RESUMEN
After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.
Asunto(s)
Mycobacterium tuberculosis/genética , Polimorfismo de Nucleótido Simple/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Brasil , Farmacorresistencia Bacteriana Múltiple/genética , Genotipo , Humanos , Filogenia , Grupos de PoblaciónRESUMEN
BACKGROUND: The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response could be modulated by supplementation with L-theanine. METHOD: The double-blind study included 20 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n = 10), receiving 150 mg of L-theanine extract for 6 weeks, or to the placebo group (n = 10). The participants performed a 2000-m test on a rowing ergometer at the beginning (1st examination) and at the end of the supplementation period (2nd examination). Blood samples were obtained from the antecubital vein before each exercise test, 1 min after completing the test, and after a 24-h recovery. Subpopulations of T regulatory lymphocytes (Tregs) (CD4+/CD25+/CD127-), cytotoxic lymphocytes (CTLs) (CD8+/TCRαß+), natural killer (NK) cells (CD3-/CD16+/CD56+) and TCRδγ-positive (Tδγ) cells were determined by means of flow cytometry. The levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 10 (IL-10), interferon gamma (INF-ɤ) and total antioxidant capacity (TAC) were determined with commercially available diagnostic kits. RESULTS: Supplementation with L-theanine contributed to a significant post-exercise decrease in IL-10 concentration, which was reflected by higher values of IL-2 to IL-10 and IFN-γ to IL-10 ratios. Moreover, a significant post-recovery decrease in CTL count, Treg to NK and Treg to CTL ratios was observed in the supplemented group. CONCLUSION: Despite the decrease in the number of some cytotoxic cells (CTLs) and an increase in the proportion of Tregs to CTLs, supplementation with LTE seems to exert a beneficial effect on a disrupted Th1/Th2 balance in elite athletes, as shown by the decrease in IL-10 concentration.
Asunto(s)
Suplementos Dietéticos , Ejercicio Físico , Glutamatos/administración & dosificación , Sistema Inmunológico/fisiología , Fenómenos Fisiológicos en la Nutrición Deportiva , Citocinas/sangre , Método Doble Ciego , Ergometría , Humanos , Células Asesinas Naturales/citología , Masculino , Linfocitos T Reguladores/citología , Deportes Acuáticos , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to analyse the effect of pomegranate juice (POM) supplementation on the levels of selected pro-inflammatory cytokines, hepcidin and markers of iron metabolism in well-trained rowers. METHOD: The double-blind placebo-controlled study included 19 members of the Polish Rowing Team. The athletes were randomised into the supplemented group (n = 10), receiving 50 ml of standardised POM daily for two months, or the placebo group (n = 9). The subjects performed a 2000 m test on the rowing ergometer at the start of the project (baseline) and end of follow-up period. Blood samples from the antecubital vein were obtained three times during each trial: prior to the exercise, one minute after the test, and following a 24 h recovery. RESULTS: The study documented the beneficial effect of supplementation with pomegranate fruit juice on TAC (P < 0.002). During the resting period, TAC level in the supplemented group was significantly higher than in the placebo group (x ± SD, 2.49 ± 0.39 vs. 1.88 ± 0.45, P < 0.05). The ergometric test conducted at baseline demonstrated a significant post-exercise increase in the concentrations of soluble transferrin receptors (P < 0.04), iron (P < 0.002) and IL-6 (P < 0.02), and to a significant post-exercise decrease in TAC. A significant increase in IL-6 concentration was also observed 24 h post-exercise. The exercise test conducted at the end of the follow-up period resulted in a significant decrease in TBIC and a significant increase in UIBC (P < 0.001), observed in both groups, both immediately post-exercise and after the resting period. CONCLUSION: Supplementation with POM contributed to a significant strengthening of plasma antioxidant potential in the group of well-trained rowers, but had no effect on iron metabolism markers.
