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1.
Cancer Res ; 54(18): 4999-5004, 1994 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-8069867

RESUMO

We report the establishment of a leukemia cell line (UoC-B10) from a patient who developed leukemia several months after the diagnosis of a mediastinal yolk sac tumor. The patient's yolk sac tumor responded to combination chemotherapy, and a mature teratoma with focal areas of hematopoiesis was subsequently resected. However, 5 months after the initial diagnosis, the patient developed an acute lymphoblastic leukemia with a precursor B-cell phenotype. Cytogenetic analysis showed an i(12p) abnormality in the patient's leukemia cells and in the UoC-B10 cell line. The i(12p) was also identified retrospectively in the mediastinal tumor cells by fluorescent in situ hybridization analysis. The UoC-B10 cell line, which has been growing continuously for > 24 months in culture, was Epstein-Barr virus negative and was generally concordant with the patient's leukemia cells by analysis of immunophenotype, karyotype, and genotype. The UoC-B10 cell line possesses receptors for granulocyte-colony-stimulating factor, a cytokine which the patient received as part of his treatment protocol. This cell line may be useful in studying the relationship between i(12p) and hematological differentiation of human mediastinal germ cell tumors.


Assuntos
Cromossomos Humanos Par 12 , Cromossomos Humanos Par 13 , Tumor do Seio Endodérmico/complicações , Leucemia de Células B/genética , Neoplasias do Mediastino/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adulto , Biomarcadores Tumorais , Tumor do Seio Endodérmico/tratamento farmacológico , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Imunofenotipagem , Cariotipagem , Leucemia de Células B/enzimologia , Leucemia de Células B/patologia , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptores de Fator Estimulador de Colônias de Granulócitos/análise , Células Tumorais Cultivadas
2.
J Med Genet ; 41(9): 669-78, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15342697

RESUMO

INTRODUCTION: Array comparative genomic hybridisation (array CGH) is a powerful method that detects alteration of gene copy number with greater resolution and efficiency than traditional methods. However, its ability to detect disease causing duplications in constitutional genomic DNA has not been shown. We developed an array CGH assay for X linked hypopituitarism, which is associated with duplication of Xq26-q27. METHODS: We generated custom BAC/PAC arrays that spanned the 7.3 Mb critical region at Xq26.1-q27.3, and used them to search for duplications in three previously uncharacterised families with X linked hypopituitarism. RESULTS: Validation experiments clearly identified Xq26-q27 duplications that we had previously mapped by fluorescence in situ hybridisation. Array CGH analysis of novel XH families identified three different Xq26-q27 duplications, which together refine the critical region to a 3.9 Mb interval at Xq27.2-q27.3. Expression analysis of six orthologous mouse genes from this region revealed that the transcription factor Sox3 is expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. DISCUSSION: Array CGH is a robust and sensitive method for identifying X chromosome duplications. The existence of different, overlapping Xq duplications in five kindreds indicates that X linked hypopituitarism is caused by increased gene dosage. Interestingly, all X linked hypopituitarism duplications contain SOX3. As mutation of this gene in human beings and mice results in hypopituitarism, we hypothesise that increased dosage of Sox3 causes perturbation of pituitary and hypothalamic development and may be the causative mechanism for X linked hypopituitarism.


Assuntos
Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Duplicação Gênica , Genes Duplicados/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas de Grupo de Alta Mobilidade/genética , Hipopituitarismo/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ligação Genética/genética , Genoma Humano , Humanos , Hipotálamo/embriologia , Hipotálamo/metabolismo , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Camundongos , Hibridização de Ácido Nucleico , Linhagem , Hipófise/embriologia , Hipófise/metabolismo , Reprodutibilidade dos Testes , Fatores de Transcrição SOXB1
3.
Endocrinology ; 133(2): 505-10, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8344196

