RESUMEN
Hb Helsinki [HBB: c.248A>T; ß82(EF6)LysâMet] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (ß4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the ß-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.
Asunto(s)
Alelos , Hemoglobinas Anormales/genética , Patrón de Herencia , Mutación , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Globinas beta/genética , Sustitución de Aminoácidos , Análisis Mutacional de ADN , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of our study was to establish an unlabeled probe genotyping approach for rapid detection of the MYD88 L265P mutation in the differential diagnosis of WaldenstrÓ§m macroglobulinemia patients. Analytical and clinical validation of the assay was performed using serially diluted amplicon-cloned standards, 14 clinical bone marrow aspirate samples, and 30 peripheral blood samples from healthy donors, respectively. The analytical validation results showed that the assay is able to reproducibly identify as low as 10% of the L265P mutant. Clinical validation results showed improved detection sensitivity for the L265P mutation compared to Sanger sequencing. With the simplicity, cost-effectiveness, specificity and rapidity, we foresee that the unlabeled probe HRM assay is a good alternative to substitute current established methods for routine diagnostic testing of the MYD88 L265P mutation.
Asunto(s)
Antígenos de Diferenciación/genética , Técnicas de Diagnóstico Molecular/métodos , Sondas de Oligonucleótidos/genética , Macroglobulinemia de Waldenström/diagnóstico , Genotipo , Humanos , Leucina/genética , Técnicas de Diagnóstico Molecular/economía , Mutación , Prolina/genética , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN , Macroglobulinemia de Waldenström/líquido cefalorraquídeo , Macroglobulinemia de Waldenström/genéticaRESUMEN
With advancing age, plasma testosterone levels decline, with free testosterone levels declining more significantly than total testosterone. This fall is thought to underlie the development of physical and mental weakness that occurs with advancing age. In addition, vigorous exercise can also lower total and free testosterone levels with the decline greatest in physically untrained men. The purpose of the study was to evaluate the effect of oral DHEA supplementation, a testosterone precursor, on free testosterone in sedentary middle-aged men during recovery from a high-intensity interval training (HIIT) bout of exercise. A randomized, double-blind, placebo-controlled crossover study was conducted for 8 middle-aged participants (aged 49.3 ± 2.4 years) and an additional 8 young control participants (aged 21.4 ± 0.3 years). Each participant received DHEA (50 mg) and placebo on separate occasions one night (12 h) before a 5-session, 2-min cycling exercise (100% VO2max). While no significant age difference in total testosterone was found, middle-aged participants exhibited significantly lower free testosterone and greater luteinizing hormone (LH) levels than the young control group. Oral DHEA supplementation increased circulating DHEA-S and free testosterone levels well above baseline in the middle-aged group, with no significant effect on total testosterone levels. Total testosterone and DHEA-S dropped significantly until 24 h after HIIT for both age groups, while free testosterone of DHEA-supplemented middle-aged men remained unaffected. These results demonstrate acute oral DHEA supplementation can elevate free testosterone levels in middle-aged men and prevent it from declining during HIIT. Therefore, DHEA supplementation may have significant benefits related to HIIT adaptation.
