RESUMO
Critically ill patients are hypercatabolic due to stress and inflammation. This condition induces hyperglycemia. Muscle wasting is intense during critical illness. Its prevention is essential. This is possible by early and appropriate nutritional support. Preserving the function of the gastrointestinal tract with enteral nutrition is the gold standard. However, when targeted protein-caloric intake is not met through enteral nutrition within the first three days in the intensive care unit (ICU), supplemental parenteral nutrition is administered to reduce morbidity and mortality. In addition, in order to limit metabolic imbalance and reduce mortality, glycemic control using insulin therapy is mandatory. This article reviews the current understanding of parenteral nutrition and insulin therapy in ICU patients, and provides the decision model applied in our institution.
Assuntos
Cuidados Críticos/métodos , Hiperglicemia/terapia , Insulina/uso terapêutico , Nutrição Parenteral/métodos , Glicemia/metabolismo , Estado Terminal/terapia , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Resistência à Insulina , Prática Profissional , Estresse Fisiológico/fisiologiaRESUMO
The refeeding syndrome is frequent and potentially deadly, still it is underdiagnosed. It is defined by clinical and biological manifestations that are seen upon refeeding of malnourished patients. It is the consequence of the transition from catabolism to anabolism. Ions intracellular shift caused by insulin and B1 vitamin deficiency are fundamental in the development of this syndrome. Riskconditions are well summarized by the NICE criteria. To avoid refeeding syndrome, it is fundamental to find and correct any electrolytic deficiency and to give thiamine before starting a slow and progressive oral, enteral or parenteral refeeding.
Assuntos
Nutrição Enteral/métodos , Nutrição Parenteral/métodos , Síndrome da Realimentação/fisiopatologia , Humanos , Insulina/metabolismo , Síndrome da Realimentação/diagnóstico , Síndrome da Realimentação/terapia , Fatores de Risco , Tiamina/administração & dosagem , Deficiência de Tiamina/complicaçõesRESUMO
Androgen deprivation is a therapeutic option for patients with prostate cancer, however with a range of side effects that negatively affects their physical and psychological condition. A multidisciplinary care program, ADAPP ("Androgenic deprivation in prostate cancer patients"), has been created with a special focus on managing these side effects. This article describes the intervention of the liaison psychiatry within this program, with care options ranging from psychological support to intensive psychotherapy to address patients' intrapsychic dynamics throughout this care program. Clinical cases are reported to illustrate the relevance and the necessity of this specialized counselling.
Assuntos
Antagonistas de Androgênios/administração & dosagem , Aconselhamento , Equipe de Assistência ao Paciente , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Aconselhamento/métodos , Depressão/induzido quimicamente , Depressão/prevenção & controle , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/prevenção & controle , Fadiga/induzido quimicamente , Fadiga/prevenção & controle , Humanos , Comunicação Interdisciplinar , Libido/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Neoplasias da Próstata/tratamento farmacológico , Psicoterapia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/prevenção & controle , Resultado do TratamentoRESUMO
When enteral nutrition is indicated to prevent or to treat a patient with denutrition choosing between a nasogastric tube (NGT) and a percutaneous endoscopic gastrostomy (PEG) is not always an easy decision. In neurological patients with swallowing disturbances or in patients with head and neck tumors, PEG is associated with lower rates of feeding tube dislodgement, while NGT has lower rates or morbidity. A meta-analysis showed that the interruption of nutrition is less frequent with PEG but there is no difference in terms of mortality and aspiration pneumonia between PEG and NGT. The European Society for Clinical Nutrition and Metabolism recommends PEG when enteral nutrition is expected to last more than 3 weeks.
Assuntos
Nutrição Enteral/métodos , Gastrostomia/métodos , Intubação Gastrointestinal , Humanos , Metanálise como AssuntoRESUMO
Muscular wasting is frequently encountered in COPD patients and is related to a decrease in exercise tolerance, a higher morbidity and mortality. One of the potential causes isa low serum testosterone, which is frequent in COPD. Various studies have explored the effect of testosterone administration alone or as part of combined pulmonary rehabilitation and nutrition protocols. Testosterone had a positive impact on muscle mass and force, and to a lesser extent on physical endurance and respiratory parameters. Future studies should better define appropriate dosage and treatment duration. In the meantime, testosterone should be administered to COPD patients with overt hypogonadism, or in multidisciplinary specialized programmes.