RESUMO

Recent studies have shown that the basal release of PRL from anterior pituitary cells is inhibited by endothelin-1 (ET-1) and ET-3. To determine whether ET also regulates the synthesis and release of PRL by decidual cells, we examined the effects of ET on the synthesis and release of PRL from an enriched fraction of human decidual cells prepared by isopycnic centrifugation of enzymatically dispersed term decidual tissue. Exposure of decidual cells to ET-1 (10(-7) M) for 96 h caused a progressive decrease in basal PRL synthesis and release beginning 24 h after exposure with half-maximal inhibition occurring at an ET-1 concentration of 5 x 10(-9) M. Between 72-96 h of culture, ET-1-exposed cells synthesized 37.2 +/- 2.7% (SEM) and released 32.3 +/- 1.3% less PRL than control cells (P < 0.01). ET-1-exposed cells incubated with [35S]methionine between 72-96 h also released less [35S] PRL than control cells. Sarafotoxin S6C, an ETB receptor agonist, also inhibited basal PRL release, whereas BQ-123, an ETA receptor antagonist, had no effect on basal or on ET-1-mediated inhibition of PRL release. ET-1 also markedly inhibited the stimulation of PRL synthesis and release in response to insulin and insulin-like growth factor-1 (IGF-1). Cells exposed to insulin (100 ng/ml) and IGF-1 (50 ng/ml) alone released 61.2 +/- 3.6% and 40.0 +/- 3.8% more PRL, respectively, than control cells between 72-96 h of exposure. However, cells exposed simultaneously to insulin and ET-1 (10(-7) M) released only 17.1 +/- 3.5% more PRL than control cells during the same time period, and cells exposed simultaneously to IGF-1 and ET-1 released only 4.1 +/- 1.8% more PRL than controls during the same time interval (P vs. insulin or IGF-1 alone < 0.001 in each instance). Both basal and insulin- and IGF-1-stimulated PRL release were also inhibited by the ET isotypes ET-2 and ET-3, and by the ET-1 precursor, big ET. Since macrophages and decidual cells synthesize ET, and decidual tissue contains specific receptors for ET, the inhibitory action of ET on basal and stimulated PRL release may result from an autocrine and/or paracrine effect and appears to be mediated through the ETB receptor.


Assuntos
Decídua/metabolismo , Endotelinas/farmacologia , Prolactina/metabolismo , Células Cultivadas , Decídua/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotelinas/administração & dosagem , Feminino , Humanos , Insulina/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia
4.
Endocrinology ; 133(4): 1525-31, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7691578

RESUMO

Previous studies demonstrated that human decidual cells release insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-2, and a 24-kilodalton (kDa) IGFBP in culture. The accumulation of 24-kDa IGFBP, as assessed by ligand blot analysis, decreased when the cells were exposed to IGF-I, but the mechanism was not explored. In the present study, we observed that the IGF-I-mediated decrease in IGFBP-4 accumulation could be explained by increased IGFBP-4 proteolysis. Analysis by IGFBP-4 immunoblotting demonstrated a decline in 24-kDa IGFBP-4 accompanied by a marked increase in a 17- to 18.5-kDa IGFBP-4 fragment(s). In addition, when medium from IGF-I-treated cells was incubated with rat IGFBP-4, the decrease in IGFBP-4 was inhibited by chelators of divalent cations and inhibitors of serine proteases. IGF-I enhancement of IGFBP-4 proteolysis occurs independent of the type I IGF receptor. [Leu24,1-62]IGF-I, an analog with reduced receptor affinity, mimicked the effect of native IGF-I in cell culture. Additionally, alpha-IR3, a monoclonal antibody to the type I IGF receptor, did not block the effect of IGF-I. When IGF-I was incubated with medium from control cells, there was a marked decrease in 24-kDa IGFBP-4 levels and a concomitant increase in levels of a 17- to 18.5-kDa fragment(s), suggesting that IGFBP-4 complexed with IGF-I is more susceptible to proteolysis than IGFBP-4 alone. Together, these findings suggest a novel mechanism for regulation of IGF-I action in the decidua.


