReferenciaRESUMEN
Myoblasts from human skeletal muscle were isolated from needle biopsy samples of vastus lateralis and fused to differentiated multinucleated myotubes. Specific high-affinity insulin and insulin-like growth factor I (IGF-I) binding, glucose transporter proteins GLUT1 and GLUT4, glycogen synthase and pyruvate dehydrogenase proteins, and their specific mRNAs were identified in fused myotubes. Insulin and IGF-I stimulated 2-deoxyglucose uptake twofold with half-maximal stimulation by insulin at 0.98 +/- 0.12 nmol/l and maximal stimulation at 17.5 nmol/l. Acute insulin treatment (33 nmol/l) doubled glycogen synthase activity and glucose incorporation into glycogen while increasing pyruvate dehydrogenase approximately 30%. In cells cultured from NIDDM subjects, both basal (6.9 +/- 1.0 vs. 13.0 +/- 1.7 pmol.mg protein-1.min-1) and acute insulin-stimulated transport (13.5 +/- 2.0 vs. 22.4 +/- 1.3 pmol.mg protein-1.min-1) were significantly reduced compared with nondiabetic control subjects (both P < or = 0.005). GLUT1 protein content of total membranes from NIDDM subjects was decreased compared with control subjects, while GLUT4 levels were similar between groups. A significant correlation (r = 0.65, P < or = 0.05) was present when maximal rates of insulin-stimulated glucose transport in cell culture from subjects were compared with their corresponding in vivo glucose disposal determined by hyperinsulinemic glucose clamp. In summary, differentiated human skeletal muscle cultures exhibit biochemical and molecular features of insulin-stimulated glucose transport and intracellular enzyme activity comparable with the in vivo situation. Defective insulin-stimulated glucose transport persists in muscle cultures from NIDDM subjects and resembles the reduced insulin-mediated glucose uptake present in vivo. We conclude that this technique provides a relevant cellular model to study insulin action and glucose metabolism in normal subjects and determine the mechanisms of insulin resistance in NIDDM.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Insulina/metabolismo , Músculo Esquelético/metabolismo , Adulto , Transporte Biológico/efectos de los fármacos , Biopsia con Aguja , Fusión Celular , Células Cultivadas , Creatina Quinasa/metabolismo , Desoxiglucosa/metabolismo , Glucógeno/biosíntesis , Glucógeno Sintasa/metabolismo , Glucólisis , Humanos , Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Complejo Piruvato Deshidrogenasa/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo , Valores de ReferenciaRESUMEN
To determine whether defects of muscle glycogen synthase (GS) activity can be acquired by exposure to elevated glucose or insulin levels, human skeletal muscle cells obtained by needle biopsy from normal control subjects were grown in culture for 4-6 weeks followed by 4 days of fusion and differentiation in media containing either normal (5.5 mmol/l glucose and 22 pmol/l insulin) or increased concentrations of glucose (20 mmol/l), insulin (30 micromol/l), or both. After fusion in normal media, acute stimulation by 33 nmol/l insulin for 1 h increased GS fractional velocity (FV) approximately twofold (from 9.01 +/- 1.26 to 16.31 +/- 2.40, P < 0.05). Increasing the media glucose concentration alone to 20 mmol/l during fusion had no effect on basal FV but caused a marginal impairment of the insulin-stimulated GS response (from 8.51 +/- 1.33 to 12.99 +/- 1.90, P = 0.08). Increasing the media insulin concentration to 30 micromol/l during fusion at 5.5 mmol/l glucose also did not alter basal GS FV (10.61 +/- 1.69%) but completely abolished the normal insulin-stimulated increase in GS activity (to 11.63 +/- 1.55%, NS). The combination of high insulin (30 micromol/l) and high glucose (20 mmol/l) during fusion had no greater effect on the FV of either basal (11.66 +/- 2.16%, NS) or insulin-stimulated (9.20 +/- 1.80%, NS) GS activity than high insulin alone. Fusion in hyperinsulinemic media altered the kinetic parameters of GS with a near doubling of the basal Km0.1 and Vmax0.1 for uridinediphospho-glucose. Hyperinsulinemia also totally prevented the normal insulin-stimulated threefold increase in the Vmax0.1 and the 65% decrease in the A0.5 for glucose-6-phosphate. GS mRNA and protein expression, determined by RNase protection assay and immunoblotting, respectively, were unaffected by changes in media conditions. We conclude that exposure of human skeletal muscle cells primarily to high insulin induces severe insulin resistance through multiple acquired posttranslational defects, which affect both the kinetic characteristics and absolute activity of the GS enzyme.
