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1.
J Anim Sci ; 89(11): 3690-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21724938

RESUMO

To investigate the influence of maternal Se supply and plane of nutrition on lamb morbidity, mortality, and passive transfer of IgG, pregnant ewe lambs were used in 2 experiments with 2 × 3 factorial treatment arrangements. Supplementation of Se began at breeding and was either adequate Se (ASe, 9.5 µg/kg of BW) or high Se (HSe, 81.8 µg/kg of BW) in Exp. 1 or ASe (11.5 µg/kg of BW) or HSe (77.0 µg/kg of BW) in Exp. 2. On d 50 or 40 of gestation for Exp. 1 or 2, respectively, ewes were assigned randomly to 1 of 3 nutritional planes: 60% (RES), 100% (control, CON), or 140% (HI) of NRC requirements. This resulted in the following treatments: ASe-RES, ASe-CON, ASe-HI, HSe-RES, HSe-CON, and HSe-HI. Upon parturition, lambs were separated from their dams and serum samples obtained. Lambs were fed artificial colostrum for the first 20 h and then placed on milk replacer and grain pellets until completion of the study (Exp. 1, 57 d; Exp. 2, 21 d). Twenty-four hours after parturition, lamb serum samples were collected for IgG analysis. All lambs were reared similarly and morbidity and mortality assessed. Main effects were considered significant when P ≤ 0.05. In Exp. 1, there was a Se × plane of nutrition interaction (P ≤ 0.01) for lamb morbidity from birth to weaning and for 24-h IgG concentration. Lambs from ASe-RES and HSe-HI ewes were treated more frequently (P < 0.01) for respiratory and gastrointestinal disease, and lambs from HSe-HI ewes had the smallest (P < 0.01) 24-h serum IgG concentration. In Exp. 1, lambs from HI ewes also had the greatest (P < 0.01) mortality rates from birth to weaning compared with lambs from CON and RES ewes. In Exp. 2, there was an effect (P < 0.01) of maternal plane of nutrition with lambs from RES ewes having increased 24-h IgG compared with lambs from CON and HI ewes. There was no effect of maternal Se supplementation on lamb 24-h IgG in Exp. 2; however, there was a Se × plane of nutrition interaction (P < 0.01) for morbidity. From birth to 21 d of age, lambs from ASe-CON ewes had fewer (P < 0.01) treatment days compared with lambs from any of the other treatment groups. There also tended (P = 0.08) to be an effect of maternal Se supplementation on lamb mortality with increased mortality observed in lambs from HSe ewes. Results from the studies show a restricted maternal plane of nutrition can increase lamb serum IgG concentration. Selenium results were not consistent between the 2 experiments and may be due to differences in maternal Se.


Assuntos
Suplementos Nutricionais/normas , Fenômenos Fisiológicos da Nutrição Materna/imunologia , Estado Nutricional/imunologia , Selênio/farmacologia , Ovinos/imunologia , Animais , Animais Recém-Nascidos , Peso ao Nascer/imunologia , Feminino , Imunoglobulina G/sangue , Tamanho da Ninhada de Vivíparos/imunologia , Masculino , Gravidez , Distribuição Aleatória , Selênio/administração & dosagem
2.
J Anim Sci ; 89(11): 3819-23, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21622885