Assuntos
Proteínas de Transporte/metabolismo , Decídua/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Peptídeo Hidrolases/metabolismo , Receptores de Somatomedina/metabolismo , Células Cultivadas , Meios de Cultivo Condicionados , Decídua/citologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Immunoblotting , Insulina/farmacologia , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Somatomedinas/metabolismo
5.
Bone Marrow Transplant ; 13(3): 341-4, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8199578

RESUMO

Guillain-Barré syndrome appeared in two patients following autologous bone marrow transplantation for metastatic breast cancer. In one case, the patient responded to plasmapheresis and became ambulatory. In the second case, the patient died of an unrelated complication: intracerebral hemorrhage. Although Guillain-Barré syndrome is associated with hematologic malignancies, it has not been previously reported in patients with solid tumors undergoing autologous bone marrow transplantation. Because both patients were in remission at the time of the autograft, Guillain-Barré syndrome may emerge as a rare complication of altered immune function and/or viral infection after marrow transplantation.


Assuntos
Adenocarcinoma/terapia , Transplante de Medula Óssea/efeitos adversos , Neoplasias da Mama/terapia , Polirradiculoneuropatia/etiologia , Adenocarcinoma/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Sistema Imunitário/fisiologia , Pessoa de Meia-Idade , Plasmaferese , Polirradiculoneuropatia/terapia , Transplante Autólogo , Viroses/complicações
6.
Bone Marrow Transplant ; 13(4): 449-54, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8019470

RESUMO

This retrospective analysis was done to determine the response rate and survival of women with metastatic breast cancer with bone marrow involvement treated with high-dose cyclophosphamide and thiotepa and peripheral progenitor cell rescue. Eligibility criteria included histologically-documented metastatic breast cancer and either stable disease, a partial response or a complete response to conventional dose chemotherapy. Due to bone marrow involvement, all patients received peripheral progenitor cell reinfusion. Purging of the stem cell product was not performed. Cyclophosphamide (CY) 7.5 gm/m2 total dose and thiotepa 675 mg/m2 total dose was used as the intensification regimen. Of 27 treated patients, 4 (14%) died of treatment-related toxicity. Three patients were in complete remission after induction chemotherapy and remained so after high-dose chemotherapy. Three patients converted from a partial response after induction to a complete response after transplant. This yielded a complete remission rate of 21%. Five of these six patients continue in CR at 5, 6, 11, 14, and 26 months post-transplant. Eight patients (29%) are alive with stable disease post transplant. Ten patients developed disease progression. Six patients died shortly after disease progression; however, four patients are alive with disease at 18, 26, 33, and 53 months post-transplant. The median time to treatment failure is 12 months. In women with metastatic breast cancer with bone marrow involvement, durable responses after high-dose chemotherapy are possible utilizing peripheral blood progenitor support rather than marrow purging.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Componentes Sanguíneos , Transfusão de Sangue Autóloga , Neoplasias da Mama/tratamento farmacológico , Células-Tronco Hematopoéticas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Pancitopenia/induzido quimicamente , Pancitopenia/terapia , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Falha de Tratamento
7.
Hematol Oncol Clin North Am ; 7(3): 631-45, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8102137

RESUMO

Patients with metastatic breast cancer with chemotherapy-sensitive disease, good performance status, and few sites of metastatic disease are the best candidates for high-dose chemotherapy and autologous stem cell reinfusion. Even in this selected subset of patients with metastatic breast cancer, at best 30% to 40% will maintain a complete remission beyond 2 years. In the high-risk adjuvant setting, high-dose chemotherapy appears efficacious; however, results from ongoing randomized prospective trials will not be available for several years.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores de Risco , Transplante Autólogo
8.
Leuk Lymphoma ; 8(3): 229-33, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1490149

RESUMO

Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.


Assuntos
Anfotericina B/uso terapêutico , Aspergilose/prevenção & controle , Pneumopatias Fúngicas/prevenção & controle , Neutropenia/complicações , Infecções Oportunistas/prevenção & controle , Adulto , Aerossóis , Anfotericina B/administração & dosagem , Aspergilose/epidemiologia , Transplante de Medula Óssea , Feminino , Humanos , Hospedeiro Imunocomprometido , Incidência , Leucemia/complicações , Leucemia/tratamento farmacológico , Pneumopatias Fúngicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Projetos Piloto
9.
J Pediatr Endocrinol Metab ; 14(8): 1097-105, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11592566

