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1.
Science ; 272(5263): 892-5, 1996 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-8629027

RESUMEN

Transcription factors of the NFAT family are thought to play a major role in regulating the expression of cytokine genes and other inducible genes during the immune response. The role of NFAT1 was investigated by targeted disruption of the NFAT1 gene. Unexpectedly, cells from NFAT1 -/- mice showed increased primary responses to Leishmania major and mounted increased secondary responses to ovalbumin in vitro. In an in vivo model of allergic inflammation, the accumulation of eosinophils and levels of serum immunoglobulin E were increased in NFAT1 -/- mice. These results suggest that NFAT1 exerts a negative regulatory influence on the immune response.


Asunto(s)
Proteínas de Unión al ADN/fisiología , Hipersensibilidad/inmunología , Inmunidad , Activación de Linfocitos , Proteínas Nucleares , Factores de Transcripción/fisiología , Secuencia de Aminoácidos , Animales , Antígenos de Protozoos/inmunología , Línea Celular , Citocinas/biosíntesis , Proteínas de Unión al ADN/genética , Eosinófilos/inmunología , Marcación de Gen , Inmunoglobulina E/biosíntesis , Memoria Inmunológica , Leishmania major/inmunología , Ratones , Datos de Secuencia Molecular , Factores de Transcripción NFATC , Ovalbúmina/inmunología , Linfocitos T/inmunología , Factores de Transcripción/genética
2.
J Clin Endocrinol Metab ; 85(4): 1505-12, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10770189

RESUMEN

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.


Asunto(s)
Remodelación Ósea/efectos de los fármacos , Colágeno/metabolismo , Doping en los Deportes , Hormona de Crecimiento Humana/farmacología , Adulto , Biomarcadores/sangre , Colágeno/sangre , Colágeno Tipo I , Análisis Discriminante , Método Doble Ciego , Femenino , Humanos , Masculino , Osteocalcina/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Placebos , Procolágeno/sangre
3.
J Clin Endocrinol Metab ; 84(8): 2596-602, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10443645

RESUMEN

The long term effects of GH replacement in adult GH-deficient (GHD) patients have not yet been clarified. We studied 21 GHD adults who originally took part in a randomized, double blind, placebo-controlled trial of GH treatment in 1987. After completion of that trial, 10 patients received continuous GH replacement for the subsequent 10 yr, whereas 11 did not. A group of 11 age- and sex-matched normal controls were also studied in 1987 and 1997. Lean body mass, as assessed by total body potassium measurement and computed tomography scanning of the dominant thigh, increased in the GH-treated group (P < 0.01 for both) only (P < 0.05 between groups for total body potassium). Low density lipoprotein cholesterol decreased in the GH-treated group (P < 0.05) only. Carotid intima media thickness was significantly greater (P < 0.05) in the untreated group than in the GH-treated group. Assessment of psychological well-being using the Nottingham Health Profile revealed improvement in overall score, energy levels, and emotional reaction in the GH-treated group compared with those in the untreated group (P < 0.02). In conclusion, GH treatment for 10 yr in GHD adults resulted in increased lean body and muscle mass, a less atherogenic lipid profile, reduced carotid intima media thickness, and improved psychological well-being.


Asunto(s)
Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Adulto , Presión Sanguínea/efectos de los fármacos , Composición Corporal , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
4.
J Clin Endocrinol Metab ; 86(1): 200-6, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11232001

RESUMEN

Circulating GH consists of multiple molecular isoforms, all derived from the one gene in nonpregnant humans. To assess the effect of a potent stimulus to pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age, 26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise. Exercise consisted of continuous cycle ergometry at approximately 80% of predetermined maximal oxygen uptake for 20 min. Serum was assayed for total, pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All isoforms increased during, peaked at the end, and declined after exercise. At peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH and 20-kDa GH were significantly longer than those for all other isoforms. We conclude that 1) all molecular isoforms of GH measured increased with and peaked at the end of acute exercise, with 22-kDa GH constituting the major isoform in serum during exercise; and 2) the proportion of non-22-kDa isoforms increased after exercise due in part to slower disappearance rates of 20-kDa and perhaps other non-22-kDa GH isoforms. It remains to be determined whether the various biological actions of different GH isoforms impact on postexercise homeostasis.