Asunto(s)
Antioxidantes/metabolismo , Ejercicio Físico , Jugos de Frutas y Vegetales , Hierro/metabolismo , Lythraceae , Fenómenos Fisiológicos en la Nutrición Deportiva , Atletas , Biomarcadores/sangre , Método Doble Ciego , Ergometría , Humanos , Interleucina-6/sangre , Masculino , Adulto JovenRESUMEN
Study question: What is the diagnostic accuracy of 2D/3D hysterosalpingo-foam sonography (HyFoSy) and 2D/3D-high-definition flow Doppler (HDF)-HyFoSy in comparison to laparoscopy with dye chromotubation (as the reference method) and 2D air/saline-enhanced hysterosalpingo-contrast sonography (HyCoSy) (as the initial index test)? Summary answer: 2D/3D-HDF-HyFoSy had the best diagnostic accuracy and was the only method that did not significantly differ from the reference method, while both 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy had significantly higher accuracy than 2D-air/saline-HyCoSy. What is known already: Previous studies on X-ray hysterosalpingography and laparoscopy and dye as the reference standard have undermined the impact of older commercial contrast agents on the accuracy of ultrasound tubal patency tests. Recently, HyFoSy was reported to have very high accuracy in a small pilot study in comparison to laparoscopy and dye, and had a very high positive predictive value (PPV) for medical tubal occlusion. A new Doppler sonographic technique, known as HDF imaging with better axial resolution, fewer blooming artifacts and higher sensitivity than color and power Doppler imaging, has been introduced. Study design, size, duration: A prospective observational study was performed on 132 women (259 Fallopian tubes) consecutively enrolled between 2013 and 2015. Participants/materials, setting, methods: This study included infertile women of reproductive age who previously had not been examined for tubal patency and who presented for the evaluation to the university hospital, private hospital and clinic at which this study was conducted. 2D-Air/saline-HyCoSy, 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy and laparoscopy were performed independently by experienced readers. During HyFoSy, the 3D mode was used for standardization of pelvic scanning and observations of contrast flow without diagnosis after volume acquisition. Sensitivity, specificity, negative and positive predictive value (NPV and PPV), negative and positive-likelihood ratio (LR- and LR+) and 95% CI were calculated. McNemar's test and relative predictive values (a comparison of NPV and PPV) were used to compare all the index tests. Main results and the role of chance: 2D-Air/saline-HyCoSy, 2D/3D-HyFoSy and 2D/3D-HDF-HyFoSy indicated that 46 (17.8%), 27 (10.4%) and 24 (9.2%) of the 259 tubes were occluded, respectively; additionally, inconclusive results were obtained for 8 (3%), 5 (1.9%) and 3 (1.2%) tubes, respectively. The reference method revealed 18 (6.9%) occluded Fallopian tubes. 2D-Air/saline-HyCoSy had a high NPV (99.5%) that was similar to that of 2D/3D-HyFoSy (99%) and 2D/3D-HDF-HyFoSy (99.6%) (P > 0.05), but had a very low PPV (30.4%). The use of 2D/3D-HyFoSy, especially 2D/3D-HDF-HyFoSy, which had a significantly higher PPV (48% and 71%, P < 0.05 and P < 0.01; respectively), resulted in fewer false positive and inconclusive findings than the use of 2D-air/saline-HyCoSy. The LR- and LR+ was 0.14 and 14.8, respectively, for 2D/3D-HyFoSy, 0.06 and 32.1, respectively, for 2D/3D-HDF-HyFoSy, and 0.08 and 6.9, respectively, for 2D-air/saline-HyCoSy. The number of inconclusive or positive results per patient was significantly fewer with 2D/3D-HyFoSy (odds ratio, OR = 0.5, CI = 0.3-0.95, P < 0.05) and 2D/3D-HDF-HyFoSy (OR = 0.4, 95% CI = 0.2-0.8, P < 0.01) than with 2D-air/saline-HyCoSy. Limitations, reasons for caution: An unselected infertile population with a low prevalence of tubal occlusion is suitable for estimating the diagnostic accuracy of imaging tests only as a screening tool. Wider implications of the findings: These findings can be used to establish a diagnostic strategy with high accuracy but minimum invasiveness and limited use of contrast agents and sophisticated technology. 2D-Air/saline-HyCoSy, which has a high NPV, is suitable as an initial test and basic screening method, but 2D/3D-HDF-HyFoSy, which has a significantly higher PPV, can be used as a standard to verify any questionable or positive results obtained with 2D HyCoSy. This strategy may signficantly reduce the need for laparoscopy as a reference standard. Study funding/competing interest(s): There was no external funding for this study, and the authors have no conflicts of interest to declare. Trial registration number: N/A.
