RESUMEN
BACKGROUND: There is little existing research on the role that secondary care letters have in ensuring patient understanding of chronic health conditions. AIM: To determine whether minimising the use of medical terminology in medical correspondence improved patient understanding and anxiety/depression scores. METHODS: A single-centre, non-blinded, randomised crossover design assessed health literacy, EQ-5D scores and the impact of the 'translated' letter on the doctor's professionalism, the patient's relationship with their general practitioner (GP) and their perceived impact on chronic disease management. Patients were crossed over between their 'translated' and original letter. RESULTS: Sixty patients were recruited. Use of a 'translated' letter reduced mean terms not understood from 7.78 to 1.76 (t(58) = 4.706, P < 0.001). Most patients (78.0%) preferred the 'translated' letter, with 69.5% patients perceiving an enhancement in their doctor's professionalism (z = 2.864, P = 0.004), 69.0% reporting a positive influence on relationship with their GP (z = 2.943, P = 0.003) and 79.7% reporting an increase in perceived ability to manage their chronic health condition with the 'translated' letter (z = 4.601, P < 0.001). There was no effect on EQ-5D depression/anxiety scores. CONCLUSION: Minimising the use of medical terminology in medical correspondence significantly improved patient understanding and perception of their ability to manage their chronic health condition. Although there was no impact on EQ-5D depression/anxiety scores, overwhelming patient preference for the 'translated' letter indicates a need for minimisation of medical terminology in medical correspondence for patients with chronic health conditions.
Asunto(s)
Comunicación , Alfabetización en Salud , Atención Secundaria de Salud , Terminología como Asunto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/terapia , Estudios Cruzados , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Medición de Resultados Informados por el Paciente , Atención Dirigida al Paciente , Calidad de Vida , Análisis de RegresiónRESUMEN
We report here a semi-automated process by which mouse genome feature predictions and curated annotations (i.e., genes, pseudogenes, functional RNAs, etc.) from Ensembl, NCBI and Vertebrate Genome Annotation database (Vega) are reconciled with the genome features in the Mouse Genome Informatics (MGI) database (http://www.informatics.jax.org) into a comprehensive and non-redundant catalog. Our gene unification method employs an algorithm (fjoin--feature join) for efficient detection of genome coordinate overlaps among features represented in two annotation data sets. Following the analysis with fjoin, genome features are binned into six possible categories (1:1, 1:0, 0:1, 1:n, n:1, n:m) based on coordinate overlaps. These categories are subsequently prioritized for assessment of annotation equivalencies and differences. The version of the unified catalog reported here contains more than 59,000 entries, including 22,599 protein-coding coding genes, 12,455 pseudogenes, and 24,007 other feature types (e.g., microRNAs, lincRNAs, etc.). More than 23,000 of the entries in the MGI gene catalog have equivalent gene models in the annotation files obtained from NCBI, Vega, and Ensembl. 12,719 of the features are unique to NCBI relative to Ensembl/Vega; 11,957 are unique to Ensembl/Vega relative to NCBI, and 3095 are unique to MGI. More than 4000 genome features fall into categories that require manual inspection to resolve structural differences in the gene models from different annotation sources. Using the MGI unified gene catalog, researchers can easily generate a comprehensive report of mouse genome features from a single source and compare the details of gene and transcript structure using MGI's mouse genome browser.
Asunto(s)
Bases de Datos Genéticas , Genoma , Genómica/métodos , Programas Informáticos , Algoritmos , Animales , Genómica/estadística & datos numéricos , Internet , Ratones , Modelos Genéticos , Anotación de Secuencia Molecular , Sistemas de Lectura Abierta , Seudogenes , ARN/genética , Terminología como AsuntoRESUMEN
We demonstrate broadband (20 THz), high electric field, terahertz generation using large area interdigitated antennas fabricated on semi-insulating GaAs. The bandwidth is characterized as a function of incident pulse duration (15-35 fs) and pump energy (2-30 nJ). Broadband spectroscopy of PTFE is shown. Numerical Drude-Lorentz simulations of the generated THz pulses are performed as a function of the excitation pulse duration, showing good agreement with the experimental data.
