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1.
Circulation ; 104(23): 2778-83, 2001 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-11733394

RESUMEN

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD18/inmunología , Infarto del Miocardio/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Circulación Coronaria/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Electrocardiografía , Femenino , Hemorragia/inducido químicamente , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento
2.
Am J Cardiol ; 87(5): 627-30, A9, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11230850

RESUMEN

In a retrospective cohort of patients treated in community hospitals, tissue plasminogen activator (t-PA) was associated with decreased odds of in-hospital death or nonfatal stroke. However, the relative benefit was less evident in older patients and women, and some older subgroups did not benefit from treatment.


Asunto(s)
Hemorragia Cerebral/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Activador de Tejido Plasminógeno/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores Sexuales , Activador de Tejido Plasminógeno/uso terapéutico
3.
Am J Cardiol ; 85(3): 294-8, 2000 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-11078295

RESUMEN

In acute myocardial infarction (AMI), immediate beta-blocker therapy reduces the incidence of reinfarction and recurrent chest pain in patients receiving tissue plasminogen activator (t-PA). Data from the Thrombolysis in Myocardial Infarction (TIMI)-2 trial also raises the possibility that such therapy may reduce the rate of intracranial hemorrhage (ICH). We reviewed data obtained from 60,329 patients treated with t-PA who were enrolled in the National Registry of Myocardial Infarction 2. Of the 60,329 in the study cohort, 23,749 patients (39.4%) were treated with immediate beta-blocker therapy and 542 patients (0.9%) developed an ICH. In a multivariate model that included all covariates known to be associated with the development of ICH, immediate beta-blocker therapy was associated with a 31% reduction in the ICH rate (odds ratio 0.69, 95% confidence intervals 0.57 to 0.84). Thus, in the present study, the use of immediate beta-blocker therapy in patients with AMI treated with t-PA was associated with a significant reduction in ICH. This finding supports the observations made in the TIMI 2 trial and serves to reinforce the recommendations made by the American College of Cardiology/American Heart Association task force that immediate beta-blocker therapy should be administered to all patients with AMI who do not have contraindications to this therapy.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Hemorragias Intracraneales/prevención & control , Infarto del Miocardio/tratamiento farmacológico , Activadores Plasminogénicos/efectos adversos , Terapia Trombolítica , Activador de Tejido Plasminógeno/efectos adversos , Anciano , California , Estudios de Cohortes , Femenino , Humanos , Hemorragias Intracraneales/tratamiento farmacológico , Masculino , Massachusetts , Michigan , Sistema de Registros , Estudios Retrospectivos
4.
Int J Obes Relat Metab Disord ; 24(2): 232-5, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10702776

RESUMEN

OBJECTIVE: To study whether body mass index (BMI) is different in girls with Turner syndrome (TS) compared to normal girls, and whether BMI in TS is affected by growth hormone (GH) treatment. DESIGN: A retrospective cross-sectional study. SUBJECTS: 2468 girls with TS enrolled in the National Cooperative Group Study (NCGS), a collaborative surveillance study for assessing GH-treated children. MEASUREMENTS: BMI and BMI standard deviation score (BMI SDS) at baseline and during GH treatment were computed from height and weight data. RESULTS: BMI in TS patients increases with age as expected. However, BMI SDS increased starting at about age 9 y. A similar pattern of increase in BMI SDS was observed after each year of GH treatment for up to 4 y, but GH treatment did not change the magnitude of increase. BMI and BMI SDS curves before and during GH treatment were essentially superimposable. CONCLUSION: These findings suggest that mechanisms specific for TS are responsible for the age-related increase in BMI SDS. This increase was unaffected by GH treatment.