Asunto(s)
Deshidroepiandrosterona/administración & dosificación , Ejercicio Físico , Testosterona/sangre , Administración Oral , Factores de Edad , Estudios Cruzados , Deshidroepiandrosterona/sangre , Método Doble Ciego , Humanos , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Conducta Sedentaria , Adulto JovenRESUMEN
It is generally thought that topical cooling can interfere with blood perfusion and may have positive effects on recovery from a traumatic challenge. This study examined the influence of topical cooling on muscle damage markers and hemodynamic changes during recovery from eccentric exercise. Eleven male subjects (age 20.2 ± 0.3 years) performed 6 sets of elbow extension at 85% maximum voluntary load and randomly assigned to topical cooling or sham groups during recovery in a randomized crossover fashion. Cold packs were applied to exercised muscle for 15 minutes at 0, 3, 24, 48, and 72 hours after exercise. The exercise significantly elevated circulating creatine kinase-MB isoform (CK-MB) and myoglobin levels. Unexpectedly, greater elevations in circulating CK-MB and myoglobin above the control level were noted in the cooling trial during 48-72 hours of the post-exercise recovery period. Subjective fatigue feeling was greater at 72 hours after topical cooling compared with controls. Removal of the cold pack also led to a protracted rebound in muscle hemoglobin concentration compared with controls. Measures of interleukin (IL)-8, IL-10, IL-1ß, and muscle strength during recovery were not influenced by cooling. A peak shift in IL-12p70 was noted during recovery with topical cooling. These data suggest that topical cooling, a commonly used clinical intervention, seems to not improve but rather delay recovery from eccentric exercise-induced muscle damage.
Asunto(s)
Crioterapia/efectos adversos , Inflamación/terapia , Músculo Esquelético/lesiones , Recuperación de la Función , Entrenamiento de Fuerza , Biomarcadores/sangre , Forma MB de la Creatina-Quinasa , Estudios Cruzados , Citocinas/sangre , Articulación del Codo , Fatiga , Hemodinámica , Humanos , Inflamación/sangre , Estudios Longitudinales , Masculino , Fuerza Muscular , Músculo Esquelético/irrigación sanguínea , Mioglobina/sangre , Dolor , Adulto JovenRESUMEN
INTRODUCTION: Haemoglobinopathy testing is performed for carrier screening and evaluation of microcytic anaemia. We evaluated the effectiveness of thalassaemia screening tests at our institution and suggest ways of improving the testing algorithm. MATERIALS AND METHODS: A total of 10,084 non-antenatal and 11,364 antenatal samples with alkaline gel electrophoresis (AGE), capillary electrophoresis (CE), haemoglobin H (HbH) inclusion test, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were retrospectively reviewed. A subgroup of 187 samples with genetic testing was correlated with HbH inclusions and MCH/ MCV. The effect of iron deficiency on percentage hemoglobin A2 (HbA2) was studied. RESULTS: HbH inclusion test showed low sensitivity of 21.43% for α-thalassaemia mutations but higher sensitivity of 78.95% for --SEA deletion. By receiver operating characteristic (ROC) analysis, MCH ≤28 pg or MCV ≤80 fl for non-antenatal samples and MCH ≤27 pg or MCV ≤81 fl for antenatal samples had >98% sensitivity for HbH inclusions. Above these thresholds, the probability that HbH inclusions would be absent was <99% (negative predictive value [NPV] >99%). MCH ≥28 pg had 100% sensitivity (95% CI 95.63%-100%) for α-thalassaemia mutations and 97.68% calculated NPV in the antenatal population. Detection of haemoglobin variants by CE correlated highly with AGE (99.89% sensitivity, 100% specificity). Severe iron deficiency reduced HbA2 in hemoglobin (P <0.001) and α-thalassaemia (P = 0.0035), but not in ß-thalassaemia. CONCLUSION: MCH/MCV thresholds have adequate sensitivity for α-thalassaemia in the antenatal population, and genotyping plays an important role as HbH inclusion test shows low sensitivity. CE without AGE, may be used as initial screening for haemoglobin variants. Our study provides contemporary data to guide thalassaemia screening algorithms in Singapore.