Asunto(s)
Glucosa/farmacología , Glucógeno Sintasa/metabolismo , Glucógeno/metabolismo , Insulina/farmacología , Músculo Esquelético/metabolismo , Receptor de Insulina/metabolismo , Actinas/metabolismo , Adulto , Diferenciación Celular , Fusión Celular , Células Cultivadas , Creatina Quinasa/biosíntesis , Creatina Quinasa/metabolismo , Técnicas de Cultivo/métodos , Expresión Génica , Glucógeno Sintasa/biosíntesis , Humanos , Isoenzimas , Cinética , Análisis de los Mínimos Cuadrados , Masculino , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Sondas ARN , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Valores de Referencia , Sarcómeros/metabolismo , Uridina Difosfato Glucosa/metabolismoRESUMEN
Platelet monoamine oxidase (MAO) activity was determined with tryptamine as substrate for 61 drug-free patients who had a primary major depressive disorder and for 32 normal controls. Although there were no significant differences between the mean platelet MAO activity of 19 bipolar patients (4.94 nmoles/hr/mg of protein), 42 unipolar patients (4.97 nmoles), and the controls (4.78 nmoles), an analysis of variance indicated that the variance of the bipolar group was significantly greater than that of the other groups. This suggests that there may be subgroups of bipolar patients that differ in their platelet MAO activity but that appear to be distinct from the bipolar I vs bipolar II classification.
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Plaquetas/enzimología , Depresión/enzimología , Monoaminooxidasa/sangre , Adulto , Trastorno Bipolar/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
We conducted a retrospective study to correlate thrombotic variables with the risk from an acute coronary event, using a new in vitro technique, which measures haemostasis, thrombolysis and coagulation from non-anticoagulated blood samples. The analysis was based on data from 63 patients who had undergone exercise radionuclide ventriculography, 50 of whom were considered to be at risk from an acute coronary event because they satisfied at least one of the following three criteria: (1) coronary angiography documented disease, (2) prior myocardial infarction, (3) ventriculography assessed provocable ischaemia. Fifty matched normal subjects were used as controls. Significantly enhanced haemostasis was measured in patients considered at risk from acute coronary event, and haemostatic activity was further increased in patients with provocable ischaemia. Haemostasis in eight patients at risk (provocable ischaemia), who continued with the medication during the test, did not differ significantly from the controls. Greatly reduced spontaneous thrombolytic activity was measured in all patients at risk from acute coronary events. These findings suggest the presence of hyperactive platelets in patients at risk from acute coronary events, with an additional risk of greatly reduced spontaneous thrombolytic activity.