RESUMO

The effects of maternal nutrition on offspring wool production (quality and quantity) were evaluated. Primiparous Rambouillet ewes (n = 84) were randomly allocated to 1 of 6 treatments in a 2 × 3 factorial design. Selenium treatment [adequate Se (ASe, 9.5 µg/kg of BW) vs. high Se (HSe, 81.8 µg/kg of BW)] was initiated at breeding, and maternal nutritional intake [control (CON, 100% of requirements) vs. restricted (60% of CON) vs. overfed (140% of CON)] was initiated at d 50 of gestation. Lamb birth weight was recorded at delivery, and all lambs were placed on the same diet immediately after birth to determine the effects of prenatal nutrition on postnatal wool production and follicle development. At 180 ± 2.2 d of age, lambs were necropsied and pelt weights were recorded. Wool samples were collected from the side and britch areas, whereas skin samples were collected from the side of each lamb only. Although Se status did not influence side staple length in males, female lambs born from ewes on the ASe treatment had a shorter staple length (P < 0.05) when compared with females from ewes on the HSe treatment. Maternal nutritional intake and Se status did not influence (P ≥ 0.23) wool characteristics on the britch. However, at the britch, wool from female lambs had a reduced comfort factor (P = 0.01) and a greater (P = 0.02) fiber diameter compared with wool from male lambs. Maternal Se supplementation, maternal nutritional plane, sex of the offspring, or their interactions had no effect (P > 0.13) on primary (29.10 ± 1.40/100 µm(2)) and secondary (529.84 ± 21.57/100 µm(2)) wool follicle numbers. Lambs from ASe ewes had a greater (P = 0.03) secondary:primary wool follicle ratio compared with lambs from HSe ewes (20.93 vs. 18.01 ± 1.00). Despite similar postnatal diets, wool quality was affected by maternal Se status and the maternal nutritional plane.


Assuntos
Suplementos Nutricionais , Estado Nutricional/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Selênio/farmacologia , Ovinos/fisiologia , Lã/ultraestrutura , Animais , Animais Recém-Nascidos , Peso ao Nascer/fisiologia , Feminino , Histocitoquímica/veterinária , Análise dos Mínimos Quadrados , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Distribuição Aleatória
3.
J Anim Sci ; 89(5): 1627-39, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21521822

RESUMO

The objectives were to investigate effects of nutritional plane and Se supply during gestation on yield and nutrient composition of colostrum and milk in first parity ewes. Rambouillet ewe lambs (n = 84, age = 240 ± 17 d, BW = 52.1 ± 6.2 kg) were allocated to 6 treatments in a 2 × 3 factorial array. Factors included Se [adequate Se (ASe, 11.5 µg/kg of BW) or high Se (HSe, 77.0 µg/kg of BW)] initiated at breeding, and nutritional plane [60 (RES), 100 (CON), or 140% (HIH) of requirements] initiated at d 40 of gestation. Ewes were fed individually from d 40, and lambs were removed at parturition. Colostrum was milked from all ewes at 3 h postpartum, and one-half of the ewes (n = 42) were transitioned to a common diet meeting lactation requirements and mechanically milked for 20 d. Colostrum yield was greater (P = 0.02) for HSe ewes than ASe, whereas CON had greater (P < 0.05) colostrum yield than RES and HIH. Colostrum Se (%) was greater (P < 0.01) for HSe than ASe. Colostrum from ewes fed HSe had less (P = 0.03) butterfat (%), but greater (P ≤ 0.05) total butterfat, solids-not-fat, lactose, protein, milk urea N, and Se than ASe. Colostrum from HIH ewes had greater (P ≤ 0.02) solids-not-fat (%) than RES, whereas RES had greater (P ≤ 0.04) butterfat (%) than CON and HIH. Colostrum from ewes fed the CON diet had greater (P = 0.01) total butterfat than HIH. Total solids-not-fat, lactose, and protein were greater (P < 0.05) in colostrum from CON than RES and HIH. Ewes fed HSe had greater (P < 0.01) milk yield (g/d and mL/d) than ASe, and CON and HIH had greater (P < 0.01) yield than RES. Milk protein (%) was greater (P ≤ 0.01) in RES compared with CON or HIH. Ewes fed HSe had greater (P < 0.01) milk Se (µg/g and mg/d) than ASe on each sampling day. Milk from CON and HIH ewes had greater (P < 0.01) total solids-not-fat, lactose, protein, and milk urea N than RES. Total Se was greater (P = 0.02) in milk from ewes fed the CON diet compared with RES. Somatic cell count and total somatic cells were greater (P ≤ 0.05) in milk from CON than RES. A cubic effect of day (P ≥ 0.01) was observed for milk yield (g and mL). Butterfat, solids-not-fat, lactose, milk urea N, and Se concentration responded quadratically (P ≤ 0.01) to day. Protein (%), total butterfat, and total Se, and somatic cells (cells/mL and cells/d) decreased linearly (P < 0.01) with day. Results indicate that gestational nutrition affects colostrum and milk yield and nutrient content, even when lactational nutrient requirements are met.