Asunto(s)
Ejercicio Físico/fisiología , Hormona de Crecimiento Humana/sangre , Educación y Entrenamiento Físico , Isoformas de Proteínas/sangre , Adulto , Ciclismo , Hormona de Crecimiento Humana/química , Humanos , Masculino , Peso Molecular , Factores de Tiempo
5.
J Clin Endocrinol Metab ; 85(1): 124-33, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10634375

RESUMEN

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9+/-1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P<0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum osteocalcin (net increase preexercise, +/-10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248-770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.


Asunto(s)
Huesos/metabolismo , Colágeno/metabolismo , Ejercicio Físico/fisiología , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/farmacología , Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/farmacología , Síndrome de Abstinencia a Sustancias/metabolismo , Adolescente , Adulto , Envejecimiento/metabolismo , Biomarcadores , Desarrollo Óseo/fisiología , Prueba de Esfuerzo , Hormonas/sangre , Humanos , Cinética , Masculino , Resistencia Física/fisiología , Aptitud Física/fisiología
6.
J Clin Endocrinol Metab ; 86(4): 1731-7, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11297610

RESUMEN

GH is being used by elite athletes to enhance sporting performance. To examine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration could be detected through suppression of non-22-kDa isoforms of GH, we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups. In identical exercise studies repeated between 24 and 96 h after cessation of treatment, the magnitude of the responses of all GH isoforms was suppressed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.


Asunto(s)
Hormona de Crecimiento Humana/química , Hormona de Crecimiento Humana/farmacología , Educación y Entrenamiento Físico , Isoformas de Proteínas/farmacología , Adulto , Ciclismo , Humanos , Masculino , Peso Molecular , Concentración Osmolar , Isoformas de Proteínas/sangre , Isoformas de Proteínas/química , Proteínas Recombinantes/farmacología
7.
J Clin Endocrinol Metab ; 83(1): 107-16, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9435425

RESUMEN

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. Patients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 +/- 1 yr (+/- SEM; range 17-67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 +/- 0.27 (range -8.8 +3.82; n = 78) to +1.08 +/- 2.87 (range -7.21 to +6.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment [17.6% and 68.9% with subnormal (< 2 SD) or normal (+/- 2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or dual energy x-ray absorptiometry (DEXA; P < 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P < 0.001) or deuterium dilution (P = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional reaction as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.


Asunto(s)
Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Calidad de Vida , Adulto , Análisis de Varianza , Australia , Presión Sanguínea , Densidad Ósea/efectos de los fármacos , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dexametasona , Método Doble Ciego , Emociones , Femenino , Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/sangre , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Placebos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Triglicéridos/sangre , Equilibrio Hidroelectrolítico/efectos de los fármacos
8.
J Clin Endocrinol Metab ; 84(10): 3591-601, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10523001

RESUMEN

GH abuse by elite athletes is currently undetectable. To define suitable markers of GH doping, we assessed the effects of acute exercise, GH administration, and GH withdrawal on the GH/insulin-like growth factor (IGF) axis in athletic adult males. Acute endurance-type exercise increased serum GH, GH-binding protein (GHBP), total IGF-I, IGF-binding protein (IGFBP)-3, and acid-labile subunit (ALS), each peaking at the end of exercise. IGFBP-1 increased after exercise was completed. Free IGF-I did not change with exercise. Recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum total IGF-I, IGFBP-3, and ALS, exaggerating the responses to exercise. IGFBP-2 and IGFBP-1 were trivially suppressed. After GH withdrawal, the GH response to identical exercise was suppressed. Total IGF-I, IGFBP-3, and ALS returned to baseline over 3-4 days. In summary, 1) acute exercise transiently increased all components of the IGF-I ternary complex, possibly due to mobilization of preformed intact complexes; 2) GH pretreatment augmented the exercise-induced changes in ternary complexes; 3) postexercise IGFBP-1 increments may protect against delayed onset hypoglycemia; 4) serum total IGF-I, IGFBP-3, and ALS may be suitable markers of GH abuse; and 5) differences in disappearance times altered the sensitivity of each marker for detecting GH abuse.