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Pruebas de Coagulación Sanguínea , Plaquetas/fisiología , Enfermedad Coronaria/sangre , Fibrinólisis , Infarto del Miocardio/sangre , Pruebas de Función Plaquetaria , Adulto , Anciano , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea/instrumentación , Femenino , Hemostasis , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Pruebas de Función Plaquetaria/instrumentación , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Androstenedione infusion to pregnant monkeys leads to premature labor and live delivery. Androstenedione-induced labor also increased placental CRH messenger RNA and peptide to concentrations observed at term in pregnant monkeys. Placental CRH may modulate fetal pituitary-adrenal function during pregnancy in primates. This study tested the hypothesis that androstenedione-induced premature delivery in pregnant monkeys results from androstenedione-induced increases in placental CRH, which stimulate premature activation of the fetal pituitary-adrenal axis. The hypothesis was tested by comparing fetal umbilical vein (FUV) plasma CRH, ACTH, dehydroepiandrosterone sulfate, and cortisol concentrations at cesarean section in fetuses from mothers undergoing spontaneous, term labor (group I), with those in fetuses from mothers undergoing androstenedione-induced, premature labor (group II) and with those from mothers not in labor (group III). In addition, gestation-related changes in maternal plasma CRH concentrations were investigated, and CRH immunoactivity was characterized by Sephadex G50 chromatography in pooled maternal plasma extracts. FUV CRH concentrations were similarly elevated in group I and group II fetuses, compared with group III fetuses. Despite similar FUV blood gases in all fetuses, FUV ACTH and dehydroepiandrosterone sulfate concentrations were higher in group I fetuses than in group II or group III fetuses. The majority of CRH immunoactivity coeluted with synthetic human CRH. Maternal plasma CRH concentrations showed a modest increase with gestation in the rhesus monkey. These data: 1) demonstrate that androstenedione treatment of pregnant monkeys at 0.8 of gestation elevates fetal plasma CRH to similar concentrations measured at term; 2) do not support the hypothesis that androstenedione-induced delivery in the monkey results from premature activation of the fetal pituitary-adrenal axis by placental CRH; but 3) do support a role for activation of the fetal hypothalamo-pituitary-adrenal axis in association with spontaneous term labor in the monkey; and 4) demonstrate important interprimate species differences in maternal CRH physiology.
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Androstenodiona/farmacología , Hormona Liberadora de Corticotropina/sangre , Sangre Fetal , Sistema Hipotálamo-Hipofisario/fisiología , Trabajo de Parto Inducido , Trabajo de Parto/sangre , Macaca mulatta/sangre , Sistema Hipófiso-Suprarrenal/fisiología , Animales , Femenino , Sangre Fetal/metabolismo , Hormonas/sangre , Concentración Osmolar , Embarazo , Venas UmbilicalesRESUMEN
PURPOSE: Rabbits are used commonly for the evaluation of drugs and surgery to lower intraocular pressure (IOP). The authors compared the accuracy and variability of three tonometers for measuring IOP in rabbits. METHODS: The anterior chamber of adult rabbits was cannulated with a 25-gauge needle connected to an elevated bottle of balanced salt solution. The bottle was raised and lowered to control IOP. A fluid-filled pressure transducer also was placed in the anterior chamber. Intraocular pressure was decreased in increments of 5 to 10 cm H2O from 50 to 0 mm Hg and was recorded with each of these instruments: the hand-held applanation tonometer, the Tono-pen XL, and the pneumatonometer. RESULTS: The Tono-pen XL and the hand-held applanation tonometer underestimated the IOP, whereas the pneumatonometer slightly overestimated IOP. Under close stopcock conditions, at IOPs between 3 and 30 mm Hg, the Tono-pen XL was as accurate as the pneumatonometer but had a smaller variance; the hand-held applanation tonometer had lower accuracy and higher variability. CONCLUSIONS: The Tono-pen XL is the tonometer of choice for measuring IOP in rabbits within the range of IOP 3 to 30 mm Hg. All tonometers were less accurate when the IOP was elevated markedly.