Assuntos
Colostro/química , Dieta/veterinária , Leite/química , Selênio/administração & dosagem , Ovinos/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ingestão de Alimentos/fisiologia , Feminino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Distribuição Aleatória , Selênio/metabolismo
4.
Domest Anim Endocrinol ; 39(4): 240-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20920781

RESUMO

To examine effects of maternal nutrition and Se intake on adiposity and insulin sensitivity in female offspring, treatments were imposed during gestation on 82 pregnant primiparous Rambouillet ewe lambs (52.2 ± 0.8 kg) allotted randomly to 1 of 6 treatments in a 2 × 3 factorial arrangement. Factors were adequate (9.5 µg Se·kg BW(-1)·d(-1); ASe) or high (81.8 µg Se·kg BW(-1)·d(-1); HSe) levels of dietary Se (Se-enriched yeast) and maternal nutritional intake (100% of metabolizable energy [ME] requirement [MOD], 60% of MOD [LOW], and 140% of MOD [HIGH]). Selenium treatments were initiated at breeding and global nutritional treatments at day 50 of gestation. At parturition, lambs were removed from ewes before nursing and managed similarly. Glucose tolerance tests were performed at 107 and 148 d of age. Necropsies were performed at 180 d of age. Although there was no effect of Se on maternal body condition or weight during gestation, both maternal nutritional intake and selenium treatment influenced (P ≤ 0.04) offspring growth and response to a glucose tolerance test. Female lambs from HSe ewes were heavier (P = 0.04) at birth. There were nutritional intake and Se interactions (P ≤ 0.05) on the growth rate of the lambs and their insulin response to a glucose bolus at 2 different times during growth. By 180 d, ewe lambs from HSe ewes had more (P ≤ 0.07) internal fat stores than lambs from ASe ewes. It appears that both maternal nutritional level and Se intake can influence insulin sensitivity, and maternal Se intake alone can enhance fat deposition in female offspring.


Assuntos
Adiposidade , Dieta , Teste de Tolerância a Glucose/veterinária , Efeitos Tardios da Exposição Pré-Natal/veterinária , Selênio/administração & dosagem , Ovinos/fisiologia , Animais , Composição Corporal , Ingestão de Energia , Feminino , Insulina/sangue , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ovinos/crescimento & desenvolvimento , Ovinos/metabolismo
5.
J Anim Sci ; 88(11): 3645-56, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20656981