Asunto(s)
Índice de Masa Corporal , Hormona de Crecimiento Humana/uso terapéutico , Obesidad/metabolismo , Síndrome de Turner/metabolismo , Adolescente , Factores de Edad , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Estudios Retrospectivos , Síndrome de Turner/tratamiento farmacológico
5.
Ann Intern Med ; 129(9): 690-7, 1998 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-9841600

RESUMEN

BACKGROUND: Left bundle-branch block (BBB) is considered an important predictor of poor outcome in patients with acute myocardial infarction, but the consequences of right BBB are not well understood. OBJECTIVES: To 1) estimate the prevalence of left and right BBB in patients with myocardial infarction; 2) compare the clinical characteristics of and treatments received by patients with left, right, or no BBB; and 3) determine the independent association of left BBB and right BBB with in-hospital death. DESIGN: Retrospective cohort study. SETTING: Multicenter registry of 1571 U.S. hospitals. PATIENTS: 297,832 patients with acute myocardial infarction who had left, right, or no BBB on initial electrocardiography. MEASUREMENTS: Presence and type of BBB, clinical characteristics of patients, therapies given, and in-hospital death. RESULTS: Patients with left BBB (n = 19,967; 6.7%) or right BBB (n = 18,354; 6.2%) were older and had more comorbid illness and congestive heart failure than patients with no BBB. Among patients for whom thrombolytic therapy was clearly indicated, fewer patients with left or right BBB (16.6% and 32.0%, respectively) than patients with no BBB (66.5%) received this therapy (P < 0.001). Fewer patients with left or right BBB (60.6% and 67.3%, respectively) than patients with no BBB (75.6%) received aspirin within the first 24 hours (P < 0.001), and fewer patients with left or right BBB (23.9% and 31.8%, respectively) than patients with no BBB (40.4%) received beta-blockers within the first 24 hours (P < 0.001). Unadjusted in-hospital mortality rates were almost twice as high for patients with left or right BBB (22.6% and 23.0%, respectively) as for patients with no BBB (13.1%) (P < 0.001). Compared with no BBB and no ST-segment elevation, left BBB was associated with a 34% increase (odds ratio, 1.34 [95% CI, 1.28 to 1.39]) and right BBB was associated with a 64% increase (odds ratio, 1.64 [CI, 1.57 to 1.71]) in the risk for in-hospital death, after adjustment for potential confounders. CONCLUSIONS: In patients with acute myocardial infarction, prevalences of right and left BBB are similar. Patients with BBB have more comorbid conditions, are less likely to receive therapy, and have an increased risk for in-hospital death compared with patients with no BBB. Compared with left BBB, right BBB seems to be a stronger independent predictor of in-hospital death.


Asunto(s)
Bloqueo de Rama/mortalidad , Mortalidad Hospitalaria , Infarto del Miocardio/mortalidad , Bloqueo de Rama/complicaciones , Bloqueo de Rama/tratamiento farmacológico , Dolor en el Pecho/etiología , Estudios de Cohortes , Comorbilidad , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Estadística como Asunto , Terapia Trombolítica
6.
Horm Metab Res ; 30(9): 565-9, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9808325

RESUMEN

We used the Genentech National Cooperative Growth Study database to examine differences in weight relative to height (weight for height standard deviation score or WTHTZ) in 3460 patients at enrollment and after one year of therapy with recombinant human growth hormone (rhGH), and in a subset of 450 patients treated for three years with rhGH. The major diagnostic categories were idiopathic growth hormone deficiency (IGHD), organic GH deficiency (OGHD), and idiopathic short stature (ISS). Children with IGHD and ISS were underweight for height at baseline but had a progressive increase in WTHTZ during three years of rhGH therapy. The same pattern applied to children with IGHD associated with septo-optic dysplasia and CNS trauma or infection. However, children with OGHD associated with craniopharyngiomas, other CNS tumors, leukemia, or CNS irradiation were overweight when starting rhGH and showed a decrease in WTHTZ during the first year of rhGH therapy. The increase in WTHTZ during rhGH treatment in children with ISS and OGHD suggests that the GH-induced increase in muscle mass exceeded loss of fat mass. Because children with neoplasm-related OGHD were overweight at baseline, the decline in WTHTZ during the first year of rhGH therapy suggests that loss of fat mass is the predominant effect in this subgroup.