Asunto(s)
Diseño Asistido por Computadora , Rayos Láser , Iluminación/instrumentación , Radiación Terahertz , Transductores , Conductividad Eléctrica , Diseño de Equipo , FotonesRESUMEN
OBJECTIVE: Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD). METHODS: Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937. RESULTS: Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), P<0.0001). More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P<0.0001), and 50.5% versus 21.8% of participants lost ≥5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P<0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity. CONCLUSION: Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Restricción Calórica , Terapia por Ejercicio , Péptido 1 Similar al Glucagón/análogos & derivados , Obesidad/prevención & control , Pérdida de Peso , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fármacos Antiobesidad/administración & dosificación , Restricción Calórica/métodos , Canadá/epidemiología , Método Doble Ciego , Esquema de Medicación , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/uso terapéutico , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/terapia , Resultado del Tratamiento , Estados Unidos/epidemiología , Pérdida de Peso/efectos de los fármacosRESUMEN
AIMS: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years. METHODS: Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. RESULTS: For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). CONCLUSION: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.
Asunto(s)
Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/administración & dosificación , Hipoglucemiantes/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Glucemia/fisiología , Peso Corporal/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Femenino , Hemoglobina Glucada , Humanos , Liraglutida , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Chemoradiotherapy is a widely used alternative treatment to surgical resection in certain patient groups with early esophageal cancer. The aim of this study was to retrospectively assess toxicity and outcome of patients treated with definitive chemoradiotherapy for early esophageal cancer at one institution. A retrospective analysis of all patients treated with chemoradiotherapy between February 2000 and December 2008 at a single tertiary center was performed with documentation of treatment given, toxicities recorded, and follow-up and outcome data. Sixty-two patients received chemoradiotherapy for esophageal cancer. There were 20 males and 42 female patients with an average age of 68 years. Histology revealed adenocarcinoma in 28 patients and squamous cell carcinoma in 34 patients. All patients were staged with a computerized tomography scan, endoscopic ultrasound and positron emission tomography scan. Selection criteria for chemoradiotherapy were unfit for surgery, upper esophageal squamous carcinoma, unresectable primary tumor, or patient choice. The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 55 Gy in 25 fractions of radiotherapy. Grade 3 toxicities were recorded in 11% of the patients. Eleven patients suffered from local recurrence and a stent was required in nine patients. Radiation strictures occurred in 10 patients requiring dilation in four. Five patients required a radiologically inserted feeding gastrostomy. The median overall survival was 21 months. Patients with adenocarcinomas and those with squamous cell carcinoma had a similar median survival. Overall survival was 70% at 1 year, 48% at 2 years, and 26% at 3 years. This case series of patients treated with chemoradiation for localized esophageal cancer suggest a generally well-tolerated treatment with survival rates after chemoradiotherapy comparable with those seen with surgery.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Terapia Combinada/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Esquema de Medicación , Epirrubicina/administración & dosificación , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We investigate the nonlinear optical properties of graphene flakes using four-wave mixing. The corresponding third-order optical susceptibility is found to be remarkably large and only weakly dependent on the wavelength in the near-infrared frequency range. The magnitude of the response is in good agreement with our calculations based on the nonlinear quantum response theory.
RESUMEN
AIM: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. METHODS: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). RESULTS: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [-0.84 (0.08)%] and 1.8 mg [-1.14 (0.08)%] than glimepiride [-0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: -2.05 (0.28) kg; 1.8 mg: -2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331-0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41-0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. CONCLUSIONS: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/uso terapéutico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/uso terapéutico , Compuestos de Sulfonilurea/efectos adversos , Método Doble Ciego , Femenino , Hemoglobina Glucada , Humanos , Hipoglucemia/tratamiento farmacológico , Liraglutida , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Aumento de Peso/efectos de los fármacosAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/economía , Niño , Análisis Costo-Beneficio , Países en Desarrollo/economía , Farmacorresistencia Viral , Infecciones por VIH/economía , Infecciones por VIH/prevención & control , Accesibilidad a los Servicios de Salud , HumanosRESUMEN
Antibody-dependent, cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was analyzed in terms of the ability of autochthonous antibody to induce or potentiate cytotoxicity by lymphocytes from animals infected with MSV. As previously demonstrated in microcytotoxicity assays, the lymphocytes from regressor animals taken 30 days after virus infection were consistently more cytotoxic than those from tumor-bearing animals 15 days after infection. Antisera from the regressors potentiated the activity of regressor lymphocytes from the same animals. Also, antisera from tumor bearers, 15 days after virus injection, induced cytotoxicity by the animals' autochthonous lymphocytes which, by themselves, were not cytotoxic. In an independent assay for antibody, both groups of sera produced cytotoxicity by control nonimmune lymphocytes. Specificity controls indicated that both antibody and lymphocytes were required for the induction of cytotoxicity against the target cells in vitro. Normal sera placed on the target cells in the same concentrations induced no cytotoxicity by the immune lymphocytes, and immune sera alone placed on the target cells caused no cytotoxicity. The cooperative activity between antibody and lymphocytes may be a factor that accounts for the observed high incidence of spontaneous tumor regression.