Asunto(s)
Inclusiones Eritrocíticas/patología , Hemoglobina H/análisis , Complicaciones Hematológicas del Embarazo/diagnóstico , Talasemia alfa/diagnóstico , Electroforesis de las Proteínas Sanguíneas , Electroforesis Capilar , Índices de Eritrocitos , Femenino , Pruebas Genéticas , Humanos , Masculino , Tamizaje Masivo , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Estudios Retrospectivos , Sensibilidad y Especificidad , Singapur , Talasemia alfa/sangreRESUMEN
Circulating insulin concentration has been suggested as a biomarker for human longevity. The goal of the study was to determine the insulin levels under a glucose-challenged condition for the sedentary and physical active females in early middle age. We measured serum insulin levels for following groups: young sedentary (Y-SED, age 19.7 +/- 0.2 years), middle-aged sedentary (M-SED, age 42.3 +/- 3.1 years), young physically active (Y-EX, age 20.7 +/- 0.5 years), and middle-aged physically active (M-EX, age 40.3 +/- 2.8 years). Oral glucose tolerance test (OGTT) and insulin measurement were performed under overnight fasted condition. Triglyceride, cholesterol, body mass index (BMI), and waist-to-hip ratio (WHR) were also determined in all subjects. While fasted glucose and insulin levels were not different among 4 groups, glucose and insulin levels under OGTT were greater in the M-SED group than those in the Y-SED group. The M-EX subjects exhibited lower insulin levels on OGTT, as compared to the M-SED group, and were similar to the level of Y-SED. BMI and WHR of the M-SED group were comparable to those of the M-EX group. Triglyceride and cholesterol levels were highly associated with age and WHR but not the level of physical activity. The current study found a substantially greater insulin response on OGTT in the healthy sedentary females aged approximately 40, as compared to those in the young sedentary and the middle-aged physically active females, independent of weight status. The result of the study also suggests that accumulating 150 min of weekly exercise is sufficient to counteract the adverse effect of age on insulin sensitivity.
Asunto(s)
Ejercicio Físico/fisiología , Insulina/sangre , Adulto , Factores de Edad , Colesterol/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
BACKGROUND: The WHO defines three categories of NK cell malignancies; extra nodal NK/T cell lymphoma (NKTCL), aggressive NK cell leukemia, and the provisional entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC phenotype of NKTCL are limited. To the best of our knowledge ours is the first study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis (RNKL), and normal NK cells using eight color (8C) FC. METHODS: Specimens analyzed using the Euroflow8C NK Lymphoproliferative Disorder (NKLPD) panel between 2011 and 2014 were identified from our database. All samples were analyzed on the FACSCantoII cytometer. NK cells were identified as CD45+, smCD3-, CD19-, CD56+ and normal T-cells served as internal controls. RESULTS: The majority of NKTCL were CD56 bright, CD16 dim, CD57-, and CD94+. CLPD-NK and RNKL were predominantly CD56+ or dim with positive expression of CD16 and CD57 and weak CD94 expression. Antigen based statistical analyses showed robust division of samples along the NKTCL/normal CD56 bright NK cell and CLPD-NK/RNKL/normal CD56 positive NK cell groups. CONCLUSIONS: It was concluded that FC can reliably distinguish NKTCL from CLPD-NK, normal NK cells of CD56+ phenotype, and RNKL. It was proposed that the typical phenotype for NKTCL is: CD56 bright, CD16 dim with positive CD2, CD7, CD94, HLADR, CD25, CD26, and absent CD57. This resembles the phenotype of the CD56 bright immunoregulatory subset of NK cells which we therefore hypothesize is the cell of origin of NKTCL. © 2017 International Clinical Cytometry Society.
Asunto(s)
Proliferación Celular/fisiología , Células Asesinas Naturales/fisiología , Linfoma de Células T/fisiopatología , Antígenos CD/metabolismo , Citometría de Flujo/métodos , Humanos , Células Asesinas Naturales/metabolismo , Linfoma de Células T/metabolismo , Trastornos Linfoproliferativos/metabolismo , Trastornos Linfoproliferativos/fisiopatología , FenotipoRESUMEN
INTRODUCTION: Patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal or M-protein and skin changes) syndrome exhibit a wide range of clinical manifestations and are often seen by a variety of specialists prior to diagnosis. CLINICAL PICTURE: We describe a case of POEMS syndrome that first presented with significant neuropathy but progressed to develop further manifestations of the condition, including marked gastrointestinal symptoms. TREATMENT: The patient was commenced on localised radiotherapy and chemotherapy in addition to immunomodulatory therapy for the neuropathy. CONCLUSION: We highlight several learning points that may benefit physicians from varied specialties. This case is also unique for its marked gastrointestinal manifestation. To our knowledge, this is the second reported case in the literature with this feature.
