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1.
BMC Cancer ; 16(1): 710, 2016 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-27589870

RESUMO

BACKGROUND: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone. However, NAC carries the risk of toxicity and is associated with a decrease in physical fitness, which may in turn influence subsequent clinical outcome. Lower levels of physical fitness are associated with worse outcome following major surgery in general and Upper Gastrointestinal Surgery (UGI) surgery in particular. Cardiopulmonary exercise testing (CPET) provides an objective assessment of physical fitness. The aim of this study is to test the hypothesis that NAC prior to upper gastrointestinal cancer surgery is associated with a decrease in physical fitness and that the magnitude of the change in physical fitness will predict mortality 1 year following surgery. METHODS: This study is a multi-centre, prospective, blinded, observational cohort study of participants with oesophageal and gastric cancer scheduled for neoadjuvant cancer treatment (chemo- and chemoradiotherapy) and surgery. The primary endpoints are physical fitness (oxygen uptake at lactate threshold measured using CPET) and 1-year mortality following surgery; secondary endpoints include post-operative morbidity (Post-Operative Morbidity Survey (POMS)) 5 days after surgery and patient related quality of life (EQ-5D-5 L). DISCUSSION: The principal benefits of this study, if the underlying hypothesis is correct, will be to facilitate better selection of treatments (e.g. NAC, Surgery) in patients with oesophageal or gastric cancer. It may also be possible to develop new treatments to reduce the effects of neoadjuvant cancer treatment on physical fitness. These results will contribute to the design of a large, multi-centre trial to determine whether an in-hospital exercise-training programme that increases physical fitness leads to improved overall survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325883 - 29(th) March 2011.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias Gastrointestinais/terapia , Aptidão Física/fisiologia , Inglaterra , Teste de Esforço/métodos , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , País de Gales
2.
Dis Esophagus ; 26(3): 263-71, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23551569

RESUMO

The majority of esophagectomies in Western parts of the world are performed by a transthoracic approach reflecting the prevalence of adenocarcinoma of the lower esophagus or esophagogastric junction. Minimally invasive esophagectomy (MIE) has been reported in a variety of formats, but there are no series that directly compare totally minimally invasive thoracolaparoscopic 2 stage esophagectomy (MIE-2) with open Ivor Lewis (IVL). A prospective single-center cohort study of patients undergoing elective MIE-2 or IVL between January 2005 and November 2010 was performed. Short-term clinicopathologic outcomes were recorded using validated systems. One hundred and six patients (median age 66, range 36-85, 88 M : 18 F) underwent two-stage esophagectomy (53 MIE-2 and 53 IVL). Patient demographics (age, sex, body mass index, American Society of Anesthesiologists grade, tumor characteristics, neoadjuvant chemotherapy, and TNM stage) were comparable between the two groups. Outcomes for MIE-2 and IVL were comparable for anastomotic leak rates (5 [9%] vs. 2 [4%], P= 0.241), resection margin clearance (R0) (43 [81%] vs. 38 [72%], P= 0.253), median lymph node yield (19 vs. 18, P= 0.584), and median length of stay (12 [range 7-91] vs. 12 [range 7-101] days), respectively. Blood loss was significantly less for MIE-2 compared with IVL (median 300 [range 0-1250] mL vs. 400 [range 0-3000] mL, respectively, P= 0.021). MIE-2 in this series of selected patients supports its efficacy, when performed by an experienced minimally invasive surgical team. A well-designed multicenter trial addressing clinical effectiveness is now required.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/etiologia , Perda Sanguínea Cirúrgica , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Seguimentos , Humanos , Laparoscopia/métodos , Laparotomia/métodos , Tempo de Internação , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Prospectivos , Toracoscopia/métodos , Toracotomia/métodos , Resultado do Tratamento
3.
Nutr J ; 11: 84, 2012 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-23057785