Asunto(s)
Estatura/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Desarrollo Infantil , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Niño , Craneofaringioma/complicaciones , Trastornos del Crecimiento/etiología , Humanos , Estudios Longitudinales , Neoplasias Hipofisarias/complicaciones , Proteínas Recombinantes/administración & dosificación
7.
Ann Intern Med ; 129(8): 597-604, 1998 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-9786806

RESUMEN

BACKGROUND: The efficacy of thrombolytic therapy in reducing mortality from acute myocardial infarction has been unequivocally shown. However, thrombolysis is related to bleeding complications, including intracranial hemorrhage. OBJECTIVE: To determine the frequency of and risk factors for intracranial hemorrhage after recombinant tissue-type plasminogen activator (tPA) given for acute myocardial infarction in patients receiving usual care. DESIGN: Large national registry of patients who have had acute myocardial infarction. SETTING: 1484 U.S. hospitals. PATIENTS: 71073 patients who had had acute myocardial infarction from 1 June 1994 to 30 September 1996, received tPA as the initial reperfusion strategy, and did not receive a second dose of any thrombolytic agent. MEASUREMENT: Intracranial hemorrhage confirmed by computed tomography or magnetic resonance imaging. RESULTS: 673 patients (0.95%) were reported to have had intracranial hemorrhage during hospitalization for acute myocardial infarction; 625 patients (0.88%) had the event confirmed by computed tomography or magnetic resonance imaging. Of the 625 patients with confirmed intracranial hemorrhage, 331 (53%) died during hospitalization. An additional 158 patients (25.3%) who survived to hospital discharge had residual neurologic deficit. In multivariable models for the main effects of candidate risk factors, older age, female sex, black ethnicity, systolic blood pressure of 140 mm Hg or more, diastolic blood pressure of 100 mm Hg or more, history of stroke, tPA dose more than 1.5 mg/kg, and lower body weight were significantly associated with intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage is a rare but serious complication of tPA in patients with acute myocardial infarction. Appropriate drug dosing may reduce the risk for this complication. Other therapies, such as primary coronary angioplasty, may be preferable in patients with acute myocardial infarction who have a history of stroke.


Asunto(s)
Hemorragia Cerebral/inducido químicamente , Infarto del Miocardio/terapia , Terapia Trombolítica , Activador de Tejido Plasminógeno/efectos adversos , Factores de Edad , Anciano , Hemorragia Cerebral/diagnóstico , Trastornos Cerebrovasculares/complicaciones , Femenino , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Factores de Riesgo , Tomografía Computarizada por Rayos X
8.
J Pediatr Endocrinol Metab ; 11(3): 403-12, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-11517956

RESUMEN

Over a 9-year period (1985-1994) approximately 20,000 children received recombinant human growth hormone (rhGH) while enrolled in the National Cooperative Growth Study (NCGS), an observational, longitudinal study designed to monitor the long term efficacy and safety of rhGH administered to children in North America. Forty-four percent of the patients had idiopathic growth hormone deficiency (IGHD), 13.8% organic GHD (OGHD), 25% idiopathic short stature (ISS), 9.9% Turner's syndrome (TS), and 7.3% miscellaneous disorders. Eighty-five percent of the patients enrolled were Caucasian, and approximately two-thirds of the non-Turner patients were male. For the subset of patients treated for at least 4 years and who were prepubertal throughout this period (IGHD N=308, OGHD N=93, ISS N=169, TS N=82), mean growth rates increased in all patient categories and remained at or above pretreatment growth rates through 4 consecutive years of therapy with rhGH. Growth rates during administration of rhGH were greater in children in whom the pretreatment maximum stimulated GH concentration was < or =3 microg/l. Patients treated with 6 or 7 doses of rhGH each week grew more rapidly than did those receiving thrice weekly dosages, although the ratios of the increment in bone age to the increment in height age after two years of therapy were similar in the two treatment regimens. For patients treated with rhGH for 7 consecutive years, the mean height standard deviation scores increased by 2.5 in IGHD (N=169), 2.0 in OGHD (N=50), 1.9 in ISS (N=69), and 1.3 in TS (N=19), but remained below target heights in all categories. It is concluded that administration of rhGH increases growth rates in patients with IGHD, OGHD, ISS, and TS, and that this stimulatory effect can persist for at least 4 years.