Asunto(s)
Síndrome POEMS/tratamiento farmacológico , Síndrome POEMS/radioterapia , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Síndrome POEMS/complicaciones , Resultado del TratamientoRESUMEN
The purpose of the study was to compare glucose tolerance and insulin sensitivity between trained (TR) and competition (CP) states, in relation to cortisol and testosterone levels. Sixteen highly trained volleyball players voluntarily participated in this study. The first testing session (TR state) occurred 1 week before the start of national level volleyball CP, and the second testing session (CP state) occurred next morning after the 1-week CP. Fasted serum sample was used for measuring cortisol and testosterone. Subjects were then orally challenged with 75 g of glucose solution for determinations of oral glucose tolerance test (OGTT) and insulin response. Under both fasted and glucose challenged conditions, glucose levels of CP were not different from TR state, whereas insulin levels of CP were significantly elevated above TR (50 min: from 78.8 +/- 8.7 to 96.6 +/- 8.1 microU/ml, P < 0.05; 80 min: from 62.8 +/- 7.0 to 82.0 +/- 7.3; P < 0.05). Muscle creatine kinase (CK) level in blood was significantly increased above TR, suggesting greater muscle damage by CP. Serum leptin level, percent fat mass, and body weight were not different between two states. CP significantly increased serum cortisol level without significantly change in testosterone level. The new finding of the study was that volleyball CP reduced the whole-body insulin sensitivity significantly compared to TR state. The greater level of insulin concentration under CP state appears to be associated with elevated serum cortisol level. Despites the benefit of increased physical activity on metabolic function is widely recognized, physiological stress associated with CP can result in attenuation of systemic insulin sensitivity compared TR state.
Asunto(s)
Insulina/fisiología , Deportes/fisiología , Adolescente , Composición Corporal/fisiología , Creatina Quinasa/sangre , Prueba de Tolerancia a la Glucosa , Humanos , Hidrocortisona/sangre , Testosterona/sangreRESUMEN
Diagnosis of von Willebrand disease requires a combination of quantitative and qualitative tests including the von Willebrand factor ristocetin cofactor assay (vWF:RCo), the von Willebrand factor collagen binding assay (vWF:CB) and von Willebrand factor antigen quantification (vWF:Ag). Genetic factors, especially the ABO blood group, contribute significantly to the variation in vWF levels and function. Recent studies suggest that ethnicity may be another important modulator. We investigated the effect of the ABO blood group on these tests in 52 blood group O and 54 non-group O Chinese blood donors who were well-matched for sex and age distribution. Group O donors had significantly lower vWF:RCo, vWF:Ag and vWF:CB (P < 0.0001). Reduction in vWF:CB was greater than vWF:RCo in group O donors (53 versus 27%). This led to a lower vWF:CB/vWF:Ag ratio (P < 0.0001) in group O donors whereas the vWF:RCo/vWF:Ag ratio was unaffected (P = 0.97). These variations should be taken into consideration when interpreting these results in the Chinese.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/química , Colágeno/química , Pruebas Hematológicas , Ristocetina/química , Factor de von Willebrand/análisis , Pueblo Asiatico , Coagulación Sanguínea , Femenino , Pruebas Hematológicas/normas , Humanos , MasculinoRESUMEN
BACKGROUND: Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and are associated with enhanced patient sensitivity to warfarin. Interethnic differences in warfarin dose requirement have been described in the Asian population, and we postulate that this could be related to genetic variants of CYP2C9 that are unique to ethnic groups. METHODS: We prospectively genotyped 125 patients who were receiving a stable daily warfarin dose to maintain international normalized ratio values between 2 and 3 through comprehensive sequencing of the promoter and coding regions of the CYP2C9 gene. RESULTS: The mean weight-adjusted warfarin maintenance dose was significantly lower for Malay and Chinese subjects than Indian