RESUMO

BACKGROUND: There is abundant research relevant to genetic and environmental influences on asthma and hayfever, but little is known about dietary risk factors in Australian adults. This study's purpose was to identify dietary factors associated with lifetime asthma (AS) and asthma or hayfever (AS/HF) diagnosis in Australian middle-aged and older adults. METHODS: From The 45 and Up Study baseline self-report data, this study included 156,035 adult men and women. Participants were sampled from the general population of New South Wales, Australia in 2006-2009. About 12% of participants reported ever receiving an AS diagnosis (men 10%; women 14%) and 23% reported AS/HF diagnosis (men 19%; women 26%). Following principle components factor analysis, dietary items loaded onto one of four factors for men (meats/cheese; fruits/vegetables; poultry/seafood; grains/alcohol) or five factors for women (meats; fruits/vegetables; poultry/seafood; cereal/alcohol; brown bread/cheese). Logistic regression was used to analyze the associations between dietary factors and AS or AS/HF diagnosis. RESULTS: For men, the meats/cheese factor was positively associated with AS (AOR = adjusted odds ratio for highest versus lowest quintile = 1.18, 95%CI = 1.08, 1.28; P(trend) = 0.001) and AS/HF (AOR for highest versus lowest quintile = 1.22, 95%CI = 1.14, 1.29; P(trend) < 0.001). Poultry/seafood was also associated with AS/HF in men (AOR for highest versus lowest quintile = 1.11, 95%CI = 1.04, 1.17; P(trend) = 0.002). For women, significant risk factors for AS/HF included meats (AOR for highest versus lowest quintile = 1.25, 95%CI = 1.19, 1.31; P(trend) = 0.001), poultry/seafood (AOR for highest versus lowest quintile = 1.06, 95%CI = 1.01, 1.12; P(trend) = 0.016), and fruits/vegetables (AOR for highest versus lowest quintile = 1.07, 95%CI = 1.02, 1.12; P(trend) = 0.011). In contrast, the cheese/brown bread dietary factor was protective against AS in women (AOR for highest versus lowest quintile = 0.88, 95%CI = 0.82, 0.94; P(trend) < 0.001). CONCLUSIONS: Generally, diets marked by greater intakes of meats, poultry, and seafood were associated with diagnosed AS and AS/HF. Taken together, these findings suggest that adherence to a more meat-based diet may pose risk for AS and AS/HF in Australian adults.


Assuntos
Envelhecimento , Asma/etiologia , Dieta/efeitos adversos , Rinite Alérgica Sazonal/etiologia , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Asma/prevenção & controle , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Carne/efeitos adversos , Pessoa de Meia-Idade , New South Wales/epidemiologia , Prevalência , Análise de Componente Principal , Estudos Prospectivos , Rinite Alérgica Sazonal/epidemiologia , Rinite Alérgica Sazonal/prevenção & controle , Fatores de Risco , Alimentos Marinhos/efeitos adversos , Caracteres Sexuais
4.
Sci Total Environ ; 835: 155398, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35469882

RESUMO

The fate of plastics in rivers is a key component of the global plastic cycle. Plastics entering freshwater ecosystems are colonized by microbial biofilms, and microbe-plastic interactions can influence ecosystem processes and plastic fate. While literature examining the role of geographic region on plastic biofilms is quickly expanding, research which covers large (i.e., continental) spatial scales and includes freshwater ecosystems is warranted. In addition, most research focuses on bacterial communities, while biofilm eukaryotes are less commonly studied. We assessed biofilm metabolism and community structure on plastic (foamed polystyrene and polyvinyl chloride; PVC) and natural substrates (unglazed ceramic tile) in urban streams spanning a nested geographic gradient in the continental United States. We measured biofilm biomass, community respiration, and chlorophyll a, in addition to assessing marker gene-based community diversity of bacterial, fungal, and algal assemblages. Results demonstrated some substrate-specific trends in biofilm characteristics, including higher biofilm biomass on polystyrene across sites, and lower diversity of bacterial assemblages on both types of plastic litter versus tile. However, there were no differences among substrates for chlorophyll, respiration, and the abundance and diversity of algal and fungal assemblages. Thus, we concluded that the primary driver of biofilm metabolism and community composition were site characteristics, rather than substrate type. Additional studies are needed to quantify which site-specific characteristics drive biofilm dynamics on plastic litter in streams (e.g., water chemistry, light, seasonality, hydrology). These results add to the growing literature on the biofilm 'plastisphere' in aquatic ecosystems, demonstrating that the factors which control the assembly and activity of biofilm communities on plastic substrates (including bacteria, algal, and fungal assemblages together) in urban streams are similar to those driving biofilm dynamics on natural substrates.