Assuntos
Androgênios/uso terapêutico , Atrofia Muscular/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Testosterona/uso terapêutico , Androgênios/efeitos adversos , Androgênios/sangue , Tolerância ao Exercício , Humanos , Atrofia Muscular/etiologia , Resistência Física/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testosterona/efeitos adversos , Testosterona/sangueRESUMO
Reduced total body protein mass is a marker of protein-energy malnutrition and has been associated with numerous complications. Severe illness is characterized by a loss of total body protein mass, mainly from the skeletal muscle. Studies on protein turnover describe an increased protein breakdown and, to a lesser extent, an increased whole-body protein synthesis, as well as an increased flux of amino acids from the periphery to the liver. Appropriate nutrition could limit protein catabolism. Nutritional support limits but does not stop the loss of total body protein mass occurring in acute severe illness. Its impact on protein kinetics is so far controversial, probably due to the various methodologies and characteristics of nutritional support used in the studies. Maintaining calorie balance alone the days after an insult does not clearly lead to an improved clinical outcome. In contrast, protein intakes between 1.2 and 1.5 g/kg body weight/day with neutral energy balance minimize total body protein mass loss. Glutamine and possibly leucine may improve clinical outcome, but it is unclear whether these benefits occur through an impact on total body protein mass and its turnover, or through other mechanisms. Present recommendations suggest providing 20 - 25 kcal/kg/day over the first 72 - 96 hours and increasing energy intake to target thereafter. Simultaneously, protein intake should be between 1.2 and 1.5 g/kg/day. Enteral immunonutrition enriched with arginine, nucleotides, and omega-3 fatty acids is indicated in patients with trauma, acute respiratory distress syndrome (ARDS), and mild sepsis. Glutamine (0.2 - 0.4 g/kg/day of L-glutamine) should be added to enteral nutrition in burn and trauma patients (ESPEN guidelines 2006) and to parenteral nutrition, in the form of dipeptides, in intensive care unit (ICU) patients in general (ESPEN guidelines 2009).
Assuntos
Estado Terminal , Proteínas Alimentares/administração & dosagem , Necessidades Nutricionais , Proteínas/metabolismo , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Composição Corporal , Proteínas Alimentares/metabolismo , Proteínas Alimentares/uso terapêutico , Ingestão de Energia , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Guias de Prática Clínica como Assunto , Biossíntese de Proteínas , Estresse Psicológico/dietoterapia , Estresse Psicológico/metabolismoRESUMO
BACKGROUND: Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) score is frequently used for screening the sarcopenia risk in older people. However, the agreement between SARC-F and loss of ultrasound-derived muscle thickness in hospitalized older cancer patients is unexplored. OBJECTIVE: The primary objective was to evaluate the relationship between the SARC-F score and ultrasound-derived muscle thickness of rectus femoris and vastus intermedius in older hospitalised cancer patients. The secondary objective was to identify the presence of sarcopenia. MEASUREMENTS: A cross-sectional study enrolled forty-one older hospitalised cancer patients ongoing chemotherapy or surgical treatment. Body weight (kg) was measured using a digital scale and height using a portable stadiometer to assess body mass index. SARC-F was performed to assess and classify sarcopenia risk (with (SARC-F: ≥4), without (SARC-F: <4). US-derived muscle thickness of rectus femoris and vastus intermedius was assessed using a portable ultrasound. Relationship between the SARC-F and muscle thickness was tested using Pearson´s correlation and Bland-Altman analyses. RESULTS: Approximately, 46.3% of the patients presented sarcopenia and a lower non-significant muscle thickness of rectus femoris and vastus intermedius (SARC-F ≥4: 18.54±6.28 vs. SARC-F <4: 22.22±9.16 mm, p=0.07). There was a moderate negative correlation between SARC-F and muscle thickness (r=-0.40, p=0.004). Additionally, Bland-Altman plots no found systematic bias risk between SARC-F and ultrasound-derived muscle thickness. CONCLUSIONS: Approximately, 46.3% of older hospitalized cancer patients presented sarcopenia. Additionally, we found a moderate inverse correlation and no systematic bias risk between SARC-F and ultrasound-measured muscle thickness.