Asunto(s)
Trompas Uterinas/diagnóstico por imagen , Histerosalpingografía/métodos , Laparoscopía/métodos , Ultrasonografía/métodos , Adulto , Pruebas de Obstrucción de las Trompas Uterinas/métodos , Femenino , Humanos , Oportunidad Relativa , Sensibilidad y EspecificidadRESUMEN
The expansion of chemotherapy raised concerns about the health and safety of hospital personnel. Very little is known about the conditions of handling of chemotherapeutic agents by healthcare workers in Greece and possible adverse effects related to their safety practices, as well as the safety policies adopted by the Greek hospitals. A self-evaluation questionnaire was completed by 353 healthcare workers involved with the use of chemotherapeutic drugs in 24 Greek hospitals and the answers were statistically analysed. The majority of the healthcare workers are aware of the dangers of their work, although they had received limited training and medical surveillance. A significant percentage of them does not use personal protective equipment or use it inadequately. The safety design of their workplace is rather poor. Different health problems have been experienced, deriving from the respiratory, central nervous system, reproductive, gastrointestinal and musculoskeletal system. The improvement of safety training and procedures as well as medical surveillance seems to be a vital priority of hospital administration in Greece, in order to comply with the European guidelines and for the prevention of occupational diseases and environmental pollution.
Asunto(s)
Antineoplásicos/efectos adversos , Personal de Salud , Exposición Profesional , Administración de la Seguridad/normas , Adulto , Femenino , Grecia , Conocimientos, Actitudes y Práctica en Salud , Hospitales/normas , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Ropa de Protección/estadística & datos numéricos , Equipos de Seguridad/estadística & datos numéricos , Seguridad , Encuestas y CuestionariosRESUMEN
SETTING: Suruí Indians, Amazonia, Brazil. OBJECTIVE: To estimate the prevalence and the annual risk of infection (ARI) of tuberculosis (TB) in an indigenous population in Brazil. METHODS: We applied a method to estimate the prevalence of TB infection in populations with high bacille Calmette-Guérin (BCG) vaccine coverage. The method consisted of comparing levels of skin test reactivity in individuals tested with purified protein derivative (PPD) before and after stimulation with intradermal BCG. Fieldwork was carried out among the Suruí Indians (n = 993) in two phases, 3 months apart. RESULTS: A total of 645 subjects were tested. In pre-BCG revaccination, tuberculin skin test (TST) indurations averaged 5.9 mm (33.5% > or =10 mm). In post-BCG revaccination TST, indurations averaged 9.4 mm (48.7% > or =10 mm). Conversion from non-reactor to reactor was 54.4%. The ARI ranged from 1.2% to 2.2%. In the logistic regression, age and history of TB were the strongest independent predictors of TB infection. BCG scar and the number of individuals per house were also associated with infection. CONCLUSION: Tuberculous transmission is very high in the Suruí, surpassing the ARI reported for Brazil (0.6%). The epidemiology of TB in this indigenous population is related to unfavourable social and economic conditions, as well as to deficient health care services.
Asunto(s)
Indígenas Sudamericanos , Tuberculosis Pulmonar/etnología , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Vacuna BCG/uso terapéutico , Brasil/epidemiología , Brasil/etnología , Femenino , Humanos , Masculino , Grupos de Población , Prevalencia , Riesgo , Prueba de Tuberculina , Tuberculosis Pulmonar/prevención & control , VacunaciónRESUMEN
BACKGROUND: A nonhuman primate model of diabetes is valuable for assessing porcine pancreatic islet transplants that might have clinical benefits in humans. METHODS: Neonatal porcine islets, microencapsulated in alginate-polyornithine-alginate, were injected intraperitoneally (10,000 IEQs/kg islets) into eight adult male cynomolgus monkeys rendered diabetic with streptozotocin. Eight diabetic controls were given an equivalent dose of empty placebo capsules. All subjects received a repeat transplant 3 months after the first. RESULTS: The transplant was well tolerated and no adverse or hypoglycemic events occurred. There were two deaths from nontransplant treatment or diabetic complications unrelated to the transplants. After transplantation, the average insulin dose was reduced in the islet-treated group and increased in the control group. At 12 weeks after the first transplant there was a mean 36% (95% CI: 6% to 65%, P = .02) drop in daily insulin dose compared with the control group. After 24 weeks the difference increased to a mean of 43% (95% CI: 12% to 75%, P = .01) without significant differences in blood glucose values between the two groups. Individual responses after islet transplant varied and one monkey was weaned off insulin by 36 weeks. At terminal autopsy, organs appeared normal and there was no visible peritoneal reaction. No animal had polymerase chain reaction (PCR)-amplified signals of porcine endogenous retrovirus or exogenous virus infections in blood or tissues. CONCLUSION: Repeated intraperitoneal transplantation of microencapsulated neonatal porcine islets is a safe procedure in diabetic primates. It was shown to result in a significant reduction in insulin dose requirement in the majority of animals studied, whereas insulin requirement increased in controls.