Assuntos
Plásticos , Rios , Bactérias , Biofilmes , Clorofila A , Ecossistema , Poliestirenos
5.
J Mol Med (Berl) ; 97(5): 723-736, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30918989

RESUMO

Pannexins (Panxs), large-pore channel forming glycoproteins, are expressed in a wide variety of tissues including the skin, bone, and cochlea. To date, the use of single knock-out mouse models of both Panx1 and Panx3 have demonstrated their roles in skin development, bone formation, and auditory phenotypes. Due to sequence homology between Panx1 and Panx3, when one Panx is ablated from germline, the other may be upregulated in a compensatory mechanism to maintain tissue homeostasis and function. To evaluate the roles of Panx1 and Panx3 in the skin, bone, and cochlea, we created the first Panx1/Panx3 double knock-out mouse model (dKO). These mice had smaller litters and reduced body weight compared to wildtype controls. The dKO dorsal skin had decreased epidermal and dermal area as well as decreased hypodermal area in neonatal but not in older mice. In addition, mouse skull shape and size were altered, and long bone length was decreased in neonatal dKO mice. Finally, auditory tests revealed that dKO mice did not exhibit hearing loss and were even slightly protected against noise-induced hearing damage at mid-frequency regions. Taken together, our findings suggest that Panx1 and Panx3 are important at early stages of development in the skin and bone but may be redundant in the auditory system. KEY MESSAGES: Panx double KO mice had smaller litters and reduced body weight. dKO skin had decreased epidermal and dermal area in neonatal mice. Skull shape and size changed plus long bone length decreased in neonatal dKO mice. dKO had no hearing loss and were slightly protected against noise-induced damage.


Assuntos
Desenvolvimento Ósseo , Cóclea/crescimento & desenvolvimento , Conexinas/genética , Deleção de Genes , Proteínas do Tecido Nervoso/genética , Pele/crescimento & desenvolvimento , Animais , Osso e Ossos/metabolismo , Cóclea/metabolismo , Audição , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pele/metabolismo
6.
Sci Rep ; 8(1): 11639, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30076314

RESUMO

Microplastic is a contaminant of concern worldwide. Rivers are implicated as major pathways of microplastic transport to marine and lake ecosystems, and microplastic ingestion by freshwater biota is a risk associated with microplastic contamination, but there is little research on microplastic ecology within freshwater ecosystems. Microplastic uptake by fish is likely affected by environmental microplastic abundance and aspects of fish ecology, but these relationships have rarely been addressed. We measured the abundance and composition of microplastic in fish and surface waters from 3 major tributaries of Lake Michigan, USA. Microplastic was detected in fish and surface waters from all 3 sites, but there was no correlation between microplastic concentrations in fish and surface waters. Rather, there was a significant effect of functional feeding group on microplastic concentration in fish. Neogobius melanostomus (round goby, a zoobenthivore) had the highest concentration of gut microplastic (19 particles fish-1) compared to 10 other fish taxa measured, and had a positive linear relationship between body size and number of microplastic particles. Surface water microplastic concentrations were lowest in the most northern, forested watershed, and highest in the most southern, agriculturally dominated watershed. Results suggest microplastic pollution is common in river food webs and is connected to species feeding characteristics. Future research should focus on understanding the movement of microplastic from point-source and diffuse sources and into aquatic ecosystems, which will support pollution management efforts on inland waters.