Assuntos
Sarcopenia/diagnóstico , Coxa da Perna/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Breast cancer (BC) is one of the most important problems of public health. Among the avoidable risk factors during a woman's life, overweight and obesity are very important ones. Furthermore they are increasing worldwide. The risk of breast cancer is traditionally linked to obesity in postmenopausal women; conversely, it is neutral or even protective in premenopausal women. Since the initiator and promoter factors for BC act over a long time, it seems unlikely that the menopausal transition may have too big an impact on the role of obesity in the magnitude of the risk. We reviewed the literature in an attempt to understand this paradox, with particular attention to the body fat distribution and its impact on insulin resistance. The association of insulin resistance and obesity with BC risk are biologically plausible and consistent. Estradiol (E2) and IGFs act as mitogens in breast cancer cells. They act together and reciprocally. However the clinical and biological methods to assess the impact of insulin resistance are not always accurate. Furthermore insulin resistance is far from being a constant feature in obesity, particularly in premenopausal women; this complicates the analysis and explains the discrepancies in large prospective trials. The most consistent clinical feature to assess risk across epidemiological studies seems to be weight gain during lifetime. Loss of weight is associated with a lower risk for postmenopausal BC compared with weight maintenance. This observation should be an encouragement for women since loss of weight may be an effective strategy for breast cancer risk reduction.
Assuntos
Neoplasias da Mama/epidemiologia , Resistência à Insulina/fisiologia , Obesidade/fisiopatologia , Adipocinas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
31P nuclear magnetic resonance (NMR) spectroscopy in vivo and fluorometry were used to measure muscle ATP, total creatine, pH, and Mg2+ in vivo; and to calculate creatine phosphate (CrP), the ratios of CrP/inorganic phosphate (Pi), CrP/ATP, free ADP levels, and the free-energy change in ATP hydrolysis so nutritional effects could be ascertained. These parameters were determined in vivo in resting control, 2-d-fasted, and hypocalorically fed rats and in animals similarly hypocalorically fed and then refed. The ATP, Pi, and intracellular Mg2+ levels were comparable in the four groups. When the fasted and underfed animals were compared with the control and refed animals, there were falls in the ratios of CrP/Pi and CrP/ATP, in the calculated CrP, and the free-energy change of ATP hydrolysis, but a rise in the calculated free ADP. In the hypocaloric group, intracellular pH fell significantly and a large peak was noted in the phosphodiester region. The data are consistent with the hypothesis that ATP levels are maintained at the cost of CrP, suggesting that ATP production is disturbed by aerobic and anaerobic mechanisms.
Assuntos
Ingestão de Energia , Jejum , Espectroscopia de Ressonância Magnética , Músculos/fisiologia , Difosfato de Adenosina/análise , Trifosfato de Adenosina/análise , Animais , Bicarbonatos/sangue , Peso Corporal , Dióxido de Carbono/sangue , Creatina/análise , Metabolismo Energético , Cabelo/análise , Concentração de Íons de Hidrogênio , Hidrólise , Magnésio/análise , Masculino , Músculos/análise , Músculos/metabolismo , Pressão Parcial , Fosfatos/análise , Fosfocreatina/análise , Ratos , Ratos Endogâmicos , Pele/análiseRESUMO
Quality of life (QOL) is a concept assessing physical, psychological and social factors which are influencing the patients' well being. Cancer and its therapy induce severe metabolic changes associated with QOL impairment. These alterations contribute to an increased energy wasting and a decreased food intake. Besides, it may lead to tumoral cachexia due to the complex interactions between pro-inflammatory cytokines and the host metabolism. On the other hand, and beyond physical impairments and metabolic effects from cancer, patients often suffer from psychological stress, such as depression. A nutritional intervention should be implemented as soon as cancer is diagnosed. It should be appropriate to the individual needs of the patient, considering the type of oncologic treatment (whether it is curative or palliative), the clinical conditions and the nutritional status. The aim is to reduce or even revert nutritional status impairment, improve the general condition, and subsequently improve quality of life. The primary focus of nutritional intervention accompanying oncologic treatment intended to cure is on the optimization of the balance between energy waste and food intake. Thus trying to achieve further specific purposes such as a decrease of rate of complications and an amelioration of the response and tolerance to the oncologic therapy. The purpose of nutritional support in palliative care is controlling the symptoms related to food intake and delaying the loss of autonomy. And by this means maintaining or improving patients' QOL. It is corraborated by a literature review, that nutritional therapy should form part of the integral oncological support since it contributes considerably to a QOL improvement. Because of the possibility to identify the patients' needs and expectations by assessing their QOL it should be generally included into their nutritional evaluation to be able to tailor the adequate nutritional support.