Asunto(s)
Hormona de Crecimiento Humana/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Adolescente , Estatura/efectos de los fármacos , Niño , Esquema de Medicación , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/deficiencia , Humanos , Inyecciones , Estudios Longitudinales , Masculino , Concentración Osmolar , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Síndrome de Turner/tratamiento farmacológico
9.
J Pediatr ; 131(1 Pt 2): S32-6, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9255225

RESUMEN

BACKGROUND: Data have suggested that any increased incidence of leukemia in growth-hormone (GH)-treated patients was limited to those with known risk factors for leukemia. However, previous studies may have overestimated the numbers of patient-years of risk by not excluding data from "positive-risk-factor" patients. This risk was reanalyzed by using data on children in the National Cooperative Growth Study (NCGS), with correction for this possible confounding factor. METHODS: The risk of leukemia in GH-treated patients without known risk factors was determined by using patient-years of GH therapy and patient-years since first exposure to GH therapy and the values obtained were compared with values from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. RESULTS: Three cases of leukemia in patients without known risk factors were found in the NCGS database; 3.42 cases would be expected in the 119,846 patient-years in the analysis using time since GH exposure. Two of these cases of leukemia occurred during GH therapy (67,773 patient-years); 2.13 cases would be expected. CONCLUSION: Excluding data on patients with known risk factors for leukemia provides a more accurate estimate of the risks in GH-treated patients. The incidence of leukemia in these patients is comparable to that in the general population of age-matched children.


Asunto(s)
Hormona de Crecimiento Humana/efectos adversos , Leucemia/inducido químicamente , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Factores de Confusión Epidemiológicos , Femenino , Humanos , Incidencia , Sistemas de Información , Masculino , National Institutes of Health (U.S.) , Factores de Riesgo , Programa de VERF , Factores de Tiempo , Estados Unidos
10.
J Pediatr ; 131(1 Pt 2): S56-60, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9255230

RESUMEN

OBJECTIVE: To assess the clinical utility of growth-hormone-binding protein (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3), levels in the evaluation of short stature. STUDY DESIGN: Prospective substudy of the National Cooperative Growth Study, a multicenter observational study. RESULTS: A total of 6447 assessable subjects undergoing workup for short stature were enrolled at 197 sites. At baseline the cause of short stature was undefined in 77% of subjects. Mean GHBP levels were lowest in subjects with renal disease and highest in those with Turner syndrome. No cases of complete GH insensitivity syndrome (Laron syndrome) were identified. Subjects with low GHBP levels were among those tested for GH receptor mutations. IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were positively correlated; both increased during GH therapy. There was a weak positive correlation between log peak GH levels and both IGF-I SDS and IGFBP-3 SDS and a weak negative correlation between log peak GH levels and GHBP SDS. Mean changes in GHBP SDS in subjects treated with GH and untreated subjects were not significant. Change in height SDS in subjects treated with GH was negatively correlated with age and IGF-I level but not correlated with baseline GHBP SDS. CONCLUSION: GHBP levels are GH independent and not predictive of responses to GH therapy, although low GHBP levels may indicate GH receptor abnormalities and partial GH insensitivity.