Asunto(s)
Anticuerpos Antineoplásicos , Linfocitos/inmunología , Virus de la Leucemia Murina de Moloney/inmunología , Sarcoma Experimental/inmunología , Animales , Pruebas Inmunológicas de Citotoxicidad , Ratones , Ratones Endogámicos CBA , Factores de TiempoRESUMEN
An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients.
Asunto(s)
Ataxia Telangiectasia/genética , Cromátides/efectos de la radiación , Daño del ADN , Interfase/efectos de la radiación , Adolescente , Adulto , Anciano , Niño , Femenino , Heterocigoto , Humanos , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Tolerancia a RadiaciónRESUMEN
A review of emergency department visits during a 2-year period and before and after the liberation of physicians from a requirement of gatekeeping for some patients during the night showed no significant increases in the use or costs of services to our Medicaid enrollees for all but children under 6 years of age between 10 PM and midnight. We recommend that a more humane and practical view be taken of middle-of-the-night gatekeeping requirements for physicians functioning in managed-care environments. We also suggest, as many hospitals have already learned, that the costs of emergency department services for Medicaid patients can be reduced and that care may be enhanced by the offering of 24-hour urgent care services at or near the emergency department.
Asunto(s)
Actitud del Personal de Salud , Servicio de Urgencia en Hospital/estadística & datos numéricos , Medicaid/economía , Médicos/psicología , Derivación y Consulta , Adulto , Niño , Control de Costos , Servicio de Urgencia en Hospital/economía , Servicio de Urgencia en Hospital/organización & administración , Humanos , Programas Controlados de Atención en Salud , Calidad de Vida , Estados UnidosRESUMEN
GH is believed to play a role in promoting insulin resistance in patients with diabetes and with GH excess. The means by which GH produces insulin resistance may be through direct suppression of glucose metabolism in target cells (insulin-independent) or by interfering with the ability of insulin to stimulate glucose metabolism (insulin-dependent). In 3T3-F442A adipocytes, long term incubation (24-72 h) with GH directly inhibits glucose oxidation and lipid synthesis in the absence of insulin. To distinguish the insulin-independent effects of GH on glucose metabolism from the insulin-dependent effects of GH, we examined the effect of GH on insulin-stimulated lipid accumulation in cultured 3T3-F442A adipocytes. Cells were incubated for 48-72 h with GH and then treated with insulin. Insulin stimulated lipid accumulation in GH-pretreated and control cells. Compared to control, GH-treated cells had lower absolute levels of lipid accumulation in the absence of insulin and at each insulin concentration tested. Thus, GH directly suppresses basal lipid accumulation and lowers the response to insulin. In addition, a 10 times higher insulin concentration was required to reach maximum stimulation of lipid accumulation in GH-treated cells (50 ng/ml) than in control cells (5 ng/ml). When cells were exposed simultaneously to insulin and GH for 72 h, GH treatment inhibited the ability of insulin to stimulate lipid accumulation, and the degree of suppression by GH was related to the GH concentration present. These observations suggest that GH suppresses glucose metabolism not only in the absence but also in the presence of insulin. Since short term (4-h) incubation with GH increases glucose metabolism transiently in GH-deficient preparations, we also examined the influence of short term incubation with GH on insulin responses. Cells were incubated for 4 h with varying concentrations of insulin in the simultaneous presence or absence of GH. Insulin stimulated the conversion of glucose to lipid when tested alone or in the presence of GH. Short term exposure to GH alone also stimulated glucose metabolism. The stimulation of lipid accumulation at insulin concentrations less than 5 ng/ml was greater with GH, but responses were comparable above 5 ng/ml insulin. The ability of insulin to bind to its receptor was not affected by prior treatment with GH for either short or prolonged time periods.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Tejido Adiposo/metabolismo , Glucosa/metabolismo , Hormona del Crecimiento/farmacología , Insulina/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Embrión de Mamíferos , Humanos , Insulina/metabolismo , Lípidos/biosíntesis , Ratones , Oxidación-Reducción , Proteínas RecombinantesRESUMEN