Asunto(s)
Ejercicio Físico , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/farmacología , Educación y Entrenamiento Físico , Somatomedinas/análisis , Adulto , Proteínas Portadoras/sangre , Glicoproteínas/sangre , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Cinética , Masculino , Resistencia Física , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Medicina Deportiva/métodos , Trastornos Relacionados con Sustancias/diagnóstico , Factores de Tiempo
9.
Neurology ; 44(11 Suppl 9): S60-8; discussion S68-9, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7970013

RESUMEN

Data from three placebo-controlled and 11 active-controlled studies of tizanidine were combined to permit analysis of the subsets, which were too small to evaluate within the individual studies. Overall analysis of placebo-controlled data confirms the effectiveness of tizanidine in reducing muscle tone in patients with spasticity of spinal cord origin. Subset analyses suggest that patients with more severe spasticity are more likely to respond, but age, sex, and race were not predictive of response. Comparisons of tizanidine with active controls showed no differences in efficacy compared with baclofen or diazepam. However, when compared with controls, patients treated with tizanidine did not experience increased weakness. Furthermore, patients tolerated tizanidine better than the control medications. More patients experienced adverse events during tizanidine treatment than did patients receiving placebo. The most common adverse events reported were dry mouth, somnolence, asthenia, and dizziness. Mild elevations in liver function tests were noted occasionally, but improved in all patients with dose reduction or withdrawal. Three patients from the double-blind database reported formed visual hallucinations. All three cleared; two continued tizanidine, and one discontinued.


Asunto(s)
Clonidina/análogos & derivados , Relajantes Musculares Centrales/uso terapéutico , Espasticidad Muscular/tratamiento farmacológico , Adulto , Anciano , Clonidina/efectos adversos , Clonidina/uso terapéutico , Ensayos Clínicos Controlados como Asunto , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relajantes Musculares Centrales/efectos adversos , Espasticidad Muscular/fisiopatología , Tono Muscular/fisiología , Mioclonía/prevención & control , Espasmo/prevención & control
10.
Neurology ; 53(7): 1431-8, 1999 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-10534247

RESUMEN

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.


Asunto(s)
Toxinas Botulínicas/uso terapéutico , Tortícolis/tratamiento farmacológico , Adulto , Anciano , Toxinas Botulínicas/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Evaluación de la Discapacidad , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Retratamiento , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tortícolis/fisiopatología
11.
Neurology ; 49(3): 701-7, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9305326

RESUMEN

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.


Asunto(s)
Antidiscinéticos/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Distonía/tratamiento farmacológico , Músculos del Cuello/fisiopatología , Tortícolis/tratamiento farmacológico , Adulto , Anciano , Antidiscinéticos/administración & dosificación , Toxinas Botulínicas/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Distonía/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos del Cuello/efectos de los fármacos , Dimensión del Dolor , Placebos , Índice de Severidad de la Enfermedad , Perfil de Impacto de Enfermedad , Resultado del Tratamiento
12.
Neurology ; 53(7): 1439-46, 1999 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-10534248

RESUMEN

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.


Asunto(s)
Toxinas Botulínicas/uso terapéutico , Tortícolis/tratamiento farmacológico , Adulto , Anciano , Toxinas Botulínicas/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Evaluación de la Discapacidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tortícolis/fisiopatología
13.
Eur J Endocrinol ; 141(1): 22-6, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10407218

RESUMEN

There is evidence that melatonin may play a role in modulating pituitary secretion, although the mechanisms are unclear. We examined the effects of a single dose of oral melatonin (5mg) on exercise-induced GH secretion. In a randomised, double-blind, placebo-controlled study, seven healthy male subjects undertook an initial period of graded bicycle ergometric exercise to determine maximum workload and oxygen uptake (VO(2max)). Subjects were subsequently studied on two further occasions, receiving either melatonin or placebo in random order at the onset of each study (-60min). At 0 min a period of bicycle exercise was performed for 8 min at a workload corresponding to 70% of that achieved at VO(2max). Serum GH and IGF-binding protein-1 (IGFBP-1) concentration was measured at 15-min intervals from the onset of the study until 120 min post-exercise. Blood was also sampled for the measurement of plasma glucose, insulin, non-esterified fatty acids, IGFBP-3, melatonin and vasopressin concentration. There was an exercise-induced increase in GH concentration following melatonin which was greater compared with placebo as assessed by both area under the curve (P<0.01) and peak increase in GH levels (P<0.01). The peak increase in IGFBP-1 levels post-exercise was also significantly greater following melatonin compared with placebo (P<0. 01) but did not quite reach levels of significance as measured by area under the curve (P=0.07). Since exercise-induced GH secretion is thought to be mediated predominantly through a hypothalamic pathway, it seems likely that melatonin facilitates GH secretion at a hypothalamic level.