RESUMO

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH) deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy, and whether these effects on body composition are dose-dependent as seen in adult GH deficiency. OBJECTIVES AND METHODS: After 24 months of GH theapy at a dose of 1 mg/m2/day ("standard dose"), the effects of 12 additional months of GH treatment at varying doses (0.3-1.5 mg/m2/day) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 46 children with PWS. Percent body fat, lean muscle mass, and bone mineral density (BMD) were measured by dual X-ray absorptiometry (DXA). Indirect calorimetry was used to determine REE and to calculate respiratory quotient (RQ). RESULTS: During months 24-36 of GH therapy, further changes in body composition (decrease in fat mass, and increase in lean body mass), growth velocity, and REE occurred with standard and higher-dose GH therapy (1.5 mg/m2/day), but not with lower dose GH (0.3 mg/m2/day). Prior improvements in BMD, and strength and agility, which occurred during the initial 24 months, were sustained during the additional 12 months (to 36 months) regardless of dose. CONCLUSIONS: Salutary and sustained GH-induced changes in growth, body composition, and physical function in children with PWS require GH doses of >0.3 mg/m2/day. Conversely, BMD increased during the additional 12 months of therapy regardless of GH dose. Lower doses of GH, effective in improving body composition in adults with GHD, do not appear to be effective in children with PWS.


Assuntos
Composição Corporal , Crescimento , Hormônio do Crescimento Humano/uso terapêutico , Metabolismo dos Lipídeos , Aptidão Física , Síndrome de Prader-Willi/tratamento farmacológico , Absorciometria de Fóton , Tecido Adiposo , Adolescente , Fenômenos Biomecânicos , Estatura , Densidade Óssea , Calorimetria Indireta , Criança , Pré-Escolar , Metabolismo Energético , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Lipídeos/sangue , Pulmão/fisiopatologia , Masculino , Músculo Esquelético/fisiopatologia , Síndrome de Prader-Willi/fisiopatologia
10.
J Anim Sci ; 77(2): 300-10, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10100657

RESUMO

A 2-yr study was conducted to determine the effects of three weaning management systems on cow and steer performance. Cow-calf pairs were randomly assigned to one of three treatments, in which the steer calves were 1) early-weaned (yr 1, 177 +/- 9 d; yr 2, 158 +/- 21 d of age) and placed on a finishing diet (EW), 2) supplemented with grain for 55 d on pasture (yr 1, 177 to 231 d; yr 2, 158 to 213 d of age) while nursing their dams and then placed on a finishing diet (NWC), and 3) on pasture for 55 d while nursing their dams (yr 1, 177 to 231 d; yr 2, 158 to 213 d of age) and then placed on a finishing diet (NW). In yr 2, potential breed differences were evaluated using steers of three breed types: 1) Angus x Hereford (BRI); 2) Angus x Simmental (CON); and 3) Angus x Wagyu (WAG). In yr 1, EW steers gained 100% faster (P = .0001) than the average of NWC and NW steers, and NWC steers gained 32% faster (P = .02) than NW steers before weaning. In the feedlot, EW steers had lower intakes (7.70 vs 8.16 kg/d, P = .008) and better feed conversions (.170 vs .153, P = .002) than the average of NWC and NW steers. Marbling score was improved for EW steers compared with the average of NWC and NW steers (P = .003). In yr 2, EW steers had higher gains (P = .0006) during the entire study than the average of NWC and NW steers, and NWC steers had higher gains (P = .003) than NW steers. The EW steers had lower intakes (7.29 vs 7.68 kg/d, P = .0008) and better feed conversions (.160 vs .141, P = .0001) than the average of NWC and NW steers. The CON steers were heavier at slaughter than BRI steers (P = .01), and BRI steers were heavier than WAG steers (P =.0004). Early weaning improved the percentage of steers grading Average Choice or higher by 40%. The percentage of BRI steers grading Choice or greater was 21% higher and percentage of steers grading Average Choice or greater was 33% higher than CON. Cows with EW steers had higher ADG than cows with NW steers (.38 vs -.17 kg/d, P = .0001) before weaning. Cows with EW steers gained in body condition score (.23 vs .00, P = .04), and cows with NW steers did not change. Early weaning improved feed efficiency and quality grades of beef steers.