Gonadotropin secretion is pulsatile in prepubertal and early pubertal boys, and the onset of puberty is characterized by a sleep-associated rise in LH pulse amplitude. To determine whether an augmentation in LH pulse frequency as well as amplitude occurs at the onset of puberty, we studied gonadotropin secretion in 21 early to midpubertal boys. Blood samples were taken every 20 min (every 15 min in 4 boys) for LH determinations. A 2-fold increase in LH pulse frequency occurred during the nighttime sampling period (2200-0400 h) compared to that in the hours when the boys were awake (1000-2200 h). The maximum frequency (0.7 pulses/h) occurred between 2400 and 0200 h. The mean plasma LH concentration increased during the night from 2.3 +/- 0.2 (+/- SE) mIU/mL (2.3 +/- 0.2 IU/L) between 2000-2200 h to a maximum of 6.2 +/- 0.4 (6.2 +/- 0.4 IU/L) between 0200-0400 h. The mean plasma LH decreased to 5.5 +/- 0.4 mIU/mL (5.5 +/- 0.4 IU/L) between 0400-0600 h and to 4.2 +/- 0.5 (4.2 +/- 0.5 IU/L) between 0600-0800 h. Plasma testosterone rose during the night to a mean maximum value of 2.4 +/- 0.5 (+/- SE) ng/mL (8.3 +/- 1.7 nmol/L). This finding suggested that the rise in testosterone might play a role in decreasing LH secretion during the later hours of sleep (after 0400 h). To address this question and to study further the effects of testosterone in early puberty, we measured plasma LH concentrations every 10 min from 2000-0800 h in 8 early to mid-pubertal boys before and during short term testosterone administration. Saline or testosterone at a concentration of 9.33 micrograms/mL (32 mumol/L) was infused at a rate of 10 mL/h from 2100-1200 h to shift the nighttime testosterone rise 3 h earlier than would occur spontaneously. Blood samples were obtained every 10 min for LH and every 30 min for testosterone determinations from 2000-0800 h. Pituitary responsiveness was assessed by administering sequential doses of synthetic GnRH (25 and 250 ng/kg) at 1000 and 1200 h, respectively. The nighttime increase in LH pulse frequency and mean plasma LH concentration occurred between 2300 and 0200 h despite testosterone infusion. However, testosterone infusion was associated with significantly lower mean plasma LH concentrations from 0200-0800 h compared to those on the night of the saline infusion. Pituitary responsiveness to synthetic GnRH was unaltered by testosterone administration.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Hormona Luteinizante/metabolismo , Pubertad/metabolismo , Sueño/fisiología , Testosterona/farmacocinética , Adolescente , Niño , Humanos , MasculinoRESUMEN
Administration of testosterone (T) can inhibit LH secretion in early pubertal boys. However, the GnRH pulse generator is relatively resistant to the effects of T, since T infusion beginning at 2100 h, 3 h before the usual nighttime increase in T, does not suppress the characteristic increase in LH pulse frequency or amplitude associated with the onset of sleep in early pubertal boys. To test the hypothesis that the hypothalamic-pituitary axis must be exposed to T for a longer duration to suppress the nocturnal rise in LH pulse frequency and amplitude, we infused saline or T at one third the adult male production rate (320 nmol/h), beginning at 1200 h on two consecutive weekends in each of eight early to midpubertal boys. Blood was obtained from 2000-0800 h every 10 min for LH and every 30 min for T measurements. T infusion increased the mean plasma T concentration from 6.9 +/- 1.7 to 11.8 +/- 1.4 nmol/L (P less than 0.01) between 2000-0800 h. Despite the T infusion, the nocturnal rise in mean LH concentration and LH pulse frequency persisted, suggesting that the nocturnal amplification of LH, and by inference GnRH, secretion is resistant to the negative feedback effects of T. A higher dose of T, approximating the adult male production rate (960 nmol/h), was given to eight additional boys beginning at 1200 h. The mean T concentration increased from 4.2 +/- 1.7 to 20.8 +/- 3.1 (P less than 0.001) nmol/L between 2000-0800 h. The mean plasma LH concentration was suppressed by T infusion from 5.2 +/- 0.5 to 2.9 +/- 0.4 IU/L, and LH pulse frequency decreased from 0.50 +/- 0.04 to 0.27 +/- 0.11 pulses/boy/h (P less than 0.01). There was no nocturnal amplification of LH secretion, but high amplitude LH pulses did occur during the night in six of the eight boys. The low dose T infusion had no effect on pituitary LH release by exogenous GnRH. With the high dose T infusion, however, the ability of GnRH, at 25 ng/kg but not at 250 ng/kg, to release pituitary LH was amplified. Thus, T supplementation at one third the adult male production rate does not blunt the sleep-associated nighttime rise in LH pulse frequency or LH concentration. T infusion approximating the adult male production rate suppresses the nocturnal increase in LH pulse frequency and mean LH concentration, and high amplitude, slow frequency LH pulses similar to patterns seen in adult men persist.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Hormona Luteinizante/metabolismo , Pubertad Tardía/fisiopatología , Testosterona/farmacología , Adolescente , Hormona Liberadora de Gonadotropina , Humanos , Infusiones Intravenosas , Hormona Luteinizante/sangre , Masculino , Pubertad Tardía/sangre , Testosterona/administración & dosificaciónRESUMEN