Asunto(s)
Presión Intraocular , Tonometría Ocular/instrumentación , Animales , Conejos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Dissociated cultures of mouse retinal neurons and photoreceptors in chemically defined medium were used to investigate the susceptibility of these cells to the neurotoxin kainic acid (KA). Cells isolated from the newborn mouse retina were initially insensitive to this toxin, and the cells that differentiated as rod photoreceptors retained this resistance throughout the culture period. However, amacrine neurons became increasingly sensitive to KA toxicity as they differentiated in culture; after the fifth day in vitro approximately 90% of these cells were killed by KA in a concentration- and time-dependent fashion. The neurons showed pronounced swelling within 10 min of treatment onset, and cell lysis and nuclear fragmentation were evident during the next few hours. KA-induced degeneration of these neurons was corroborated using the amacrine cell-specific monoclonal antibody HPC-1, as well as autoradiographic and biochemical determinations of the high affinity uptake for GABA. This inhibitory neurotransmitter was taken up by amacrine neurons but not by photoreceptor cells, and this uptake was completely abolished in KA-treated cultures. Similar results were obtained with the neuronal enzyme choline acetyltransferase. However, both photoreceptor survival and the expression of photoreceptor markers such as opsin and the retinoid-binding protein interphotoreceptor (IRBP) were similar in KA-treated and control cultures. Similarly, the high affinity uptake of glutamate, an excitatory amino acid which is predominantly taken up by photoreceptors, showed only modest changes in KA-treated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ácido Kaínico/toxicidad , Neuronas/efectos de los fármacos , Células Fotorreceptoras/efectos de los fármacos , Retina/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colina O-Acetiltransferasa/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neurotransmisores/metabolismo , Células Fotorreceptoras/citología , Células Fotorreceptoras/metabolismo , Retina/citología , Retina/metabolismo , Factores de TiempoRESUMEN
Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).
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Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 15 , Alelos , Niño , Análisis Citogenético , Femenino , Marcadores Genéticos , Genotipo , Humanos , Hibridación Fluorescente in Situ/métodos , MasculinoRESUMEN
For the past 25 years an emergency pulmonary embolectomy service has been offered to the hospitals serving a conurbation of 1.5 million. Fifty-five of these procedures have been performed during a short period of normothermic circulatory standstill produced by clamping the superior and inferior venae cavae. Of 36 patients who underwent pulmonary embolectomy without an episode of asystole or ventricular fibrillation, 35 survived the operation (97.2%). However, there were seven deaths during the postoperative period, three related to pulmonary embolism and four to other causes (mortality 20%). Conversely, in a group of 19 patients who had an episode of cardiac arrest, 14 died during or after the operation of pulmonary embolism and two of unrelated causes (mortality 73.7%). In properly selected patients this technique achieves a satisfactory measure of success. It can be used in hospitals that do not have cardiac surgical facilities and, because of its simplicity, it can be performed during the early period after pulmonary embolism when the risk of death is greatest.
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Embolia Pulmonar/cirugía , Adolescente , Adulto , Anciano , Errores Diagnósticos , Femenino , Humanos , Masculino , Métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Embolia Pulmonar/diagnóstico , Fibrilación Ventricular/mortalidadRESUMEN
Since 1984 five patients who had previously had cavopulmonary shunts for cyanotic congenital heart disease have returned to the Birmingham Childrens' Hospital with increasing breathlessness and cyanosis. Two had had a classic Glenn (unidirectional) cavopulmonary shunt and three, a bidirectional shunt; all shunts had been performed 5 to 18 years earlier. Each patient was reinvestigated and underwent creation of a brachial artery-basilic vein fistula. This procedure is known to have good patency rates when used in other situations (for example, for hemodialysis), but it has not been previously described for use in this context. Of the five patients, four had a considerable and sustained symptomatic improvement on follow-up of 12 to 49 months (mean 31 months), but the condition of one continued to deteriorate; that child has subsequently undergone a Fontan procedure, also with no improvement. Only one patient complained of coldness of the arm, and there were no other complications. We believe a brachial artery-basilic vein fistula has considerable advantages in terms of ease of operation and postoperative complications when compared with an axillary arteriovenous fistula, used as a supplement to an inadequate cavopulmonary shunt.