subjects ( P <.001 and.014, respectively). Warfarin dose negatively correlated with age (r = -0.4, P <.001) but not with sex. Multiple variants were detected in the promoter, exonic, intronic, and 3'-untranslated regions of CYP2C9, of which 16 were novel, including 7 nonsynonymous exonic variants ( 208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, and 1362G>C ). CYP2C9*3, but not CYP2C9*2, was found in Chinese and Malay patients, and carriers of the CYP2C9*3 variant in Chinese ( P <.01) and Indian ( P <.01) patients, but not Malay patients ( P =.77), required less warfarin. The influence of the novel exonic variants on warfarin dose requirement was unclear, because they were rare, but the lower warfarin dose requirement for Chinese and Malay patients existed despite omission of individuals with any coding region variants from analysis. CONCLUSIONS: Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies.
Asunto(s)
Anticoagulantes/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Warfarina/administración & dosificación , Adulto , Anciano , Alelos , Pueblo Asiatico , Citocromo P-450 CYP2C9 , Exones , Femenino , Ligamiento Genético , Genotipo , Humanos , Intrones , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Estudios ProspectivosRESUMEN
The RUNX1/AML1 gene is among the most frequently mutated genes in human leukaemia. However, its association with T-cell acute lymphoblastic leukaemia (T-ALL) remains poorly understood. In order to examine RUNX1 point mutations in T-ALL, we conducted an amplicon-based deep sequencing in 65 Southeast Asian childhood patients and 20 T-ALL cell lines, and detected RUNX1 mutations in 6 patients (9.2%) and 5 cell lines (25%). Interestingly, RUNX1-mutated T-ALL cases seem to constitute a subset of early immature T-ALL that may originate from differentiated T-cells. This result provides a deeper insight into the mechanistic basis for leukaemogenesis.
Asunto(s)
Diferenciación Celular/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Mutación Puntual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Adolescente , Línea Celular Tumoral , Niño , Preescolar , Femenino , Genes Codificadores de la Cadena gamma de los Receptores de Linfocito T , Humanos , Masculino , Eliminación de Secuencia , Adulto JovenAsunto(s)
Proteínas Potenciadoras de Unión a CCAAT/genética , Mutación de Línea Germinal , Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicos/diagnóstico , Adulto , Análisis Mutacional de ADN , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Síndromes Mielodisplásicos/genéticaRESUMEN
AIM: Hereditary thrombophilic markers are commonly screened among patients diagnosed as having venous thromboembolism, but optimal patient selection and the goals of screening may differ between populations. Determining the patterns of hereditary thrombophilia may improve screening strategies. METHOD: An unselected cohort of venous thromboembolism patients in three tertiary institutions in Singapore was prospectively tested for the prevalence of deficiencies of protein C, protein S, antithrombin III, factor V Leiden and prothrombin 20210 gene mutations. RESULTS: Among 384 patients screened, the prevalences of protein S, protein C and antithrombin III were 9.20%, 1.18% and 4.19% respectively. Only one patient was positive for the factor V Leiden mutation and none tested positive for the prothrombin 20210 gene mutation. At least 1 in 9 patients (11.52%, 95% CI 8.20 to 15.93) will test positive for one of the above markers in an unselected group of 269 patients who completed all tests. The exclusion of patients with clinical risk factors did not improve the detection rates, in comparison with those with obvious provoking clinical risk factors (11.72%, 95% CI 7.36 to 18.06 vs 11.29%, 95% CI 6.73 to 18.18). When upper age limits were set for thrombophilia screening by decades, a statistical difference in the likelihood of a positive thrombophilia screen between younger and older patient was seen for patients below 40 (p<0.001). CONCLUSION: In Singapore and countries with similar demographics, hereditary thrombophilia screening should be confined to testing for protein C, protein S and antithrombin III.