RESUMO

Lambs born from feed-restricted or overfed ewes can be lighter at birth, whereas maternal Se supplementation can increase fetal size near term. We hypothesized that birth weight would be inversely related to feed efficiency and growth rates during postnatal development. To examine the effects of maternal dietary Se and nutrient restriction or excess on postnatal lamb growth, diet digestibility, and N retention, 82 ewe lambs (52.2 ± 0.8 kg) were allotted randomly to 1 of 6 treatments in a 2 × 3 factorial arrangement. Factors were dietary Se [adequate Se (9.5 µg/kg of BW; ASe) vs. high Se (Se-enriched yeast; 81.8 µg/kg of BW; HSe)] and maternal nutritional intake [60% (restricted, RES), 100% (control, CON), or 140% (high, HI) of NRC requirements]. Selenium treatments began at breeding. Nutritional treatments began on d 50 of gestation. Lambs were immediately removed from their dams at parturition, provided artificial colostrum, and fed milk replacer until weaning. After weaning, lambs were maintained using common management and on common diets until necropsy at 180 d. Male and female lambs from RES-fed ewes were lighter (P ≤ 0.03) at birth than lambs from CON-fed ewes, with lambs from HI-fed ewes being intermediate. Although maternal nutritional intake influenced (P < 0.06) BW gain before weaning on d 57, both maternal nutritional intake and sex of offspring influenced (P ≤ 0.09) BW gain from d 57 to 180. Although maternal nutritional intake did not influence (P ≥ 0.35) female lamb BW gain, male lambs from RES-fed ewes were lighter (P ≤ 0.09) than those from CON-fed ewes until d 162. By d 180, male lambs from RES- and HI-fed ewes were lighter (P ≤ 0.09) than those from CON-fed ewes. In a subset of lambs used in a feed efficiency study, namely, those born to ASe ewes, HI maternal nutritional intake decreased (P ≤ 0.09) ADG and G:F compared with lambs born to RES- and CON-fed ewes, which did not differ (P ≥ 0.60). Conversely, when lambs were born to HSe ewes, HI maternal nutritional intake increased (P ≤ 0.01) ADG and G:F compared with CON, with RES being intermediate. Moreover, lambs born to ASe-HI ewes had decreased (P < 0.01) ADG and G:F compared with lambs born to HSe-HI ewes. Furthermore, male lambs had a greater (P < 0.01) G:F than female lambs. Maternal diet did not affect (P ≥ 0.11) N retention in male lambs. These data indicate that maternal nutrition during gestation and sex of the offspring alter postnatal growth and efficiency of growth in offspring despite similar postnatal management.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Dieta/veterinária , Digestão/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Selênio/farmacologia , Ovinos/crescimento & desenvolvimento , Envelhecimento , Animais , Suplementos Nutricionais , Ingestão de Alimentos , Feminino , Masculino , Nitrogênio/metabolismo , Gravidez , Selênio/sangue , Caracteres Sexuais , Aumento de Peso
6.
J Anim Sci ; 88(13 Suppl): E61-72, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20023136

RESUMO

Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.


Assuntos
Criação de Animais Domésticos/métodos , Animais Domésticos/crescimento & desenvolvimento , Desenvolvimento Fetal/fisiologia , Circulação Placentária/fisiologia , Animais , Animais Domésticos/embriologia , Animais Domésticos/fisiologia , Bovinos/embriologia , Bovinos/crescimento & desenvolvimento , Bovinos/fisiologia , Feminino , Masculino , Modelos Biológicos , Placenta/embriologia , Placenta/fisiologia , Gravidez , Ovinos/embriologia , Ovinos/crescimento & desenvolvimento , Ovinos/fisiologia
7.
Theriogenology ; 70(2): 227-32, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18501957

RESUMO

The effects of melengestrol acetate (MGA) and P.G. 600 on ewe fertility outside the natural breeding season were evaluated. Rambouillet ewes were assigned to one of four groups: (1) control (C; n=92); (2) PG600 (n=86); (3) MGA (n=99); and (4) MGA+PG600 (n=92). A pellet with or without MGA (0.3mg/ewe/d) was fed at 0.15kg/ewe/d for 7d. On the last day of pellet feeding, ewes were given either saline or 5mL of P.G. 600 i.m. (400IU equine chorionic gonadotropin (eCG) and 200IU human chorionic gonadotropin (hCG)). Ultrasonography was performed between Days 20 and 25 of gestation for ewes that were mated during the first 6 d of the breeding period from the MGA (n=15) and MGA+PG600 (n=8) groups, and the number of luteal structures and embryos were counted. During the first 6d of the breeding period, MGA increased (P<0.05) the percentage of ewes that mated and conceived when compared to C and PG600 (24.2% vs. 3.3% and 10.5%, respectively). Relative to MGA, the mean (+/-S.E.M.) number of luteal structures per ewe was enhanced (P<0.03) in MGA+PG600 (1.53+/-0.13 vs. 2.38+/-0.42, respectively), however as pregnancy progressed, the number of embryos (1.5+/-0.13 vs. 1.8+/-0.16, respectively) and lambs born (1.3+/-0.15 vs. 1.5+/-0.27, respectively) did not differ. Treatment with MGA reduced (P<0.01) the interval from ram introduction to lambing relative to groups that did not receive MGA (168+/-0.8d vs. 171+/-0.6d, respectively). In conclusion, treatment with MGA increased the percentage of ewes conceiving early in the breeding period. Although P.G. 600 increased the number of luteal structures present per ewe, it did not significantly enhance ewe prolificacy.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Fertilidade/efeitos dos fármacos , Gonadotropinas Equinas/administração & dosagem , Gonadotropinas Equinas/farmacologia , Acetato de Melengestrol/administração & dosagem , Acetato de Melengestrol/farmacologia , Aborto Animal , Animais , Peso ao Nascer , Cruzamento , Combinação de Medicamentos , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Masculino , Gravidez , Taxa de Gravidez , Estações do Ano , Ovinos
8.
J Anim Sci ; 86(9): 2415-23, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18441080