Assuntos
Ecossistema , Peixes/fisiologia , Plásticos/efeitos adversos , Poluentes Químicos da Água/toxicidade , Animais , Monitoramento Ambiental , Água Doce/química , Humanos , Lagos/química , Rios/química
7.
Curr Biol ; 9(10): 522-9, 1999 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-10339425

RESUMO

BACKGROUND: The protein kinase C (PKC) family has been implicated in the control of many cellular functions. Although PKC isotypes are characterized by their allosteric activation, phosphorylation also plays a key role in controlling activity. In classical PKC isotypes, one of the three critical sites is a carboxy-terminal hydrophobic site also conserved in other AGC kinase subfamily members. Although this site is crucial to the control of this class of enzymes, the upstream kinase(s) has not been identified. RESULTS: A membrane-associated kinase activity that phosphorylates the hydrophobic site in PKCalpha was detected. This activity was suppressed when cells were pretreated with the immunosuppresant drug rapamycin or the phosphoinositide (Pl) 3-kinase inhibitor LY294002. These pretreatments also blocked specifically the serum-induced phosphorylation of the hydrophobic site in PKCdelta in vivo. The most highly purified hydrophobic site kinase preparations ( approximately 10,000-fold) reacted with antibodies to PKCzeta/iota. Consistent with this, rapamycin and LY294002 reduced the recovery of PKCzeta from the membrane fraction of transfected cells. An activated mutant of PKCzeta, but not wild-type PKCzeta, induced phosphorylation of the PKCdelta hydrophobic site in a rapamycin-independent manner, whereas a kinase-dead PKCzeta mutant suppressed this serum-induced phosphorylation. The immunopurified, activated mutant of PKCzeta could phosphorylate the PKCdelta hydrophobic site in vitro, whereas wild-type PKCzeta could not. CONCLUSIONS: PKCzeta is identified as a component of the upstream kinase responsible for the phosphorylation of the PKCdelta hydrophobic site in vitro and in vivo. PKCzeta can therefore control the phosphorylation of this PKCdelta site, antagonizing a rapamycin-sensitive pathway.


Assuntos
Proteína Quinase C/metabolismo , Sirolimo/farmacologia , Animais , Sítios de Ligação , Linhagem Celular , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteína Quinase C/química , Ratos , Serina/metabolismo , Especificidade por Substrato
8.
J Gastrointest Surg ; 21(4): 614-621, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28120276

RESUMO

BACKGROUND: Enhanced recovery programmes improve outcomes in surgery, but their implementation after upper gastrointestinal resection has been limited. The aim of this study was to compare short-term outcomes for patients undergoing oesophagogastric surgery in an enhanced recovery programme (EROS). METHODS: EROS was developed after a multidisciplinary meeting by multiple rounds of revision. EROS was applied to all patients undergoing major upper GI resection at a university teaching hospital in the UK from 20/9/13, with data reviewed at 18/09/15. EROS was assessed to identify predictors for compliance. RESULTS: One hundred six patients underwent major upper GI resection including 81 oesophagectomies, 24 gastrectomies and 1 colonic interposition graft. Major complications (Clavien Dindo ≥3) occurred in 12 patients with 1 in-hospital death. Thirty-five patients (44%) were discharged on target day 8 of the EROS programme. Age and complications were independently associated with missing this discharge target. CONCLUSION: Enhanced recovery is feasible and safe after major upper gastrointestinal surgery.


Assuntos
Esofagectomia , Gastrectomia , Assistência Perioperatória/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colo/transplante , Deambulação Precoce , Esofagectomia/efeitos adversos , Feminino , Gastrectomia/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Desenvolvimento de Programas , Resultado do Tratamento
9.
J Hum Hypertens ; 29(12): 737-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25810066