Assuntos
Neoplasias/dietoterapia , Qualidade de Vida , Humanos , Desnutrição/etiologia , Desnutrição/prevenção & controle , Neoplasias/complicações , Apoio NutricionalRESUMO
BACKGROUND/OBJECTIVES: Greek Orthodox fasting (OF), which involves 180-200 days of fasting per year, is dictated by the Christian Orthodox religion. For the first time, this cross-sectional study examines the characteristics and the effects of OF on anthropometry, cardiometabolic markers and calcium homeostasis in Athonian monks (AMs). SUBJECTS/METHODS: Daily intakes of energy, macro- and micronutrients of a day during a weekend of Nativity Fast, defined as non-restrictive day (NRD), and a weekday during Great Lent, labeled as restrictive day (RD) were recorded. RESULTS: The daily energy intake of 70 AM (age=38.8±9.7 years) was low during both RD and NRD (1265.9±84.5 vs 1660±81 kcal, respectively, P<0.001). Paired samples t-test showed statistically significant difference between daily intakes in RD and NRD: carbohydrates (159.6±21.8 vs 294.3±23.4 g, P<0.0001) and saturated fat (12.7±0.0 vs 16.4±0.0 g, P<0.0001) were lower, whereas protein (89.2±1.3 vs 72.35±1.3 g, P<0.001) was higher during RD. A subsample of 50 monks (age=38.7±10.6 years) formed a study cohort for cardiometabolic and calcium homeostasis assessment. Body weight (74.3±12.9 kg) and body mass index (BMI; 23.8±4.1 kg/m2) were independent of level of physical activity. Optimal profiles for lipid and glucose parameters (total cholesterol: 183.4±41.7 mg/dl, LDL: 120.6±37.6 mg/dl, triglycerides: 72.2±31.3 mg/dl, HDL: 48.5±14.2 mg/dl and homeostasis model assessment of insulin resistance (HOMA-IR) 1.02±0.40) were found. Profound hypovitaminosis D (8.8±6.2 ng/ml), high parathyroid hormone (PTH): 115.5±48.0 pg/ml with normal serum calcium levels (8.9±3.2 mg/dl) was observed. CONCLUSIONS: Unaffected by variation in lifestyle factors, the results of this unique study offers clear evidence for the health benefits of the strict Athonian OF through optimal lipid and glucose homeostasis.
Assuntos
Ortodoxia Oriental , Jejum , Monges , Adulto , Antropometria , Biomarcadores/sangue , Índice de Massa Corporal , Colesterol/sangue , Estudos Transversais , Dieta Mediterrânea , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Proteínas Alimentares , Exercício Físico , Grécia , Humanos , Estilo de Vida , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support.
Assuntos
Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Resistência à Insulina , Política Nutricional , Apoio Nutricional , Glicemia/metabolismo , Metabolismo dos Carboidratos , Dieta , Medicina Baseada em Evidências , Índice Glicêmico , Humanos , Hiperglicemia/etiologia , Hiperglicemia/terapia , Hipoglicemia/etiologia , Hipoglicemia/terapia , Itália , Necessidades Nutricionais , Fatores de Risco , Sociedades CientíficasRESUMO
The ESPEN guidelines on enteral nutrition are the first evidence-based European recommendations for enteral nutrition. They were established by European experts for a variety of disease groups. During guideline development it became evident that terms and definitions in clinical nutrition have been used inconsistently depending on medical disciplines as well as regional and personal preferences. Therefore, to increase explanatory accuracy it was necessary to unify them. In this chapter terms and definitions used throughout all guidelines are explained. Additionally answers to more general questions, which might be important in most indications are dealt with, i.e. use of fibre containing and diabetes formulae.