RESUMO

To examine effects of nutritional plane and Se supplementation on colostrum quality and mammary development, individually fed, pregnant Rambouillet ewe lambs were allotted randomly to 1 of 6 treatments in a 2 x 3 factorial arrangement. Main effects included dietary Se level, which began at breeding (d = 0) [adequate Se (9.5 mug/kg of BW) vs. high Se (81.8 mug/kg of BW)], and plane of nutrition, which began at d 50 of gestation [60% (RES), 100% (CON), and 140% (HIGH) of requirements]. Upon parturition, lambs were immediately separated from dams and weighed. Three hours after lambing, colostrum yield was determined, and samples were obtained for components and immunoglobulin G (IgG) analysis. Ewes were slaughtered within 24 h of parturition, and mammary tissues were collected for determination of alveolar secretory epithelial cell proliferation index and luminal area. Gestation length was reduced (P < 0.01) in HIGH ewes compared with RES and CON ewes. Although birth weights were reduced (P < 0.01) in RES and HIGH compared with CON ewes, there was little effect of diet on placental size. Mammary gland weight was reduced (P /= 0.15) on mammary gland weight, colostrum quantity, or IgG concentration in pregnant ewe lambs. Improper nutrition from mid to late pregnancy in ewe lambs altered colostrum quality and quantity and reduced offspring birth weight, which may have negative implications for lamb health and survival during the early postnatal period.


Assuntos
Colostro/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Estado Nutricional/fisiologia , Selênio/administração & dosagem , Ovinos/fisiologia , Animais , Animais Recém-Nascidos , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Processos de Crescimento Celular/efeitos dos fármacos , Colostro/fisiologia , DNA/metabolismo , Feminino , Histocitoquímica/veterinária , Imunoglobulina G/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/fisiologia , Placenta/fisiologia , Gravidez , RNA/metabolismo , Distribuição Aleatória
9.
Placenta ; 27 Suppl A: S61-8, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16442614

RESUMO

The risks of miscarriage, prematurity and low birth weight are particularly acute in adolescent girls who are still growing at the time of conception. The role of maternal nutrition in mediating pregnancy outcome in this vulnerable group has been examined in sheep models. When singleton bearing adolescent dams are overnourished to promote rapid maternal growth throughout pregnancy, growth of both the placenta and fetus is impaired, and birth occurs prematurely relative to control adolescents of equivalent age. Studies at mid-gestation, prior to alterations in placental mass, suggest that reduced proliferation of the fetal trophectoderm, impaired angiogenesis, and attenuated uteroplacental blood flows are early defects in placental development. By late pregnancy, relative placental mass is reduced by 45% but uteroplacental metabolism and placental glucose transfer capacity remain normal when expressed on a placental weight specific basis. The asymmetrically growth-restricted fetuses are hypoxic, hypoglycemic and have reduced insulin and IGF-1 concentrations. Absolute umbilical nutrient uptakes are attenuated but fetal utilisation of glucose, oxygen and amino acids remains normal on a fetal weight basis. This suggests altered sensitivities to metabolic signals and may have implications for subsequent metabolic health. At the other end of the nutritional spectrum, many girls who become pregnant have inadequate or marginal nutritional status during pregnancy. This situation is replicated in a second model whereby dams are prevented from growing during pregnancy by relatively underfeeding. Limiting maternal intake in this way gradually depletes maternal body reserves leading to a lower transplacental glucose gradient and a modest slowing of fetal growth in late pregnancy. These changes appear to be independent of alterations in placental growth per se. Thus, while the underlying mechanisms differ, maternal intake at both ends of the nutritional spectrum is a powerful determinant of fetal growth in pregnant adolescents.