RESUMO

There is evidence implicating abnormalities in the nitric oxide (NO) pathway in the development of glucocorticoid-induced hypertension (GC-HT). In humans, a reduction in NO availability during cortisol treatment has been observed. This study examined whether the NO donation may reverse the elevated blood pressure (BP) observed with cortisol treatment. A randomised double-blind, placebo-controlled, crossover study was undertaken in eight healthy men to address the effect of co-administration of isosorbide mononitrate (ISMN, 60 mg single dose, day 5) with cortisol (200 mg per day, days 1-6) and then compared with placebo (single dose, day 5) with cortisol. After a 2-week washout period, subjects crossed over to the alternate treatment. BP measurements were obtained using a mercury sphygmomanometer. Tonometry was used to estimate central pressures. There was a significant rise in mean arterial pressure with cortisol: 80 ± 3 vs 89 ± 3 mm Hg (day 1 vs day 5, cortisol+ISMN phase, P < 0.001) and 81 ± 3 vs 89 ± 3 mm Hg (day 1 vs day 5, cortisol+placebo phase, P < 0.01). ISMN significantly decreased aortic augmentation index: -17.3 ± 3.2 vs 1.8 ± 3.5%, (differences calculated from day 5-day 1, cortisol/ISMN vs cortisol+placebo, P < 0.001). These results demonstrated that GC-HT can be modified by co-administration of exogenous NO donors, consistent with the hypothesis that GC-HT is accompanied by reduced NO activity in humans.


Assuntos
Anti-Inflamatórios/efeitos adversos , Hidrocortisona/efeitos adversos , Hipertensão/tratamento farmacológico , Dinitrato de Isossorbida/análogos & derivados , Doadores de Óxido Nítrico/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Peso Corporal/efeitos dos fármacos , Estudos Cross-Over , Preparações de Ação Retardada , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Dinitrato de Isossorbida/farmacologia , Dinitrato de Isossorbida/uso terapêutico , Masculino , Nitratos/sangue , Doadores de Óxido Nítrico/farmacologia , Nitritos/sangue , Adulto Jovem
10.
J Clin Endocrinol Metab ; 78(2): 381-6, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8106626

RESUMO

To investigate whether GH is a regulator of body composition and energy metabolism in adult life, we have compared body composition and resting energy expenditure (REE) in a cross-sectional study in 20 acromegalic and 20 normal subjects, pair-matched for sex, age, height, and weight. In a longitudinal study, 8 acromegalic patients were also studied before and after 12 weeks of treatment [n = 6 during octreotide (100 micrograms, 3 times/day); n = 2 after pituitary surgery], and 7 patients were studied 12 weeks after withdrawal of octreotide. REE was measured by indirect calorimetry and fat mass and fat-free soft tissue mass (FFSTM) by dual energy x-ray absorptiometry. A subgroup of 12 matched pairs of subjects and 7 treated patients had measurement of extracellular water (ECW) by 24Na dilution, which when subtracted from FFSTM provided an estimate of body cell mass (BCM). Fat mass was significantly reduced (25.4 +/- 2.2 vs. 29.7 +/- 2.7 kg; P = 0.007) and FFSTM increased (53.3 +/- 2.2 vs. 49.2 +/- 2.3 kg; P = 0.003) in acromegaly with ECW (25.6 +/- 1.6 vs. 21.1 +/- 0.9 L; P = 0.0003), but not BCM, significantly elevated. Treatment of acromegaly increased fat mass and reduced FFSTM [change (delta), -1.3 +/- 0.4 kg; P = 0.004]; the latter reflected a significant fall in ECW (delta, -2.2 +/- 0.4 L; P = 0.002), but not BCM. The opposite effect on body composition occurred after treatment withdrawal. REE was increased in acromegaly (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P = 0.02) and significantly related to insulin-like growth factor-I (P = 0.02). REE was significantly reduced (delta, -154 +/- 17 Cal/24 h; P = 0.0001) with treatment and increased after treatment withdrawal (P = 0.003). In acromegaly, there is a reversible 1) reduction in fat mass; 2) increase in FFSTM, accounted for by an increase in ECW, but not BCM; and 3) increase in REE, which is dependent on disease activity. We conclude from these observations in acromegaly that GH is a regulator of energy metabolism and body composition.