Assuntos
Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal , Bovinos/fisiologia , Desmame , Animais , Constituição Corporal , Feminino , Masculino , Taxa de Gravidez , Fatores de Tempo
11.
J Anim Sci ; 77(2): 323-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10100659

RESUMO

An experiment was conducted to compare three weaning ages on cow-calf performance and steer carcass traits. Crossbred steers (n = 168; 1/2 Simmental x 1/4 Angus x 1/4 Hereford) were randomly assigned to three treatments with eight pens per treatment: groups were 1) weaned at an average of 90 d of age (90 +/- 13 d) and placed in the feedlot, 2) weaned at an average of 152 d of age (152 +/- 13 d) and placed in the feedlot, and 3) weaned at an average of 215 d of age (215 +/- 13 d) and placed in the feedlot. The number of days steers were finished decreased by 55 and 38 d (linear, P = .0001) as weaning age increased when slaughtered at a constant fat end point (.81 cm). Weaning at an average of 90 and 152 d of age improved overall ADG by .15 and .07 kg/d, respectively, over weaning at an average of 215 d of age (linear, P = .005). Over the entire finishing period, intake increased (linear, P = .0006) and efficiency was poorer (linear, P = .004) as weaning age increased. Owing to differences in finishing days and intake, total concentrate consumed increased (linear, P = .03) as weaning age decreased. No differences (P > .21) were observed for carcass weight, longissimus muscle area, or yield grade. No differences (P > .19) were observed in marbling score or percentage of steers grading greater than or equal to Choice or Average Choice. Cow body condition score improved (linear, P = .0001) as weaning age decreased. Pregnancy rate improved 12 percentage units (linear, P = .15) for cows on the 90-d weaning treatment. In this study, early weaning improved gain and feed efficiency, but it increased total concentrate consumed.


Assuntos
Criação de Animais Domésticos/métodos , Cruzamento/métodos , Bovinos/crescimento & desenvolvimento , Desmame , Fatores Etários , Animais , Feminino , Carne , Gravidez
12.
J Anim Sci ; 77(2): 311-22, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10100658

RESUMO

A 2-yr study was conducted to evaluate 1) steers fed ad libitum high concentrate after weaning (CONC), or 2) steers grown on pasture for 82 d, followed by high-concentrate finishing (PAST), on the performance and carcass traits of 74 early-weaned (117 d of age) steers. Potential breed differences were evaluated using crossbred steers of three types: 1) 3/4 Angus x 1/4 Simmental (BRI), 2) 3/4 Simmental x 1/4 Angus (CON), and 3) 1/2 Wagyu x 1/4 Angus x 1/4 Simmental (WAG). Steers were randomly assigned within breed to the two treatments. There was no interactions (P > .10), so the data were pooled over years. The CONC steers had an ADG that was .17 kg/d higher (P = .0001), intake 1.09 kg/d lower (P = .0001), and gain:feed ratio .013 unit better (.190 vs .177, P = .008) than PAST steers overall. Growing treatment did not affect total concentrate consumed (P = .97). The BRI steers required 31 d less than did CON steers (P = .008), and 23 d less than WAG steers (P = .05) when fed to a constant fat end point (1.1 cm). The BRI steers exhibited an ADG .16 kg/d higher (P = .0003), tended (P = .07) to have an ADG intake .49 kg/d higher, and exhibited gain:feed .01 unit better (.189 vs 180) than WAG steers. When compared with CON steers, BRI steers consumed 310 kg less total concentrate (P = .0003). No differences (P > .38) were observed between growing treatments for carcass characteristics or sensory attributes except that CONC steers tended (P = .11) to improve percentage of steers grading Average Choice or higher by 47% over PAST steers. The WAG steers had a 76-unit higher marbling score (1,000 = Small00, 1,100 = Modest00) (P = .006) than BRI steers, resulting in 19% more (P = .09) steers grading > or = Choice and 82% more (P = .03) grading > or = Average Choice. Liver (P = .15) and rumen (P = .01) weights as a percentage of hot carcass weight were reduced for CONC steers. The CONC steers had higher gain, lower intake, better efficiency, reduced liver and rumen weights, and consumed the same amount of total concentrate when compared with PAST steers. The BRI steers had less finishing days and lower daily intake compared with CON steers. The WAG steers had more days finishing, lower gain, lower intake, more undesirable efficiencies, consumed the same amount of total concentrate, and improved quality grades compared with BRI steers.