Assuntos
Nutrição Enteral/normas , Gastroenterologia/normas , Guias de Prática Clínica como Assunto , Terminologia como Assunto , Nutrição Enteral/métodos , Europa (Continente) , Gastroenterologia/métodos , HumanosRESUMO
Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in vivo degradation and low DNA-incorporation rates. We evaluated whether blocking of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuridine (IdUrd). We first show in vitro that coincubation with FdUrd substantially increased incorporation of [125I]IdUrd and [3H]dThd in the three tested human glioblastoma lines. Flow cytometry analysis showed that a short coincubation with FdUrd (1 h) produces a signal increase per labeled cell. We then measured biodistribution 24 h after i.v. injection of [125I]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared with animals given [125I]IdUrd alone, i.v. preadministration for 1 h of 10 mg/kg FdUrd increased the uptake of [125I]IdUrd in the three tumors 4.8-6.8-fold. Compatible with previous reports, there were no side effects in mice observed for 2 months after receiving such a treatment. The tumor uptake of [125I]IdUrd was increased < or =13.6-fold when FdUrd preadministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained lower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bone marrow, spleen, and intestine) and negligible in quiescent tissues. DNA extraction showed that 72-80% of radioactivity in tumor and intestine was bound to DNA. Scintigraphy of xenografted mice was performed at different times after i.v. injection of 3.7 MBq [125I]IdUrd. Tumor detection was significantly improved after FdUrd preadministration while still equivocal after 24 h in mice given [125I]IdUrd alone. Furthermore, background activity could be greatly reduced by p.o. administration of KClO4 in addition to potassium iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radio-IdUrd and possibly other dThd analogues.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Floxuridina/farmacologia , Glioblastoma/diagnóstico por imagem , Idoxuridina , Compostos Radiofarmacêuticos , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Ciclo Celular/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Sinergismo Farmacológico , Floxuridina/toxicidade , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Idoxuridina/farmacocinética , Idoxuridina/toxicidade , Radioisótopos do Iodo , Masculino , Camundongos , Camundongos Nus , Percloratos/farmacologia , Compostos de Potássio/farmacologia , Cintilografia/métodos , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/toxicidade , Timidina/metabolismo , Distribuição Tecidual , Trítio , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The involvement of human prolactin (hPRL) in breast cancer has been recently reconsidered based on its autocrine/paracrine proliferative effect described in human mammary tumor epithelial cells. Therefore, there is growing interest in the development of potent hPRL antagonists that may inhibit this effect. We previously designed hPRL analogs displaying antagonistic properties in a human transcriptional bioassay. We now report that the most potent of those analogs, G129R-hPRL, antagonizes all hPRL-induced effects analysed in various breast cancer cell lines, including cell proliferation. The analog per se lacks intrinsic agonistic activity on PRL receptor-activated signaling cascades, cell proliferation and apoptosis, indicating that its mode of action only occurs through competitive inhibition of hPRL. We provide some molecular basis of this antagonistic effect by demonstrating that G129R-hPRL competitively inhibits hPRL-activation of the JAK-STAT and MAPK pathways, two signaling cascades involved in the mitogenic effect of hPRL in mammary epithelial cells. This competitive inhibition persists for at least 48 h, as evidenced by long term analysis of STAT5b activation or of progression through cell cycle. These results are the first demonstration at the molecular level that hPRL antagonists interfering with receptor dimerization disrupt signaling events in breast cancer cells, which prevents hPRL-induced cell proliferation.