Assuntos
Acromegalia/metabolismo , Acromegalia/fisiopatologia , Composição Corporal/fisiologia , Metabolismo Energético/fisiologia , Absorciometria de Fóton , Acromegalia/epidemiologia , Adulto , Idoso , Estatura/fisiologia , Peso Corporal/fisiologia , Calorimetria , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Octreotida/farmacologia , Radioimunoensaio , Descanso/fisiologia
11.
J Clin Endocrinol Metab ; 80(2): 486-91, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7852509

RESUMO

Short term GH administration increases lipid breakdown and oxidation (lipidox) and reduces glucose uptake and carbohydrate oxidation (CHOox). It is not clear whether similar shifts in substrate oxidation occur in acromegaly, and our aim was to investigate this. Using indirect calorimetry, we compared energy expenditure, CHOox, and lipidox in 20 acromegalic patients and 20 normal subjects pair-matched for sex, age, height, and weight. Investigations were performed in the basal state (12-h fast) and during a 75-g oral glucose tolerance test (OGTT). Acromegalic patients had significantly higher fasting glucose levels and greater glucose and insulin responses during an OGTT than normal subjects. Fasting nonesterified free fatty acid and insulin-like growth factor (IGF)-binding protein-1 levels were similar in the two groups, and both were acutely suppressed by oral glucose to the same degree. Basal energy expenditure was significantly greater in the acromegalic patients (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P < 0.05), who showed a trend toward higher basal CHOox. Oral glucose resulted in a significantly higher rise in energy expenditure in the normal compared to the acromegalic subjects. During the OGTT, CHOox significantly increased in both groups, but rose to a higher level in the acromegalic patients (177 +/- 10 vs. 138 +/- 9 mg/min; P = 0.004). Oral glucose significantly reduced lipidox in both groups, but lipidox was reduced to a significantly lower level in the acromegalic patients (32 +/- 4 vs. 46 +/- 3 mg/min; P = 0.004). In acromegaly, basal CHOox (r = 0.56; P = 0.01) and postglucose CHOox (r = 0.79; P = 0.0001) were both positively correlated to IGF-I, but not to insulin and/or glucose. In normal subjects, postglucose CHOox was positively correlated to IGF-I. In summary, hyperinsulinemia in acromegaly was associated with higher glucose levels and a blunted thermogenic response to glucose, and displayed no relationship to the pattern of substrate oxidation. CHOox was increased, and lipidox was reduced in acromegaly, and the extent of IGF-I elevation was related to CHOox in the basal and postglucose states. We conclude that 1) the chronic effects of GH excess on substrate oxidation differ from the short term effects of GH administration; 2) impaired insulin action in acromegaly extends to effects on energy expenditure; and 3) IGF-I may be an important regulator of substrate oxidation in acromegaly.


Assuntos
Acromegalia/metabolismo , Metabolismo dos Carboidratos , Metabolismo Energético , Metabolismo dos Lipídeos , Administração Oral , Adulto , Idoso , Calorimetria Indireta , Estudos Transversais , Metabolismo Energético/efeitos dos fármacos , Feminino , Glucose/farmacologia , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos
12.
J Comp Neurol ; 432(2): 259-67, 2001 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-11241390

RESUMO

The developing brain is exquisitely sensitive to gonadal steroid hormones, which permanently differentiate the neural substrate during a critical developmental period. One of the more striking sexual dimorphisms in the adult rat brain is synaptic patterning in the arcuate nucleus (ARC); females have twice the number of axospinous synapses as males (Matsumoto and Arai [1980] Brain Res. 190:238-242). Previously, we have demonstrated that a similar dimorphism in spine densities on ARC dendrites is present as early as early as postnatal day 2 (PN2) in Golgi-impregnated rat brains (Mong et al. [1999] J. Neurosci. 19:1464-1472). Males have 37% fewer dendritic spines than females. Moreover, these spine densities are sensitive to changes in the hormonal milieu such that males castrated on the day of birth have a significant increase in spine density, whereas females masculinized at birth by gonadal steroid exposure have a decreased dendritic spine density. One of the limitations of the Golgi technique is the inability to confirm the presence of synapses. The current study used quantitative electron microscopy and demonstrated that testosterone exposure dramatically reduced axospinous synapses in the ARC by PN 2. Males had 54% fewer and masculinized females had 77% fewer axospinous synapses than females (P < 0.05 and P < 0.01, respectively). We previously reported that gonadal steroids induce coincident changes in neuronal and astrocyte morphology in the neonatal ARC (Mong et al., 1999), and here confirm that these changes include an altered synaptic pattern that is strikingly similar to that observed in the adult (Matsumoto and Arai, 1980).


Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Axônios/efeitos dos fármacos , Dendritos/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Sinapses/efeitos dos fármacos , Testosterona/farmacologia , Animais , Animais Recém-Nascidos , Núcleo Arqueado do Hipotálamo/crescimento & desenvolvimento , Axônios/fisiologia , Axônios/ultraestrutura , Dendritos/fisiologia , Dendritos/ultraestrutura , Feminino , Masculino , Neurópilo/efeitos dos fármacos , Neurópilo/fisiologia , Neurópilo/ultraestrutura , Gravidez , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Sinapses/fisiologia , Sinapses/ultraestrutura
13.
Arch Neurol ; 37(3): 160-4, 1980 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7356423

RESUMO

Electromyographic data were analyzed in a retrospective study of 16 patients with idiopathic brachial plexus neuropathy (BPN) and 15 patients with secondary BPN. In both groups, abnormalities on sensory and musculocutaneous motor conduction studies and lack of paraspinal fibrillation potentials on needle examination seemed most helpful in localizing a lesion to the brachial plexus. Routine motor conduction studies (distal and proximal ulnar and median) and F-wave latencies were less helpful.


Assuntos
Plexo Braquial/fisiopatologia , Atrofia Muscular/fisiopatologia , Neuralgia/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Eletromiografia , Dedos/inervação , Humanos , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Músculos/inervação , Atrofia Muscular/diagnóstico , Condução Nervosa , Neuralgia/diagnóstico , Nervo Ulnar/fisiopatologia
14.
Arch Neurol ; 45(12): 1355-9, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2461693

RESUMO

We studied ten patients with IgM monoclonal gammopathies. Five had M proteins that reacted with myelin-associated glycoprotein (MAG) and five had no recognizable antinerve activity. The neuropathy in the MAG-reactive patients was homogeneous by clinical and laboratory analysis, while the neuropathy in the MAG-nonreactive patients varied considerably. Both groups responded well to immunosuppressive therapy, which lowered the concentration of the serum M protein. The homogeneity of the MAG-reactive patients and their response to sustained lowering of the M protein levels support the concept that the IgM M protein directly damages nerve fibers and is the proximate cause of the polyneuropathy.


Assuntos
Imunoglobulina M , Paraproteinemias/complicações , Doenças do Sistema Nervoso Periférico/complicações , Idoso , Feminino , Humanos , Imunoglobulina M/análise , Leucemia Linfocítica Crônica de Células B/complicações , Masculino , Pessoa de Meia-Idade , Proteínas da Mielina/imunologia , Glicoproteína Associada a Mielina , Paraproteinemias/fisiopatologia , Paraproteinemias/terapia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/terapia
15.
Cancer Epidemiol Biomarkers Prev ; 5(9): 749-51, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8877067

RESUMO

Five-year average annual age-adjusted cancer incidence rates for Alaska Natives (Eskimos, Indians, and Aleuts) for the most recent period (1989-1993) are compared to rates of 20 years earlier. Rates for all cancers combined increased 28 and 25% in men and women, respectively, during the 25-year interval. Increases were seen in men in cancers of the lung, prostate, and colon and in women for cancers of the lung, breast, and corpus uteri. Rates are also compared to data from the the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for United States whites. Rates for all cancers combined in Alaska Native women are now similar to those of United States whites, whereas rates in Alaska Native men are lower than the United States, but only 10% lower. Significant site-specific differences previously reported between Alaska Natives and United States whites persist.