Assuntos
Desenvolvimento Fetal , Fenômenos Fisiológicos da Nutrição Materna , Resultado da Gravidez , Gravidez na Adolescência/fisiologia , Adolescente , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Retardo do Crescimento Fetal , Humanos , Desnutrição , Modelos Animais , Placenta/irrigação sanguínea , Placenta/fisiologia , Gravidez , Ovinos , Comportamento Social , Útero/irrigação sanguínea
10.
Neurology ; 54(3): 630-4, 2000 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-10680795

RESUMO

OBJECTIVE: To determine seizure outcome and its predictors in patients with medically refractory temporal lobe epilepsy (TLE) after temporal lobectomy (TL). BACKGROUND: TL is the most common surgical procedure performed in adolescents and adults for the treatment of medically refractory TLE. Seizure outcome has been reported extensively during the first few postoperative years, but little is known beyond that time. METHODS: The authors analyzed seizure outcome in 79 patients who underwent TL for epilepsy at the Duke University Medical Center from 1962 through 1984. Patients with less than 2 years of follow-up and degenerative disorders were excluded. Predictors of seizure outcome were analyzed using Kaplan-Meier survival analyses. RESULTS: The mean follow-up was 14 years (range, 2.1 to 33.6 years). Using Engel's classification, 65% of patients were class I, 15% were class II, 11% were class III, and 9% were class IV. At least one postoperative seizure occurred in 55% of subjects. The majority of recurrences (86%) took place within 2 years of surgery. Later recurrences tended not to lead to medical intractability. Higher monthly preoperative seizure frequency was associated with poor seizure outcome. A seizure-free state at 2 years was found to be a better predictor of long-term outcome than the 6-, 12-, and 18-month landmarks. CONCLUSIONS: TL provides sustained, long-term benefit in patients with medically refractory TLE. Seizure-free status at 2 years from the time of surgery is predictive of long-term remission.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Lobo Temporal/cirurgia , Adulto , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Masculino , Prognóstico , Análise de Sobrevida , Fatores de Tempo
11.
Neurology ; 51(6): 1723-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9855532

RESUMO

The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80% arose from the hippocampi and 20% from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.


Assuntos
Encefalopatias/diagnóstico , Ventrículos Cerebrais , Coristoma/diagnóstico , Epilepsia Parcial Complexa/diagnóstico , Adulto , Encefalopatias/complicações , Coristoma/complicações , Eletrodos , Eletroencefalografia , Epilepsia Parcial Complexa/etiologia , Feminino , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino
13.
Anticancer Drugs ; 2(4): 357-63, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1797191

RESUMO

The arylmethylaminopropanediols (AMAPs) are a new class of DNA intercalators. 773U82.HCl is the second of these compounds to enter clinical trial. Significant antitumor activity for 773U82.HCl was documented in a variety of murine and human tumor models. This phase I study examined a 1-, 2- and 6-hour infusion given every 28 days. Thirty-six patients received 58 courses of drug at doses ranging from 15 mg/m2 to 980 mg/m2. The dose-limiting toxicity of 773U82.HCl was hemolysis noted at 980 mg/m2. Change in color of the plasma and decreases in haptoglobin were correlated with drug concentrations of the infusate greater than or equal to 3 mg/ml. Clinically significant changes in hemoglobin levels requiring blood transfusions did not occur. Neurologic toxicity occurred at 720 mg/m2 with the most severe neurologic toxicity occurring in a patient with the highest peak plasma concentration (4.1 micrograms/ml). With an increase in duration of the infusion and amount of fluid administered, the neurologic toxicity resolved. Other toxicities included mild nausea and vomiting and a dose-related phlebitis. Pharmacokinetic studies were completed in 22 patients. The mean terminal t1/2 beta was 4.4 h with a mean apparent volume of distribution at steady state (Vdss) of 314 l/m2. The mean total body clearance was 72 l/h/m2. Peak plasma levels ranged from 0.04 to 4.14 micrograms/ml. Further studies with 773U82.HCl on this schedule at the doses studied are not recommended. Hematologic monitoring for evidence of intravascular hemolysis should be included in future studies with 773U82.HCl.