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Derivación Arteriovenosa Quirúrgica/métodos , Cardiopatías Congénitas/cirugía , Adolescente , Adulto , Brazo/irrigación sanguínea , Arteria Braquial/cirugía , Niño , Femenino , Humanos , Masculino , Complicaciones Posoperatorias , Arteria Pulmonar/cirugía , Reoperación , Venas/cirugía , Vena Cava Superior/cirugíaRESUMEN
In 42 children with congenital heart disease coagulation factor levels were studied serially during the first 20 hours following cardiopulmonary bypass surgery. The acyanotic patients, and also cyanotic patients who survived the operation, showed a progressive improvement in their coagulation profile from initial low postoperative levels. In 12 cyanotic patients who died within 72 hours, however, the coagulation factor levels either remained low, or fell further, until death. Fresh frozen plasma was administered to eight of these patients without apparent benefit. The abnormal coagulation profile correlated significantly with low skin temperature and increased blood loss and was considered to represent excess intravascular coagulation secondary to low cardiac output and poor tissue perfusion.
Asunto(s)
Trastornos de la Coagulación Sanguínea/complicaciones , Puente Cardiopulmonar , Circulación Extracorporea , Cardiopatías Congénitas/complicaciones , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/terapia , Plaquetas , Transfusión Sanguínea , Niño , Preescolar , Cianosis/etiología , Coagulación Intravascular Diseminada/complicaciones , Factor V/análisis , Factor VIII/análisis , Fibrina/análisis , Fibrinógeno/análisis , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/cirugía , Hematócrito , Heparina/sangre , Humanos , Lactante , Microscopía de Contraste de Fase , Plasminógeno/análisis , Protaminas/uso terapéutico , Temperatura CutáneaRESUMEN
BACKGROUND: A review of the literature and an extensive Medline search revealed that this is the first case report of fetal seizures diagnosed by ultrasound. CASE: A 23-year-old woman was found to have a fetus with bilateral choroid plexus cysts during a second-trimester ultrasound examination. Karyotype and alpha-fetoprotein level were normal. The cysts resolved, but idiopathic polyhydramnios was noted. Fetal testing beginning at 32 weeks revealed abnormal fetal behavior patterns on ultrasound and documented fetal seizures with rapid, repetitive limb movements noted on several occasions and lasting 30-60 seconds. Similar movements continued after birth as tonic-clonic seizure activity. CONCLUSION: Qualitative changes in movement patterns are common in neurologically impaired fetuses. Ultrasound may be used to diagnose these neurologic abnormalities that can be connected with clinical outcomes. This will better prepare the parents and hospital staff members for delivery and may also decrease medicolegal risk for the obstetrician because the abnormal behavior predates the birth process.
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Enfermedades Fetales/diagnóstico por imagen , Convulsiones/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Encéfalo/anomalías , Femenino , Humanos , Recién Nacido , Polihidramnios/diagnóstico por imagen , Embarazo , Convulsiones/etiologíaRESUMEN
The primary objective of this open-label study was to determine the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE)following two consecutive applications of a contraceptive patch (ORTHO EVRA/EVRA). Twelve healthy women wore the first patch on their abdomen for 7 days and, after removal at 168 hours (day 7), wore a second patch for 10 days (i.e., 3 days beyond the intended 7-day wear period). Blood samples were collected before and at various times up to 456 hours (day 19) after application of the first patch for analysis of NGMN and EE. Mean serum concentrations of NGMN and EE remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the entire 7-day wear period after application of the first patch and for 10 days after application of the second patch; reference ranges are based on studies with ORTHO-CYCLEN/ Cilest. No patch detached spontaneously. No subject discontinued or experienced a serious adverse event.