Assuntos
Indígenas Norte-Americanos/estatística & dados numéricos , Inuíte/estatística & dados numéricos , Neoplasias/epidemiologia , Alaska/epidemiologia , Povo Asiático , Neoplasias da Mama/epidemiologia , Neoplasias do Colo/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Neoplasias da Próstata/epidemiologia , Programa de SEER , Fatores Sexuais , Estados Unidos/epidemiologia , Neoplasias Uterinas/epidemiologia , População Branca
16.
Neurology ; 43(7): 1304-8, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8327128

RESUMO

We evaluated the clinical characteristics and electromyographic features of 39 patients with monoclonal gammopathy of undetermined significance (MGUS) and neuropathy. Twenty-three patients had a monoclonal IgM protein, 13 had an IgG, and three had an IgA. In 15 patients of the IgM group, the M protein reacted with myelin-associated glycoprotein (MAG). Comparing IgM-MGUS and IgG-MGUS neuropathies, we found the following differences: (1) There was a statistically significant higher frequency of sensory loss in the IgM group. (2) Nine attributes of nerve conduction abnormality were statistically worse in the IgM group, with slowing of conduction velocities and prolonged distal latencies. (3) The frequency of monoclonal IgM was overrepresented in the MGUS neuropathy group. In general, the clinical and electrophysiologic features of the IgM-MGUS MAG-reactive group were not significantly different than the MAG-nonreactive group. Our cases are similar to those previously reported and suggest that monoclonal IgM-MGUS should be separated conceptually from monoclonal IgG neuropathies.


Assuntos
Doenças do Sistema Nervoso/imunologia , Paraproteinemias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletromiografia , Feminino , Humanos , Imunoglobulina G/fisiologia , Imunoglobulina M/fisiologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/fisiopatologia , Condução Nervosa/fisiologia , Paraproteinemias/fisiopatologia , Tempo de Reação/fisiologia , Estudos Retrospectivos
17.
Neurology ; 42(8): 1625-7, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1641161

RESUMO

We describe four patients with a neuromuscular syndrome characterized by relatively isolated neck extensor weakness. EMG and muscle biopsies suggest a restrictive noninflammatory myopathy predominantly affecting the cervical paraspinal muscles.


Assuntos
Músculos do Pescoço/inervação , Doenças Neuromusculares/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Eletromiografia , Feminino , Cabeça , Humanos , Pessoa de Meia-Idade , Músculos do Pescoço/patologia , Músculos do Pescoço/fisiopatologia , Doenças Neuromusculares/patologia , Síndrome
18.
Neurology ; 41(1): 131-4, 1991 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1985278

RESUMO

We report a woman with Guillain-Barré syndrome who developed a flexion posture of the right arm and hand resembling upper motor neuron dysfunction. EMG demonstrated that involuntary peripherally generated continuous motor unit discharges caused the posture.


Assuntos
Espasticidade Muscular/etiologia , Polirradiculoneuropatia/complicações , Idoso , Extremidades , Feminino , Humanos , Neurônios Motores/fisiologia , Rigidez Muscular , Músculos/inervação , Condução Nervosa , Polirradiculoneuropatia/fisiopatologia , Postura , Recrutamento Neurofisiológico , Sensação , Fatores de Tempo
19.
Neurology ; 29(5): 662-9, 1979 May.
Artigo em Inglês | MEDLINE | ID: mdl-571564

RESUMO

Two patients had bilateral facial myokymia in association with polyradiculoneuropathy. Characteristic electromyographic findings allow polyradiculoneuropathy to be differentiated from other causes of facial movements, and support the possibility that extraaxial facial nerve involvement is another cause of facial myokymia.


Assuntos
Músculos Faciais/fisiopatologia , Paralisia Facial/fisiopatologia , Polirradiculoneuropatia/fisiopatologia , Adulto , Nervo Facial/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Condução Nervosa , Parestesia/fisiopatologia , Nervo Fibular/fisiopatologia , Nervo Tibial/fisiopatologia , Nervo Ulnar/fisiopatologia
20.
Neurology ; 38(10): 1635-7, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3419609

RESUMO

A 67-year-old woman developed a fixed, flexed posture of the right arm and hand due to a cervical astrocytoma. EMG showed continuous motor unit potential firing at 8 to 15 Hz with an abnormal silent period, presumably due to the loss of local spinal cord inhibitory interneuronal input.


Assuntos
Astrocitoma/complicações , Rigidez Muscular/etiologia , Neoplasias da Medula Espinal/complicações , Potenciais de Ação , Idoso , Animais , Braço , Feminino , Humanos , Rigidez Muscular/fisiopatologia
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