Assuntos
Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal , Bovinos/crescimento & desenvolvimento , Desmame , Ração Animal , Animais , Peso Corporal , Masculino , Carne
13.
Clin Pediatr (Phila) ; 36(6): 321-6, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9196230

RESUMO

Among 145 patients treated with recombinant human growth hormone (GH), four developed sleep apnea (two obstructive, two mixed) associated with tonsillar and adenoidal hypertrophy in three. These four patients had no local risk factors predisposing to upper airway obstruction (i.e., frequent pharyngitis or sinusitis). Clinical and/or polysomnographic features of sleep apnea improved following cessation of GH therapy in one patient, and following tonsillectomy and adenoidectomy in all patients. The present observations indicate that, albeit rarely, obstructive and/or central sleep apnea may occur in children treated with GH. Polysomnography should be considered if symptoms of snoring, interrupted sleep, daytime somnolence-particularly if associated with tonsillar hypertrophy-appear in children during GH therapy.


Assuntos
Hormônio do Crescimento Humano/efeitos adversos , Síndromes da Apneia do Sono/induzido quimicamente , Adenoidectomia , Tonsila Faríngea/patologia , Humanos , Hipertrofia/induzido quimicamente , Hipertrofia/cirurgia , Tonsila Palatina/patologia , Polissonografia , Síndromes da Apneia do Sono/diagnóstico , Tonsilectomia
14.
Acta Paediatr Suppl ; 88(433): 112-4, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10626559

RESUMO

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m2/day (1 mg/m2/day) (n = 35) or no intervention (n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in response to clonidine stimulation were universally low, and mean (+/- SD) insulin-like growth factor I SDS was -1.2 +/- 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 +/- 2.5 to 4.6 +/- 2.9 (p < 0.0001), mean percentage body fat decreased from 46.3 +/- 8.4% to 38.4 +/- 10.7% (p < 0.001), mean lean body mass increased from 20.5 +/- 6.3 kg to 25.6 +/- 4.3 kg (p < 0.01) and respiratory muscle function and physical strength improved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 (p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Adolescente , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Criança , Pré-Escolar , Metabolismo Energético/efeitos dos fármacos , Humanos
18.
Osteoporos Int ; 18(3): 351-62, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17120182

RESUMO

INTRODUCTION: The study was designed to compare the bone anabolic effects of basic fibroblast growth factor (bFGF), a selective agonist for prostaglandin E receptor subtype EP4, and parathyroid hormone (PTH) in aged ovariectomized (OVX) rats with severe cancellous osteopenia. METHODS: Groups of aged OVX rats were maintained untreated for 1 year postovariectomy (15 months of age) to develop severe tibial cancellous osteopenia. These animals were then treated with bFGF or the EP4 agonist (EP4) for 3 weeks. Other groups of aged OVX rats were treated with EP4 or PTH alone for 11 weeks, or sequentially with bFGF or EP4 for 3 weeks followed by PTH for 8 weeks. Cancellous and cortical bone histomorphometry were performed in the right proximal tibial metaphysis and tibial diaphysis respectively. RESULTS: Treatment with bFGF for 3 weeks markedly increased serum osteocalcin, osteoid volume, and osteoblast and osteoid surfaces to a greater extent than EP4. Basic FGF, but not EP4 or PTH, induced formation of osteoid islands within bone marrow. EP4 stimulated cancellous bone turnover, but failed to restore lost cancellous bone in the severely osteopenic proximal tibia after 11 weeks of treatment. In contrast, EP4, much like PTH, increased cortical bone mass in the tibial diaphysis by stimulating both periosteal and endocortical bone formation. Treatment of aged OVX rats with PTH alone tended to partially reverse the severe tibial cancellous osteopenia, whereas sequential treatment with bFGF and PTH increased tibial cancellous bone mass to near the level of vehicle-treated control rats. These findings indicate that bFGF had the strongest stimulatory effect on cancellous bone formation, and was the only anabolic agent to induce formation of osteoid islands within the bone marrow of the severely osteopenic proximal tibia. Therefore, bFGF may be more effective for the reversal of severe cancellous osteopenia. PTH and EP4 increased cortical bone mass to nearly the same extent, but cancellous bone mass was greater by two-fold in PTH-treated OVX rats than in EP4-treated OVX rats. CONCLUSION: These findings in aged OVX rats suggest that PTH is more efficacious than EP4 for augmentation of cancellous bone in the severely osteopenic, estrogen-deplete skeleton.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Hormônio Paratireóideo/uso terapêutico , Receptores de Prostaglandina E/agonistas , Animais , Peso Corporal/efeitos dos fármacos , Doenças Ósseas Metabólicas/patologia , Doenças Ósseas Metabólicas/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Osteocalcina/sangue , Ovariectomia , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP4 , Tíbia/patologia
19.
J Hematother ; 1(1): 27-33, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1365014