Asunto(s)
Ejercicio Físico/fisiología , Hormona de Crecimiento Humana/metabolismo , Melatonina/farmacología , Adulto , Ciclismo , Glucemia/metabolismo , Método Doble Ciego , Ácidos Grasos no Esterificados/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Cinética , Masculino , Melatonina/administración & dosificación , Consumo de Oxígeno , Placebos , Vasopresinas/sangre
14.
Obstet Gynecol ; 48(2): 137-41, 1976 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-181701

RESUMEN

The first 18 months' experience of the Breast Diagnostic Center of Jefferson Medical College have been reviewed. Almost 14,000 patients were screened for breast disease, using a combination of clinical examination. Xeroradiography, and thermography. In this group of 14,000 women, 106 cases of cancer were discovered, in incidence of almost 8 per 1000 women screened. Of these 106 cases of cancer, 45.3% were clinically occult or not recognized by clinical examination, and within this group at the time of mastectomy only a small percent had any evidence of axillary lymph node metastases. The combination of several technics of examination is proving to be more reliable for the early detection of breast cancer than any of the technics alone, and programs such as these may make a significant difference in the death rate from breast cancer.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Tamizaje Masivo , Biopsia/métodos , Carcinoma in Situ/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , Femenino , Humanos , Metástasis Linfática , Mamografía , Pacientes Desistentes del Tratamiento , Examen Físico , Termografía , Xerorradiografía
15.
Epilepsy Res ; 14(2): 165-73, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8453952

RESUMEN

The safety and efficacy of zonisamide (ZNS), a new antiepileptic drug, was tested in 167 adult participants who entered a historical-controlled 16-week open label, multicenter study. The median percent reduction from baseline of partial seizures was 51.8% in the fourth month of the study (baseline median = 11.5 sz/month; treatment weeks 13-16 = 5.5 sz/month). Persons completing the efficacy study successfully were eligible for a long-term safety study; 113 entered this study. Adverse effects involved principally the CNS and were similar to those seen with other antiepileptic drugs. Four persons (3.7%) developed kidney stones and were withdrawn from the study 250-477 days after starting ZNS. Because of the high percentage of kidney stones, development of ZNS was stopped in the United States but was continued in Japan.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Isoxazoles/uso terapéutico , Adolescente , Adulto , Anciano , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Femenino , Humanos , Isoxazoles/administración & dosificación , Isoxazoles/efectos adversos , Masculino , Persona de Mediana Edad , Zonisamida
16.
Phys Med Biol ; 39(10): 1745-56, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15551542

RESUMEN

A Monte Carlo model has been developed, using the EGS4 code, to model the in vivo x-ray fluorescence (XRF) measurement of Pb in non-superficial bone/tissue. Unlike previous work in this field the current model incorporates a correction for Doppler broadening of the Compton scatter peak due to the electron momentum distribution of the medium (tissue/water) in which the photons are Compton scattered by convolving the Compton peak of the Monte Carlo generated spectrum with a modified Compton profile for water. This correction improves the agreement between the measured spectral shape obtained using an experimental in vivo x-ray fluorescence Pb analyser with a 109Cd/180 degrees source/geometry combination, measuring a bone phantom at depth in water and the generated spectral shape obtained from the equivalent Monte Carlo model. The model enables improved estimates to be made of the spectral background beneath the Pb Kalpha1 and Kalpha2 x-ray peaks compared with estimates based on simpler models that assume that Compton interactions are with 'free' electrons and hence permits better optimization of in vivo analyser system design.