Assuntos
Comunicação Autócrina/efeitos dos fármacos , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas do Leite , Neoplasias Hormônio-Dependentes/patologia , Prolactina/antagonistas & inibidores , Prolactina/farmacologia , Proteínas Proto-Oncogênicas , Ligação Competitiva , Neoplasias da Mama/genética , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Dimerização , Feminino , Antagonistas de Hormônios/metabolismo , Humanos , Janus Quinase 2 , Neoplasias Hormônio-Dependentes/genética , Prolactina/metabolismo , Prolactina/fisiologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Receptores da Prolactina/agonistas , Receptores da Prolactina/antagonistas & inibidores , Receptores da Prolactina/química , Receptores da Prolactina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Fator de Transcrição STAT1 , Fator de Transcrição STAT3 , Fator de Transcrição STAT5 , Transativadores/antagonistas & inibidores , Transativadores/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Patients with hematological malignancies are well nourished prior to allogeneic hematopoietic stem cell transplantation (HSCT). HSCT and associated complications can affect body composition. The study evaluated cross-sectionally the prevalence and longitudinally the changes in lean body mass index (LBMI) in HSCT patients. Patients (n=82) were classified as normal or low LBMI. Logistic regression analyses were used to estimate odds ratios (OR) for low vs normal LBMI, between healthy volunteers and patients; for limited or extensive vs no chronic graft-versus-host-disease (GVHD); and for decreased (Karnofsky <80) vs normal functional status (>80). Patients were significantly more likely to have low LBMI at 6, 12 months, 2-3, 4-6 and >6 years than volunteers. In all, 38% of patients were below pre-HSCT LBMI at 4-6 years post-HSCT. Low LBMI was significantly associated with steroid treatment (OR 2.6, confidence intervals (CI) 1.3-5.2, P=0.008); limited (OR 5.5, CI 1.7-18.5, P=0.005) or extensive chronic GVHD (OR 20.3, CI 5.7-71.6, P<0.001); and decreased performance status (Karnofsky scores of < or =80) (OR 2.7, CI 1.3-5.9, P=0.01). Patients were more likely to have low LBMI than volunteers. Chronic GVHD and low performance status were associated with low LBMI; thus, complications and/or treatment increase the likelihood of low LBMI.
Assuntos
Composição Corporal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Estudos de Casos e Controles , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Humanos , Avaliação de Estado de Karnofsky , Estudos Longitudinais , Razão de Chances , Estudos Retrospectivos , Esteroides/efeitos adversos , Esteroides/uso terapêutico , Transplante HomólogoRESUMO
Premature ovarian failure occurs in almost 1% of women under age 40. Molecular alterations of the FSH receptor (FSHR) have recently been described. A first homozygous mutation of the FSHR was identified in Finland. More recently, we described two new mutations of the FSHR in a woman presenting a partial FSH-resistance syndrome (patient 1). We now report new molecular alterations of the FSHR in another woman (patient 2) who presented at the age of 19 with primary amenorrhea contrasting with normal pubertal development. She had high plasma FSH, and numerous ovarian follicles up to 3 mm in size were evidenced by ultrasonography. Histological and immunohistochemical examination of ovarian biopsies revealed the presence of a normal follicular development up to the antral stage and disruption at further stages. DNA sequencing showed two heterozygous mutations: Asp224Val in the extracellular domain and Leu601Val in the third extracellular loop of FSHR. Cells transfected with expression vectors encoding the wild type or the mutated Leu601Val receptors bound hormone with similar affinity, whereas binding was barely detectable with the Asp224Val mutant. Confocal microscopy showed the latter to have an impaired targeting to the cell membrane. This was confirmed by its accumulation as a mannose-rich precursor. Adenylate cyclase stimulation by FSH of the Leu601Val mutant receptor showed a 12+/-3% residual activity, whereas in patient 1 a 24+/-4% residual activity was detected for the Arg573Cys mutant receptor. These results are in keeping with the fact that estradiol and inhibin B levels were higher in patient 1 and that stimulation with recombinant FSH did not increase follicular size, estradiol, or inhibin B levels in patient 2 in contrast to what was observed for patient 1. Thus, differences in the residual activity of mutated FSHR led to differences in the clinical, biological, and histological phenotypes of the patient.