Asunto(s)
Deficiencia de Antitrombina III/genética , Predisposición Genética a la Enfermedad , Deficiencia de Proteína C/genética , Deficiencia de Proteína S/genética , Trombofilia/genética , Trombosis de la Vena/genética , Adulto , Anciano , Anciano de 80 o más Años , Deficiencia de Antitrombina III/complicaciones , Estudios de Cohortes , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Mutación , Deficiencia de Proteína C/complicaciones , Deficiencia de Proteína S/complicaciones , Singapur/epidemiología , Trombofilia/complicaciones , Trombofilia/epidemiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/epidemiología , Adulto JovenAsunto(s)
Mieloma Múltiple/patología , Derrame Pleural Maligno/patología , Anciano , Resultado Fatal , Femenino , HumanosRESUMEN
OBJECTIVE: The distribution of thiopurine methyltransferase (TPMT) activity in Asian populations has not been well documented. We studied the TPMT phenotype in three major Asian ethnic groups in Singapore, namely the Chinese (Ch), Malays (Mal) and Indians (Ind), with the aim of carrying out a comprehensive survey of the distribution of TPMT activity in Asians. METHODS: A radiochemical assay was used to measure the enzymatic activity of TPMT in the red blood cells (RBCs) of 479 healthy adults (Ch=153, Mal=163 and Ind=163). Cut-off points for intermediate TPMT activity were validated using a receiver operating curve (ROC) analysis. PCR-based methods were used to screen for the TPMT*3C, TPMT*3A and TPMT*6 variants. RESULTS: The histogram of the combined population cohort showed a bimodal distribution of TPMT activity, with no subject having low TPMT activity (<5 units). In total, TPMT variants were detected in 14 subjects (*1/*3C in 13 subjects; *1/*3A in one subject). We observed significant inter-ethnic differences in terms of TPMT activity (p<0.001), with the Malays showing a higher median activity than the Chinese or Indians (17.8 units vs 16.4 units). The Malays also showed a higher methylation rate--with a cut-off point for intermediate TPMT activity of 11.3 units--than the Chinese (9.9 units) or Indians (9.4 units). A high phenotype-genotype correlation of >97% was observed in all three races. We also genotyped 418 childhood leukaemias. The combined analysis of subjects participating in this and a previous study--1585 subjects--showed that 4.7% of Chinese (n=30/644), 4.4% of Malays (n=24/540) and 2.7% of Indians (n=11/401) were heterozygous at the TPMT gene locus. CONCLUSION: This is the first comprehensive TPMT phenotype and genotype study in Asian populations, particularly in the Malays and Indians.
Asunto(s)
Metiltransferasas/metabolismo , Adolescente , Adulto , Pueblo Asiatico , Niño , Preescolar , Estudios de Cohortes , Etnicidad , Femenino , Genotipo , Humanos , India/epidemiología , India/etnología , Lactante , Leucemia/enzimología , Leucemia/genética , Masculino , Persona de Mediana Edad , Fenotipo , Curva ROC , Reproducibilidad de los Resultados , Singapur/epidemiologíaRESUMEN
Athletes frequently adjust their training volume in line with their athletic competition schedule, onset of sport injury, and retirement. Whether maintenance of partial training activity during the detraining period can preserve optimal body composition and insulin sensitivity is currently unknown. Sixteen elite kayak athletes (mean VO2max: 58.5 ml.kg(-1).min(-1), s = 1.77) were randomly assigned to a totally detrained group (age: 20.8 years, s = 0.7; body mass index: 23.74, s = 0.54) or partially detrained group (age: 21.8 years, s = 0.7; body mass index: 23.20, s = 1.02), whereby totally detrained participants terminated their training routine completely and the partially detrained participants preserved approximately 50% of their previous training duration with equivalent intensity for one month. Body mass, waist circumference, oral glucose tolerance test, insulin, leptin, cortisol, and testosterone were measured during the trained state and after detraining. Waist circumferences for both the partially detrained and totally detrained groups were significantly elevated after detraining, with no group difference. However, body mass was reduced in both groups. Significant elevations in the area under the curve for insulin and fasted leptin with detraining were observed. These changes were greater in the totally detrained participants. In conclusion, the present results show that maintaining partial training activity cannot prevent an increase in waist circumference. During the detraining period, the magnitude of increase in plasma insulin and leptin concentrations was regulated in an activity-dependent manner.