Assuntos
Fluorenos/uso terapêutico , Substâncias Intercalantes/uso terapêutico , Neoplasias/tratamento farmacológico , Propilenoglicóis/uso terapêutico , Adulto , Idoso , Avaliação de Medicamentos , Feminino , Fluorenos/farmacocinética , Fluorenos/toxicidade , Hemólise/efeitos dos fármacos , Humanos , Substâncias Intercalantes/farmacocinética , Substâncias Intercalantes/toxicidade , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Flebite/induzido quimicamente , Propilenoglicóis/farmacocinética , Propilenoglicóis/toxicidade , Vômito/induzido quimicamente
14.
Sel Cancer Ther ; 7(2): 85-91, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1754731

RESUMO

Crisnatol is an arylmethylaminopropanediol derivative that has shown promise as an antitumor agent in preclinical testing. In a phase I trial using a monthly six-hour infusion schedule the recommended dose for future phase II trials was found to be 388 mg/m2. Neurologic toxicity was dose-limiting in that trial and correlated with the attainment of a threshold plasma concentration of greater than 4.5 micrograms/ml. In this study we treated 15 patients with escalating doses of crisnatol from 450 mg/m2 to 900 mg/m2 administered at a rate of 50 mg/m2/hr over 9, 12, 15, and 18 hours. Toxicity was mild to moderate at all dose levels. However, serious central nervous system effects were noted in one patient at 900 mg/m2 over 18 hours whose plasma level was 6.5 micrograms/ml. This study has demonstrated higher total doses of crisnatol can be given if the drug is administered as a prolonged infusion in an attempt to avoid high plasma levels of the agent.


Assuntos
Antineoplásicos/uso terapêutico , Crisenos/uso terapêutico , Neoplasias/tratamento farmacológico , Propilenoglicóis/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Crisenos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Avaliação de Medicamentos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Propilenoglicóis/efeitos adversos
15.
Neurology ; 40(3 Pt 1): 413-8, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2314581

RESUMO

We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes.


Assuntos
Epilepsia do Lobo Temporal/cirurgia , Lobo Temporal/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Prognóstico , Estudos Prospectivos
16.
Cancer Res ; 48(16): 4706-10, 1988 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-3396016

RESUMO

Crisnatol is a novel lipophilic arylmethylaminopropanediol with significant antineoplastic activity in a variety of murine and human tumor models which functions as a DNA intercalator. In this Phase I trial, a 6-h infusion of the drug was administered i.v. in 700 to 1500 ml of 5% dextrose in water every 28 days. Eighty-five courses at doses of 7.5 to 516 mg/m2 were administered to 43 patients with refractory solid tumors. Reversible neurological toxicity was dose limiting at 516 mg/m2 and was manifested as somnolence, dizziness, blurred vision, unsteady gait, and alpha-slowing on electroencephalogram at the end of infusion. All neurological signs and symptoms were reversible. No hematological toxicity was observed. Other toxicities included phlebitis, mild to moderate nausea and vomiting, reversible sinus node arrest in one patient, and hypertension. Crisnatol plasma concentrations were determined by high-pressure liquid chromatography. After infusion, plasma concentrations declined biexponentially with a terminal t1/2 of 2.9 h. Using a two-compartment model, the mean apparent volume of distribution at steady state and total-body clearance were 58.8 liters/m2 and 18.3 liters/h/m2, respectively, indicative of extensive tissue distribution and rapid hepatic clearance. Peak plasma levels occurred at the end of infusion and correlated with the onset of neurological toxicity. The recommended Phase II dose for this schedule is 388 mg/m2.