Asunto(s)
Anticonceptivos Orales Combinados/farmacocinética , Congéneres del Estradiol/farmacocinética , Etinilestradiol/farmacocinética , Administración Cutánea , Adolescente , Adulto , Área Bajo la Curva , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/sangre , Combinación de Medicamentos , Congéneres del Estradiol/administración & dosificación , Congéneres del Estradiol/sangre , Etinilestradiol/administración & dosificación , Etinilestradiol/sangre , Etisterona/análogos & derivados , Femenino , Humanos , Norgestrel/análogos & derivados , Oximas , Factores de TiempoRESUMEN
The objectives of this randomized, open-label, three-period, incomplete block design study were to evaluate the pharmacokinetics of norelgestromin (NGMN) and ethinyl estradiol (EE) delivered by the contraceptive patch, Ortho Evra/Evra, and to evaluate patch adhesion under conditions of heat, humidity, and exercise. During each treatment period, 30 healthy women wore Ortho Evra on the abdomen for 7 days under one of six conditions (normal activity, sauna, whirlpool, treadmill, cool water immersion, or a combination of activities). Blood samples were collected before and several times to 240 hours after patch application. Mean serum concentrations of NGMN and EE generally remained within the reference ranges, 0.6 to 1.2 ng/ml and 25 to 75 pg/ml, respectively, during the 7-day wearperiodfor all activities. Only 1 (1.1%) of 87 patches completely detached spontaneously. Peel force measurements were comparable for all activities. Ortho Evra was well tolerated. In conclusion, Ortho Evra delivers efficacious concentrations of NGMN and EE and maintains adhesive reliability through 7 days of wear even under conditions of heat, humidity, and exercise.
Asunto(s)
Anticonceptivos Orales Combinados/farmacocinética , Congéneres del Estradiol/farmacocinética , Etinilestradiol/farmacocinética , Ejercicio Físico/fisiología , Calor , Adhesividad , Administración Cutánea , Adulto , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/efectos adversos , Combinación de Medicamentos , Congéneres del Estradiol/administración & dosificación , Congéneres del Estradiol/efectos adversos , Etinilestradiol/administración & dosificación , Etinilestradiol/efectos adversos , Etisterona/análogos & derivados , Femenino , Humanos , Humedad , Persona de Mediana Edad , Norgestrel/análogos & derivados , OximasRESUMEN
This review summarizes the clinical studies involving the once-weekly Ortho Evra/Evra contraceptive patch. The patch delivers norelgestromin (NGMN), 150 microg, and ethinyl estradiol (EE), 20 microg, daily to the systemic circulation. The contraceptive patch provided ovulation suppression and cycle control similar to that of oral norgestimate 250 microg/EE 35 microg, significantly decreased mean maximum follicular diameter following a 3-day intentional delayed dosing phase when compared with oral levonorgestrel (LNG) 50/75/125 microg/EE 30/40/30 micorg and oral LNG 100 microg/EE 20 microg, and was as effective as oral LNG 50/75/125 microg/EE 30/40/30 microg and oral desogestrel 150 microg/EE 20 microg in altering cervical mucus composition (i.e., creating a scanty, viscous consistency). The contraceptive patch provided efficacy, cycle control, and safety comparable to that seen with oral LNG 50/75/125 microg/EE 30/40/30 microg, but women were able to correctly follow the weekly dosing regimen significantly more often than the daily oral contraceptive dosing regimen. Less than 2% of patches were replaced because of complete detachment in these trials. The patch was not associated with phototoxicity or photoallergy. The contraceptive patch, the only noninvasive, weekly birth control method that a woman can self-administer, will be a valuable addition to current contraceptive options.