Asunto(s)
Proteínas Portadoras/sangre , Trastornos del Crecimiento/sangre , Hormona de Crecimiento Humana/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factores de Edad , Estatura/efectos de los fármacos , Canadá , Niño , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Predicción , Crecimiento/efectos de los fármacos , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/genética , Hormona de Crecimiento Humana/genética , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Enfermedades Renales/sangre , Masculino , Mutación/genética , Estudios Prospectivos , Receptores de Somatotropina/genética , Síndrome , Síndrome de Turner/sangre , Estados Unidos
11.
J Pediatr ; 128(5 Pt 2): S4-7, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8627468

RESUMEN

As of October 1993 the National Cooperative Growth Study included 1262 children with brain tumor who were treated with growth hormone. The type of brain tumor was specified in 947 (75%) of these children. The most common types were glioma, medulloblastoma, and craniopharyngioma, accounting for 91.3% of all those for which type was specified. Brain tumor recurred in 83 (6.6%) of the 1262 children over a total of 6115 patient-years at risk. The frequencies of tumor recurrence in children with low-grade glioma (18.1%), medulloblastoma (7.2%), and craniopharyngioma (6.4%) are lower than those in published reports of tumor recurrence in the general pediatric population with the same types of tumors. The analysis cannot conclusively show that no increased risk of tumor recurrence exists, however, because of the potential incompleteness of data reporting in the National Cooperative Growth Study. Nevertheless the findings are reassuring that children with the more common types of brain tumor who are treated with growth hormone do not seem to be at excessive risk for tumor recurrence.


Asunto(s)
Neoplasias Encefálicas/epidemiología , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/efectos adversos , Hormona del Crecimiento/uso terapéutico , Recurrencia Local de Neoplasia/epidemiología , Sistemas de Registro de Reacción Adversa a Medicamentos , Neoplasias Encefálicas/diagnóstico , Niño , Preescolar , Bases de Datos Factuales , Trastornos del Crecimiento/etiología , Humanos , Factores de Riesgo , Tasa de Supervivencia
12.
Horm Res ; 46(3): 113-6, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8894665

RESUMEN

We examined the association between slipped capital femoral epiphysis (SCFE) and growth hormone (GH) treatment in 16,514 children who had not been treated with GH prior to their enrollment in the National Cooperative Growth Study. Fifteen children had SCFE prior to receiving GH therapy, 26 developed SCFE during GH treatment, and one had SCFE on one side prior to GH treatment and developed it on the contralateral side while receiving GH. Children with GH deficiency were significantly more likely to develop SCFE while on GH treatment than were children with idiopathic short stature (p = 0.006). There was no difference between GH-deficient girls and boys in the risk of developing SCFE during GH treatment. There were 3 cases of SCFE in girls with Turner syndrome before GH treatment and 3 during. Typically, children who developed SCFE while on GH were older, heavier, and grew more slowly during the first year of GH than those who did not. Children with GH deficiency, Turner syndrome, and other known causes of short stature are more likely to develop SCFE before or during GH treatment than children with idiopathic short stature.


Asunto(s)
Epífisis Desprendida/etiología , Fémur , Hormona de Crecimiento Humana/efectos adversos , Adolescente , Niño , Femenino , Trastornos del Crecimiento/complicaciones , Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/deficiencia , Humanos , Masculino , Factores de Riesgo , Síndrome de Turner/complicaciones , Síndrome de Turner/tratamiento farmacológico
13.
N Engl J Med ; 333(17): 1093-8, 1995 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-7565946

RESUMEN

BACKGROUND: Short stature in children who are not deficient in growth hormone (GH) is probably caused by a variety of defects. Some children with idiopathic short stature have low serum concentrations of GH-binding protein, which is derived from the GH receptor. The possibility that low serum concentrations of GH-binding protein might indicate partial insensitivity to GH led us to investigate possible defects in the gene for the GH receptor in children with idiopathic short stature and low serum concentrations of GH-binding protein. METHODS: We studied 14 children with idiopathic short stature who were selected on the basis of normal GH secretion and low serum concentrations of GH-binding protein. Analysis of single-strand conformation polymorphisms and DNA sequencing were both used to identify mutations in the GH-receptor gene. RESULTS: Mutations in the region of the GH-receptor gene that codes for the extracellular domain of the receptor were found in 4 of the 14 children, but in none of 24 normal subjects. One of the four children with mutations was a compound heterozygote, with one mutation that reduced the affinity of the receptor for GH and a second mutation that may affect a function other than ligand binding. The remaining three children had single mutations in one allele of the gene. One mutation introduced a premature termination codon, and two caused substitutions of single amino acids in a structurally conserved domain of the receptor. CONCLUSIONS: Some children with idiopathic short stature may have partial insensitivity to GH due to mutations in the GH-receptor gene.