Assuntos
Antineoplásicos/efeitos adversos , Crisenos/efeitos adversos , Neoplasias/tratamento farmacológico , Fenantrenos/efeitos adversos , Propilenoglicóis , Adulto , Idoso , Antineoplásicos/administração & dosagem , Arritmias Cardíacas/induzido quimicamente , Pressão Sanguínea/efeitos dos fármacos , Sistema Digestório/efeitos dos fármacos , Esquema de Medicação , Avaliação de Medicamentos , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/efeitos dos fármacos
18.
Int J Psychiatry Med ; 14(1): 57-63, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6145675

RESUMO

The clinical manifestations, differential diagnosis, and treatment of the neuroleptic malignant syndrome and neuroleptic-induced catatonia are discussed. A case is presented in which the catatonic-like behavior and extrapyramidal sequelae of the neuroleptic malignant syndrome responded to combined treatment with anticholinergics and levodopa/carbidopa. Differential diagnosis and theories regarding the development of these neuroleptic-induced disorders are reviewed.


Assuntos
Antipsicóticos/efeitos adversos , Doenças dos Gânglios da Base/induzido quimicamente , Catatonia/induzido quimicamente , Haloperidol/efeitos adversos , Idoso , Doenças dos Gânglios da Base/tratamento farmacológico , Carbidopa/administração & dosagem , Catatonia/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Haloperidol/antagonistas & inibidores , Humanos , Levodopa/administração & dosagem , Síndrome , Triexifenidil/administração & dosagem
19.
J Neurosurg ; 58(4): 531-7, 1983 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6338167

RESUMO

A double-blind study was performed to compare metrizamide with the new iodinated water-soluble nonionic contrast medium, iopamidol, for conventional and computerized tomography lumbosacral myelography. Both contrast agents were used in 30 patients, and were equivalent in terms of image quality and clinical accuracy. Headaches and nausea were less severe using iopamidol. The most striking difference was found in adverse neurobehavioral reactions and associated electroencephalographic abnormalities, which were noted in 17% of the metrizamide group but were not seen with the use of iopamidol. Iopamidol appears to be superior to metrizamide for intrathecal applications. An explanation of the differential neurotoxicity is provided.


Assuntos
Ácido Iotalâmico/análogos & derivados , Metrizamida , Mielografia/normas , Ensaios Clínicos como Assunto , Método Duplo-Cego , Humanos , Iopamidol , Ácido Iotalâmico/efeitos adversos , Região Lombossacral , Metrizamida/efeitos adversos , Tomografia Computadorizada por Raios X
20.
Ann Neurol ; 12(5): 458-62, 1982 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6817695

RESUMO

The purposes of this study were to obtain a detailed description of the clinical features of pseudoepileptic (PE) seizures, to try to reproduce these events in the laboratory during a single recording, and to establish a framework useful to the clinician for evaluating patients whose behavior suggests physiological seizures, but about which doubt remains. We analyzed 37 episodes of PE seizures recorded in 30 patients during a single three-hour video/EEG recording. The PE seizures occurred spontaneously or were induced by sequential activation procedures. The historical information together with behavioral observations show that the PE seizures mimicked primary generalized seizures in 15 episodes, elementary partial seizures with secondary generalization in 21 episodes, and complex partial seizures in a single episode. Our data underscore the usefulness of the video/EEG recording method and suggest activation techniques which, combined with detailed historical information, aid in establishing the diagnosis of PE seizures.


Assuntos
Epilepsia/diagnóstico , Gravação de Videoteipe , Adolescente , Adulto , Criança , Diagnóstico Diferencial , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico , Potenciais Evocados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/diagnóstico
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