Assuntos
Amenorreia/genética , Mutação , Ovário/fisiopatologia , Receptores do FSH/genética , Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Adulto , Amenorreia/tratamento farmacológico , Animais , Células COS/efeitos dos fármacos , Células COS/metabolismo , Feminino , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/uso terapêutico , Inativação Gênica , Humanos , Imuno-Histoquímica , Masculino , Ovário/diagnóstico por imagem , Ovário/patologia , Fenótipo , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/genética , Processamento de Proteína Pós-Traducional , Receptores do FSH/efeitos dos fármacos , Receptores do FSH/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análise de Sequência , UltrassonografiaRESUMO
BACKGROUND: Perioperative nutrition and preoperative oral carbohydrate loading (CHL) have a beneficial impact on the outcomes of gastrointestinal oncological surgery. However no data exists on their effect on morbidly obese patients. OBJECTIVES: Our aim was to establish the short-term and long-term impact of these modalities, notably on metabolically active lean body mass (LBM) - an important factor in maintaining long-term weight loss. METHODS: Patients undergoing laparoscopic Roux-en-Y gastric bypass were randomized to standard management or intervention: CHL drinks consumed 12 and 2 hours presurgery, and immediate postoperative peripheral parenteral nutrition. The primary outcome measured was LBM, measured by Bioelectrical Impedance Analysis (BIA), one and 12 months postsurgery. Secondary outcomes included excess weight loss (EBWL), 30-day complication rate, and length of stay. RESULTS: Of the 203 randomized patients, 198 were included in the analysis. All 101 patients in the control group completed the one-year follow up and 76 completed the BIA. In the intervention group, 93 of 97 patients completed the one-year follow-up and 71 completed the BIA. At one and 12 months follow-up, body composition, LBM, or EBWL were comparable. There was no difference in operative outcomes, complications rates, or length of stay. There was no adverse effect in the intervention group. CONCLUSIONS: In a highly homogeneous group of morbidly obese patients with one-year follow-up, CHL and short-term parenteral nutrition did not lead to significant or sustained LBM preservation or modification in EBWL. There was no significant decrease in complications or length of stay. Our study confirms the safety of these interventions, even in previously unstudied Type 2 diabetic patients.
Assuntos
Cirurgia Bariátrica , Carboidratos/administração & dosagem , Músculo Esquelético/metabolismo , Apoio Nutricional/métodos , Obesidade Mórbida/cirurgia , Assistência Perioperatória/métodos , Redução de Peso/fisiologia , Administração Oral , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Estado Nutricional , Obesidade Mórbida/dietoterapia , Fatores de Tempo , Resultado do TratamentoRESUMO
There are a number of differences between the body composition of children and adults. Body composition measurements in children are inherently challenging, because of the rapid growth-related changes in height, weight, fat-free mass (FFM) and fat mass (FM), but they are fundamental for the quality of the clinical follow-up. All body composition measurements for clinical use are 'indirect' methods based on assumptions that do not hold true in all situations or subjects. The clinician must primarily rely on two-compartment models (that is, FM and FFM) for routine determination of body composition of children. Bioelectrical impedance analysis (BIA) is promising as a bedside method, because of its low cost and ease of use. This paper gives an overview of the differences in body composition between adults and children in order to understand and appreciate the difference in body composition during growth. It further discusses the use and limitations of BIA/bioelectrical spectroscopy (BIA/BIS) in children. Single-frequency and multi-frequency BIA equations must be refined to better reflect the body composition of children of specific ethnicities and ages but will require development and cross-validation. In conclusion, recent studies suggest that BIA-derived body composition and phase angle measurements are valuable to assess nutritional status and growth in children, and may be useful to determine baseline measurements at hospital admission, and to monitor progress of nutrition treatment or change in nutritional status during hospitalization.
Assuntos
Composição Corporal , Desenvolvimento Infantil/fisiologia , Adulto , Estatura , Peso Corporal , Criança , Impedância Elétrica , Humanos , Estado NutricionalRESUMO
OBJECTIVE: To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and omega-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. DESIGN: Six-month prospective randomized double-blind controlled study. SETTING: University hospital outpatient nutrition clinic. PATIENTS: Sixty-four HIV-infected outpatients with CD4 lymphocyte count > or = 10O x 10(6)/l. INTERVENTION: All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g omega-3 fatty acids. MAIN OUTCOME MEASURES: Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. RESULTS: Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. CONCLUSIONS: Enrichment of an oral nutritive supplement with arginine and omega-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.