Asunto(s)
Algoritmos , Tejido Conectivo/metabolismo , Diagnóstico por Computador/métodos , Intoxicación por Plomo/diagnóstico , Plomo/análisis , Modelos Biológicos , Método de Montecarlo , Espectrometría por Rayos X/métodos , Animales , Huesos/metabolismo , Simulación por Computador , Humanos , Modelos Estadísticos , Fantasmas de Imagen , Espectrometría por Rayos X/instrumentación
17.
J Anim Sci ; 76(5): 1247-53, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9621929

RESUMEN

Suffolk and Targhee ewes (30 each) with single or twin lambs were used in four periods beginning in late gestation and continuing through weaning to evaluate breed differences in milk production, lamb BW, and DMI by ewes and lambs. In Periods 1 (late gestation) and 2 (early lactation), ewes (Period 1) and ewes with lambs (Period 2) were individually penned, fed .45 kg of barley x ewe(-1) x d(-1) and allowed ad libitum access to chopped alfalfa. Ewes and lambs grazed native range in Periods 3 and 4. Grazed forage DMI was estimated using chromic oxide. Estimates of milk production were obtained by handmilking. Average lamb age was 4, 45, and 73 d at the beginning of Periods 2, 3, and 4, respectively. Milk production tended (P = .20) to be greater for Suffolk than for Targhee ewes. Targhee ewes produced 85% more (P = .001) wool than Suffolk ewes. From 33 d prepartum to 89 d postpartum, Suffolk ewes consistently weighed more (P = .001) than Targhee ewes. Suffolk ewe BW loss (-.15 kg/d) was greater (P = .01) than Targhee ewe BW loss (-.02 kg/d) from 33 d prepartum to 6 d postpartum. From 6 to 89 d postpartum BW gain did not differ (P = .69; .05 kg/d) between breeds. From birth to 89 d postpartum, Suffolk lambs consistently weighed more than Targhee lambs (P = .003). From birth to 89 d postpartum, ADG was greater for Suffolk than for Targhee lambs (P = .006). Targhee ewes consumed 25% more (P = .01) feed over the course of the study than did Suffolk ewes. Grazed forage DMI by Targhee lambs was 26% greater (P = .01) than DMI by Suffolk lambs. When meat production is the primary income from sheep, one potential advantage of Suffolks compared with Targhees is more rapid gain with less feed intake.


Asunto(s)
Animales Lactantes/fisiología , Ingestión de Alimentos/fisiología , Lactancia/fisiología , Ovinos/fisiología , Alimentación Animal , Animales , Peso Corporal , Cruzamiento , Dieta/normas , Dieta/veterinaria , Femenino , Leche/química , Poaceae , Periodo Posparto/fisiología , Gemelos , Lana/crecimiento & desarrollo
18.
J Anim Sci ; 71(10): 2601-7, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8226358

RESUMEN

Effects of cow BW, hip height, and estimated genetic potentials (EBV) for weaning weight direct and milk on cow productivity, fecal OM output, OM intake, and efficiency (kilograms of calf BW/kilogram of OM intake by the cow) were evaluated with 44 free-grazing crossbred cows under semidesert conditions. Calf BW were measured during early, mid-, and late lactation. Data were collected in four periods: Period 1 = late spring (early lactation), Period 2 = late summer (mid-lactation), Period 3 = mid-autumn (late lactation), and Period 4 = mid-winter (nonlactation). Calf BW increased linearly with cow BW (P < .01) in Periods 1, 2, and 3. Fecal OM output and OM intake increased with cow BW in Periods 2 (P < .01) and 4 (P < .01), and on average (P < .02). Overall efficiency decreased with increasing cow BW (P < .04). Taller cows excreted more fecal OM and had greater OM intake throughout the study (P < .02 to P < .11). Overall efficiency decreased with increasing cow hip height (P < .05). Weaning weight direct EBV of cows was related linearly to cow BW (P < .01 to P < .07) and to calf BW (P < .01 to P < .07). Calf weight in all periods increased linearly with milk EBV (P < .001). Overall, fecal OM output, OM intake, and efficiency were not affected by milk EBV.