Asunto(s)
Anticonceptivos Femeninos/farmacocinética , Etinilestradiol/farmacocinética , Administración Cutánea , Ensayos Clínicos como Asunto , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/sangre , Anticonceptivos Orales Combinados/farmacocinética , Esquema de Medicación , Combinación de Medicamentos , Implantes de Medicamentos , Interacciones Farmacológicas , Etinilestradiol/administración & dosificación , Etinilestradiol/sangre , Etisterona/análogos & derivados , Femenino , Humanos , Norgestrel/análogos & derivados , Oximas , Embarazo , SeguridadRESUMEN
The photochemistry of tetraphenylacetone (1) adsorbed on the external surface of a MFI zeolite (the sodium form of LZ-105) has been investigated in combination with computational chemistry, surface area measurements, EPR analysis, and classical adsorption isotherms. All of the methods are consistent with a supramolecular structural model in which 1 is first adsorbed strongly through intercalation of a single benzene ring into a hole on the LZ-105 external surface (site I) followed by a weaker binding to the external framework between the holes (site II) until a monolayer of 1 is formed. From both computational and surface area measurements, it is estimated that the site I holes on the external surface will be filled at ca. 0.3-0.5 wt %/wt loading of 1/LZ-105, which corresponds to 6.5 x 10(18) (ca. 10(-)(5) mol) of holes or molecules of 1 adsorbed in holes per gram of zeolite. The supramolecular composition of ca. 0.3-0.5% of 1 on LZ-105 characterizes a "break point" for the photochemistry and the EPR measurements, since it represents the value for saturation of the site I holes with 1. These conclusions are supported quantitatively by experimental isotherms of the adsorption of 1 on LZ-105. Photolysis of 1 intercalated in the site I holes causes fragmentation into two isomeric supramolecular diphenylmethyl (DPM) radicals, one (DMP)(in) which is adsorbed into the internal surface and becomes strongly persistent (half-life of many weeks) and the other (DMP)(ex) which diffuses on the external surface and rapidly dimerizes (less than a few minutes) to produce the radical-radical combination product tetraphenylethane (2). Photolysis of 1 adsorbed on the solid external surface produces two supramolecularly equivalent DPM radicals (DMP)(ex) that diffuse on the external surface and rapidly dimerize to produce 2, and do not produce persistent DPM radicals.
RESUMEN
This study developed and tested a Transmission Deficit hypothesis of how aging affects retrieval of orthographic knowledge. Young, older, and very old adults heard a tape-recorded series of difficult-to-spell words of high and low frequency, spoken slowly, clearly and repeatedly, and wrote down each word at their own pace. With perceptual errors and vocabulary differences factored out, misspellings increased with aging, especially for high-frequency words. In addition, data from a metamemory questionnaire indicated that the oldest adults were aware of their declining ability to spell. These findings were not due to general slowing, educational factors, hours per week spent reading, writing, or solving crossword puzzles, or age-linked declines in monitoring or detecting self-produced errors. However, the results fit Transmission Deficit predictions, and suggested an age-linked decline in retrieval of orthographic knowledge that resembles age-linked declines in spoken word retrieval observed in many other studies. Practical implications of this age-linked decline for conceptions of normal aging are noted.
Asunto(s)
Envejecimiento/fisiología , Memoria/fisiología , Reconocimiento Visual de Modelos/fisiología , Fonética , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/psicología , Análisis de Varianza , Educación , Femenino , Humanos , Masculino , Procesos Mentales , Persona de Mediana Edad , Modelos Psicológicos , Lectura , Encuestas y Cuestionarios , EscrituraRESUMEN
This experiment tested for age-linked asymmetries predicted under Node Structure theory (NST; D. G. MacKay & D. M. Burke, 1990) between detecting versus retrieving orthographic information. Older adults detected that briefly presented words were correctly spelled (e.g., endeavor) or misspelled (e.g., endeavuor) as readily as did young adults. However, they were less able than young adults to retrieve the correctly and incorrectly spelled words that they had seen. These age-linked asymmetries were not due to educational factors, stimulus characteristics, sensory-level factors, task complexity, floor or ceiling effects, general slowing, or cohort-related activities, but they were consistent with NST predictions and with similar asymmetries in a wide range of other studies. By contrast, repetition deficits in detecting and retrieving repeated- versus unrepeated-letter misspellings (e.g., elderdly vs. elderkly) were symmetrical or equivalent in magnitude for young and older adults. Implications for a wide range of theories of cognitive aging and of repetition deficits are discussed.