Asunto(s)
Glucemia/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/sangre , Educación y Entrenamiento Físico/métodos , Deportes/fisiología , Adulto , Análisis de Varianza , Área Bajo la Curva , Índice de Masa Corporal , Prueba de Tolerancia a la Glucosa , Humanos , Leptina/sangre , Factores de TiempoRESUMEN
The development of nonmyeloablative (NM) hematopoietic cell transplantation (HCT) has extended the potential curative treatment option of allografting to patients in whom it was previously contraindicated because of advanced age or comorbidity. Acute and chronic graft versus host disease (GVHD) and its consequent nonrelapse mortality (NRM), remains the major limitation of NM HCT. In this report, we analyzed the outcome of 67 patients (median age, 45 years) with hematologic diseases receiving NM conditioning with fludarabine 90 mg/m(2) and total body irradiation (TBI) 200-cGy, followed by filgrastim-mobilized peripheral blood stem cell transplant from HLA identical (n = 61), 5/6 antigen-matched related (n = 1), 6/6 antigen-matched unrelated (n = 3), and 5/6 antigen-matched unrelated (n = 2) donors. The first cohort of 21 patients were given cyclosporine (CSP) and mycophenolate mofetil (MMF) as postgrafting immunosuppression, whereas the subsequent cohort was given additional methotrexate (MTX) and extended duration of CSP/MMF prophylaxis in an attempt to reduce graft-versus-host disease (GVHD). Sixty-four (95%) patients engrafted and 3 (5%) had secondary graft failure. Myelosuppression was moderate with neutrophil counts not declining below 500/microL in approximately 25% of patients, and with more than half of the patients not requiring any blood or platelet transfusion. The 2-year cumulative interval (CI) of grade II-IV, grade III-IV acute GVHD and chronic GVHD were 49%, 30%, and 34%, respectively. The 2-year probability of NRM, overall (OS), and progression-free (PFS) survival were 27%, 43%, and 28%, respectively. GVHD-related death accounted for 85% of NRM. Compared with patients receiving CSP/MMF, patients receiving extended duration of CSP/MMF with additional MTX in postgrafting immunosuppression had a significantly lower risk of grade III-IV acute GVHD (CI 20% versus 52%; P = .009) and NRM (CI at 2 years: 11% versus 62%; P < .001), without any significant adverse impact on the risk of relapse (CI at 2 years: 59% versus 33%; P = .174) Subgroup analysis of a cohort of patients given MTX/CSP/MMF showed that patients with "standard risk" diseases (n = 21) had a 3-year OS and PFS of 85% and 65%, respectively. This compares favorably to the 41% (P = .02) and 23% (P = .03) OS and PFS, respectively, in patients with "high-risk" diseases (n = 25). In conclusion, the addition of MTX onto the current postgrafting immunosuppression regimen with extended CSP/MMF prophylaxis duration provides more effective protection against severe GVHD, and is associated with more favorable outcome in patients receiving NM fludarabine/TBI conditioning than in patients receiving fludarabine/TBI conditioning with CSP and MMF without MTX.