Asunto(s)
Animales Lactantes/crecimiento & desarrollo , Peso Corporal , Bovinos/fisiología , Clima Desértico , Ingestión de Alimentos , Alimentación Animal , Animales , Cruzamiento , Bovinos/genética , Bovinos/crecimiento & desarrollo , Defecación , Femenino , Lactancia/genética , Lactancia/fisiología , Masculino , New Mexico , Poaceae , Destete
19.
J Anim Sci ; 69(3): 1167-77, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1648064

RESUMEN

In the first of two experiments, four wether lambs (BW = 26.8 kg) and four wether Angora goats (BW = 31.7 kg) were used in two simultaneous 4 x 4 Latin squares to study the influence of condensed tannins (CT) on nutrient usage and concentrations of serum urea N, somatotropin (GH), and insulin (INS) when the animals were fed low-quality diets containing mountain mahogany (MM; Cercocarpus montanus) leaves. Diets were 8% CP and contained 25% or 50% MM (with hay or straw, respectively), either untreated or treated with polyethylene glycol (PEG; molecular weight 3,350) to reduce total reactive CT. Diets treated with PEG and 25% MM diets had less (P less than .05) CT than diets without PEG or those with 50% MM. Diets containing 50% MM resulted in greater N balance and lower serum urea N (P less than .01) than 25% MM diets. Concentrations of GH and INS were similar in animals fed the 25% and 50% MM diets. Reducing CT by adding PEG did not affect N balance or improve nutrient digestion by lambs or goats fed low-quality diets. In Exp. 2, four wether lambs (BW = 28.4 kg) were used in a 4 x 4 Latin square and fed the same diets as animals in Exp. 1 to study the influence of CT on ruminal fermentation and digesta kinetics. Dietary PEG treatment did not affect digesta kinetics except for a 30% increase in ruminal volume; 50% MM diets had faster particulate passage rates (P less than .05) than 25% MM diets. Ruminal ammonia N was greater (P less than .01) in lambs fed PEG-containing or 25% MM diets; however, rate of in situ NDF disappearance was not reduced by the lower ammonia N in the latter diets.


Asunto(s)
Alimentación Animal , Digestión , Cabras/fisiología , Ovinos/fisiología , Taninos/metabolismo , Amoníaco/análisis , Animales , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/metabolismo , Ingestión de Alimentos , Ácidos Grasos Volátiles/análisis , Hormona del Crecimiento/sangre , Insulina/sangre , Masculino , Nitrógeno/metabolismo , Valor Nutritivo , Polietilenglicoles/farmacología , Rumen/química , Rumen/metabolismo , Urea/sangre
20.
J Anim Sci ; 69(3): 899-904, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2061260

RESUMEN

A study to examine the relationships between milk intake, forage intake, and performance of Hereford-Angus suckling range calves was conducted during July, August, and September of 1984 and 1985. Twenty calves were used each year. The study was conducted at the Red Bluff Research Ranch located 56 km west of Bozeman, Montana. Average daily gain, milk intake (MI), forage digestibility, and fecal output (FO) were measured at 28-d intervals, beginning when the average calf age was 66 +/- 4 d. Milk intake was estimated using weigh-suckle-weigh techniques. Total fecal collections were used to measure FO. Forage digestibility and rates of passage were determined using nylon bag in situ techniques and external markers in ruminally cannulated calves of the same age. Fecal output by calves increased as body weight and age increased. Milk intake was higher (P less than .05) in 1985 than in 1984, but FO was higher (P less than .01) in 1984 than in 1985. Fecal output by calves was negatively correlated to MI in July (r = -.62; P less than .05) and August (r = -.56; P less than .05). No significant correlations were detected between MI and ADG (P greater than .10). Forage intake estimates were derived from FO, rate of passage, and in situ digestibility values. During July, calves consumed .3 kg more forage for each kilogram of reduction in fluid MI (P less than .05). In both August and September, calves consumed .6 kg more forage for each kilogram of reduction in fluid MI (P less than .10). Calves maintained similar digestible energy (DE) intake both years, although the source of DE varied.


Asunto(s)
Alimentación Animal , Animales Lactantes/fisiología , Bovinos/fisiología , Ingestión de Alimentos , Leche , Animales , Animales Lactantes/crecimiento & desarrollo , Bovinos/crecimiento & desarrollo , Ingestión de Energía , Estaciones del Año , Aumento de Peso
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