Asunto(s)
Proteínas Portadoras/sangre , Trastornos del Crecimiento/genética , Mutación , Receptores de Somatotropina/genética , Adolescente , Proteínas Portadoras/química , Niño , Preescolar , Exones/genética , Femenino , Trastornos del Crecimiento/sangre , Hormona del Crecimiento/química , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Linaje , Polimorfismo Genético , Estructura Terciaria de Proteína , Receptores de Somatotropina/análisis , Receptores de Somatotropina/química , Análisis de Secuencia de ADN
14.
J Pediatr ; 127(2): 244-50, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7636649

RESUMEN

OBJECTIVE: To determine whether some patients with idiopathic short stature have partial resistance to growth hormone (GH). Patients with idiopathic short stature have decreased serum levels of the GH receptor-related GH-binding protein (GHBP), and low GHBP levels are associated with complete GH insensitivity (Laron) syndrome. We hypothesized that patients with idiopathic short stature and low GHBP levels may also have a degree of GH insensitivity. DESIGN: Retrospective analysis of patients in a multicenter study. SETTING: Ninety-six National Cooperative Growth Study centers in the United States and Canada. SUBJECTS: Five hundred eleven patients with idiopathic short stature who were treated with GH. All patients had a baseline height standard deviation score of less than -2 and a maximum stimulated GH level greater than 10 micrograms/L. Of these, 101 (20%) had a baseline GHBP standard deviation score of -2 or less. RESULTS: The patients with low GHBP levels, in comparison with those with normal GHBP levels, had a lower mean extracted standard deviation score for insulin-like growth factor I (-3.3 +/- 1.1 vs -2.5 +/- 1.4; p < 0.0001) but mean 12-hour GH values (2.8 +/- 1.1 vs 2.3 +/- 1.1 micrograms/L; p <0.0001). The differences between groups were statistically significant after control for age and weight-for-height standard deviation score. Among prepubertal patients, there was no significant difference between the low and normal GHBP groups in mean pretreatment or first-year growth rate (p = 0.74, 0.61 respectively) with comparable doses of GH. CONCLUSIONS: Patients with idiopathic short stature and low GHBP levels, compared with those with normal GHBP levels, had significantly lower standardized levels of insulin-like growth factor I, and higher mean 12-hour GH levels, which suggest partial GH insensitivity. There was no significant correlation of GHBP levels with the growth response to exogenous GH.


Asunto(s)
Proteínas Portadoras/sangre , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Estatura/efectos de los fármacos , Estudios de Casos y Controles , Niño , Femenino , Trastornos del Crecimiento/sangre , Hormona del Crecimiento/sangre , Hormona del Crecimiento/deficiencia , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Modelos Lineales , Masculino , Valores de Referencia , Estudios Retrospectivos
15.
J Clin Endocrinol Metab ; 80(4): 1416-22, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7714117

RESUMEN

This report describes cases of new extracranial nonleukemic neoplasms in recombinant human GH (rhGH) recipients. The data are largely from the National Cooperative Growth Study (NCGS), with over 51,000 patient-years at risk from 12,209 patients treated with Protropin rhGH. In addition to case reports of extracranial tumors from the NCGS enrollees, there have been reports from non-NCGS patients. Ten cases of new extracranial neoplasms have been reported from this total study population, and there have been eight cases whose second neoplasms were extracranial in nature. For the new cases, the number of observed cases is compared with the number of expected cases, as derived from incidence rates published by the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Program. The standard morbidity ratio (SMR), defined as the number of observed cases/expected cases, is calculated for males and females separately, with further subgroup analysis based upon age. For the NCGS population, the SMRs were not statistically distinguishable from unity (i.e. 1). When the number of non-NCGS Protropin patients is estimated and SMRs are calculated for the total Protropin-treated group, the SMRs remain statistically indistinguishable from one. At present, these data suggest that rhGH does not increase the risk for developing nonleukemic extracranial neoplasms. Because a small number of additional cases could significantly alter the SMR calculations, meticulous reporting and continued surveillance must continue.