Analyses of the intermediates of DNA replication of the R6K plasmid derivatives, RSF1040, RJHC12 and RJHC26 demonstrate the transient accumulation of open circular DNA molecules with a discontinuity in either the plus or the minus strand of the DNA. The location of this discontinuity is nonrandom and is near the terminus of DNA replication. The discontinuity is not due to the activation of a relaxation complex since neither RJHC12 nor RJHC26 are relaxable. The replication terminus is functional in a clone containing approx. a 2000 bp sub-fragment of the HindIII-2 fragment of R6K. The replication terminus temporarily arrests the progression of replication fork of the unidirectionally replicating plasmid pBR313 at a region approx. 800 bp from HindIII site located nearest to the BamHI site of the vector. Subcloning experiments reveal that the upper limit of the replication termination sequence is 216 bp in length.
Asunto(s)
Replicación del ADN , Plásmidos , Clonación Molecular/métodos , ADN Bacteriano/genética , ADN Circular/genéticaRESUMEN
Forty-five pregnancies in rhesus monkeys maintained in a semioutdoor environment and fed about 1, 2, or 4 g of protein/kilogram of body weight each day in otherwise equivalent diets were observed. The 4-g diet shortened gestation 8.5 days. Male infants were carried 6 days longer than females; part of difference can be attributed to their greater birthweight. Summer conception produced longer gestation than did winter conception. Large mothers carried their infants slightly longer than small ones.
Asunto(s)
Proteínas en la Dieta/administración & dosificación , Macaca mulatta/fisiología , Macaca/fisiología , Preñez , Animales , Peso al Nacer , Peso Corporal , Femenino , Fertilización , Edad Gestacional , Haplorrinos , Masculino , Embarazo , Estaciones del Año , Factores Sexuales , TemperaturaRESUMEN
The rate of overflow and disappearance of dopamine from the extracellular fluid of the rat striatum has been measured during neuronal stimulation. Overflow of dopamine was induced by electrical stimulation of the medial forebrain bundle with biphasic pulse trains. The instantaneous concentration of dopamine was measured with a Nafion-coated, carbon fiber microelectrode implanted in the brain. The measurement technique, fast-scan cyclic voltammetry, samples the concentration of dopamine in less than 10 ms at 100 ms intervals. Identification of dopamine is made with cyclic voltammetry. Stimulated overflow was measured as a function of electrode position, stimulation duration, stimulation frequency, and after administration of L-DOPA and nomifensine. The observed concentration during a 2-s, 60-Hz stimulation was found to alter with position of the carbon fiber electrode. For stimuli of 3 s or less the amount of overflow was found to be a linear function of stimulus duration at a fixed electrode position. The observed overflow was found to be steady-state at a frequency of 30 Hz, suggesting a balance between uptake and synaptic overflow under these conditions. The experimental data was found to be successfully modelled when the balance of uptake and stimulated overflow was considered. It was assumed that each stimulus pulse releases a constant amount of dopamine (125 nM), and that uptake follows a Michaelis-Menten model for a single uptake site with Km = 200 nM and Vmax = 5 microM/s. The increase in stimulated overflow observed after L-DOPA (250 mg/kg) could be modelled by a 1.6-fold increase in the amount of dopamine release with no alteration of the uptake parameters. The increase in modelled by an increase in Km. In addition, the fit of the modelled data to the experimental data was improved when diffusion from the release and uptake sites was considered.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Algoritmos , Animales , Estimulación Eléctrica , Electrofisiología , Espacio Extracelular/metabolismo , Cinética , Levodopa/farmacología , Masculino , Ratas , Ratas EndogámicasRESUMEN
An entirely automated 96-well microplate-based system to perform procedures for the measurement of protein is described. This single instrument system utilizes a series of computer-controlled mechanical subsystems to move the plate, control incubations and dispense samples or reagents in order to perform the assay. This system allows the investigator to reproducibly perform these protein assays on large numbers of biological samples with minimal effort.