RESUMO

Peripheral blood stem cells (PBSC) can be used for hematopoietic reconstitution in patients who have received high-dose chemotherapy (HDC). Previously, we reported 18 such patients who had nonmobilized PBSC harvested in steady state. We have now performed PBSC reinfusion in 24 patients with hypocellular or tumor-involved marrow who received cyclophosphamide (Cy) mobilization (4 grams/m2) prior to PBSC collection. The PBSC were collected upon rebound hematopoietic recovery by continuous-flow leukapheresis and subsequently cryoproserved. A median of 3.17 x 10(8) mononuclear cells/kg (range 1.47-3.95 x 10(8)) were collected. Patients underwent a median of 6 apheresis procedures (range 5-12). To date all 24 patients have undergone PBSC reinfusion after HDC. Fourteen patients received post-reinfusion granulocyte/macrophage colony-stimulating factor. Granulocyte recovery (> 500 x 10(6)/ml) has occurred at a median of 13.5 days (range 7-39) and platelet recovery (> 50 x 10(9)/ml without transfusion support) has occurred in 20 patients at a median of 33 days (range 7-121 days). Four other patients have platelet counts of greater than 20K and are transfusion independent, but have still not achieved counts of 50K. PBSC collection after Cy mobilization is feasible and effective for hematopoietic reconstitution after HDC and reinfusion. All 24 patients demonstrated trilineage engraftment. Although neutrophil recovery was not significantly hastened (as compared with our nonmobilized or steady-state data), time to platelet engraftment was foreshortened.


Assuntos
Antineoplásicos/uso terapêutico , Medula Óssea/patologia , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Contagem de Células , Feminino , Humanos , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
20.
Ophthalmology ; 102(12): 2012-5, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9098309

RESUMO

BACKGROUND: Hemangiomas pose a therapeutic challenge because they can threaten vision in infancy and early childhood. Intralesional injection of corticosteroid is widely regarded as the treatment of choice for hemangiomas which induce strabismus or significant refractive error, or occlude the visual axis. Ocular and systemic complications such as eyelid necrosis, central retinal artery occlusion, and adrenal suppression have been reported rarely after corticosteroid injection. METHODS: Three infants were treated with clobetasol propionate (Temovate) cream for vision-threatening eyelid hemangiomas. RESULTS: Treatment with this topical fluorinated corticosteroid produced a measurable reduction in the size of the hemangiomas, which permitted clearing of the visual axis. No regional side effects were noted. In addition, the patients did not demonstrate evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: This treatment modality appears to provide an additional alternative for managing superficial periocular hemangiomas which threaten vision.


Assuntos
Anti-Inflamatórios/uso terapêutico , Clobetasol/análogos & derivados , Neoplasias Palpebrais/tratamento farmacológico , Hemangioma Capilar/tratamento farmacológico , Administração Tópica , Anti-Inflamatórios/efeitos adversos , Pré-Escolar , Clobetasol/efeitos adversos , Clobetasol/uso terapêutico , Neoplasias Palpebrais/patologia , Feminino , Glucocorticoides , Hemangioma Capilar/patologia , Humanos , Lactente , Masculino , Pomadas , Resultado do Tratamento
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