Asunto(s)
Hormona del Crecimiento/uso terapéutico , Neoplasias/epidemiología , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Recurrencia Local de Neoplasia/epidemiología , Neoplasias/complicaciones , Proteínas Recombinantes , Factores de Riesgo , Factores Sexuales , Síndrome de Turner/complicaciones , Población Blanca
16.
Psychother Psychosom ; 62(3-4): 193-9, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7846263

RESUMEN

Quality of life was assessed in 57 patients with limited small-cell carcinoma of the lung utilizing psychological scales that measured mood, functional status, and cognitive impairment. These patients received chemotherapy with or without radiotherapy to the primary tumor. All patients received prophylactic cranial radiation. Patients who received the combination of chemotherapy and radiotherapy to both the primary tumor and CNS had an increase in overall survival. However, because of the increased toxicity experienced by these patients, a decrease in quality of life was documented by measures of psychological distress when compared to patients receiving chemotherapy alone. The findings support the importance of utilizing quality of life measures in addition to measures of physical toxicity so that patients can make an informed choice regarding treatment options.


Asunto(s)
Carcinoma de Células Pequeñas/psicología , Neoplasias Pulmonares/psicología , Calidad de Vida , Rol del Enfermo , Actividades Cotidianas/psicología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Irradiación Craneana/psicología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Determinación de la Personalidad , Dosificación Radioterapéutica , Radioterapia Adyuvante
17.
J Bone Miner Res ; 7(4): 449-56, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1535172

RESUMEN

Among 2992 white women aged 65-70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5-L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity greater than or equal to 4 SD. Vertebral deformities less than 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was greater than or equal to 4 SD had a 1.9 (95% CI, 1.5-2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7-3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0-3.2) times more likely to have lost greater than or equal to 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities less than 4 SD did not increase the likelihood of these three outcomes, but multiple deformities greater than or equal to 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.


Asunto(s)
Dolor de Espalda/etiología , Personas con Discapacidad , Osteoporosis Posmenopáusica/complicaciones , Enfermedades de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/etiología , Anciano , Dolor de Espalda/diagnóstico por imagen , Estatura/fisiología , Femenino , Humanos , Dimensión del Dolor/métodos , Prevalencia , Radiografía , Factores de Riesgo , Enfermedades de la Columna Vertebral/diagnóstico por imagen
18.
J Clin Oncol ; 9(12): 2219-24, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1960562

RESUMEN

Two hundred ninety patients with a recent diagnosis of multiple myeloma were studied psychologically at the time of initial treatment. Physician- and patient-completed psychosocial scales were correlated with physical variables used to measure tumor load and physical status. A logistic regression model was used to analyze objective response to treatment. Indirect measures of response to treatment were obtained, and factors influencing survival duration were studied using a Cox regression model. If physical variables were controlled, there were no significant correlations between psychologic scores on entry and response to treatment or survival duration. Thus, the notion that mood influences disease outcome once the disease process has begun in patients with multiple myeloma is not supported by this data set.


Asunto(s)
Afecto , Mieloma Múltiple/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Análisis de Supervivencia , Resultado del Tratamiento
19.
JAMA ; 266(12): 1657-63, 1991 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-1886188

RESUMEN

OBJECTIVE: --To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN: --Cross-sectional survey. SETTING: --Kigali, Rwanda. PARTICIPANTS: --A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE: --Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS: --The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS: --The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.


Asunto(s)
Seroprevalencia de VIH , Complicaciones Infecciosas del Embarazo/epidemiología , Conducta Sexual/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Anticuerpos Anti-VIH/análisis , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Humanos , Incidencia , Masculino , Matrimonio , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Prevalencia , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Rwanda/epidemiología , Factores Socioeconómicos , Población Urbana
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