Asunto(s)
Alginatos , Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/métodos , Trasplante Heterólogo/métodos , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Cápsulas , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Modelos Animales de Enfermedad , Ácido Glucurónico , Ácidos Hexurónicos , Insulina/uso terapéutico , Macaca fascicularis , Masculino , PorcinosRESUMEN
The aim of the study was to investigate the influence of an increased intake of anthocyanins, contained in chokeberry juice, on the redox parameters in rowers performing a physical exercise during a 1-month training camp. The athletes were randomly assigned to receive 150 mL of chokeberry juice daily, containing 23 mg/100 mL of anthocyanins (supplemented group), or placebo (control group). Before and after the supplementation period, the subjects performed an incremental rowing exercise test. Blood samples were taken from the antecubital vein before each exercise test, 1 min after the test, and following a 24-h recovery period. After the supplementation period, TBARS concentrations in the samples collected 1 min after the exercise test and following a 24-h recovery period were significantly lower in the subjects receiving chokeberry juice than in the control group. In the supplemented group, glutathione peroxidase activity was lower in the samples collected 1 min after the exercise test, and superoxide dismutase activity was lower in the samples taken following a 24-h recovery, as compared to the subjects receiving placebo. These findings indicate that an increased intake of anthocyanins limits the exercise-induced oxidative damage to red blood cells, most probably by enhancing the endogenous antioxidant defense system.
Asunto(s)
Antocianinas/administración & dosificación , Antioxidantes/administración & dosificación , Bebidas , Ejercicio Físico/fisiología , Estrés Oxidativo/efectos de los fármacos , Photinia/química , Adulto , Bebidas/análisis , Suplementos Dietéticos , Prueba de Esfuerzo , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Oxidación-Reducción , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Neural input plays a key role in the establishment of immune function, and environmental agents or drugs that interfere with the development of the nervous system elicit corresponding immunologic deficits. In the current study, we gave neonatal rats the widely used organophosphate pesticide, chlorpyrifos (CPF), and determined the immediate and long-term effects on T-lymphocyte function. Exposure of neonatal rats to 1 mg/kg of CPF daily on postnatal days (PN) 1-4 had no immediate effect (PN5) on T-cell mitogenic responses to concanavalin A challenge. However, once the animals reached adulthood, T-cell responses were significantly impaired. There were no deficits in basal T-cell replication rates, implying that the adverse effect of CPF exposure was specific to mitogenic activation. Treatment during a later neonatal period (PN11-14) elicited similar deficits in adulthood. CPF administration leads to inhibition of cholinesterase, and a cholinergic connection is supported by the fact that the results seen here correspond to those seen with a direct cholinergic stimulant (nicotine) administered during gestation or adolescence. These results indicate that exposure to CPF during a developmental period in which this organophosphate pesticide is known to produce lasting changes in neural function, elicits corresponding, long-term deficits in immune competence.
Asunto(s)
Cloropirifos/toxicidad , Inhibidores de la Colinesterasa/toxicidad , Sistema Inmunológico/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Neuroinmunomodulación/efectos de los fármacos , Factores de Edad , Animales , Animales Recién Nacidos , División Celular/efectos de los fármacos , División Celular/inmunología , Concanavalina A/farmacología , Femenino , Sistema Inmunológico/citología , Sistema Inmunológico/crecimiento & desarrollo , Mitógenos/farmacología , Sistema Nervioso/crecimiento & desarrollo , Sistema Nervioso/inmunología , Embarazo , Ratas , Ratas Sprague-Dawley , Linfocitos T/citología , Linfocitos T/efectos de los fármacosRESUMEN
Maternal cigarette smoking during pregnancy is known to alter immune function in the offspring and recent studies with animals indicate that prenatal nicotine exposure leads to lasting deficiencies in T-lymphocyte mitogenic responses, likely through excessive cholinergic stimulation during a critical stage of development. The current study was conducted to determine if the vulnerable period for nicotine-induced mis-programming of immune responses extends into adolescence, the stage at which most smokers begin tobacco use. Adolescent rats were given nicotine via osmotic minipump infusions on postnatal days (PN) 30-47.5, using a regimen that produces plasma levels (25 ng/ml) of nicotine similar to those in smokers or in users of transdermal nicotine patches. Toward the end of the infusion period (PN45) and 1 month after termination of nicotine exposure (PN80), we examined the mitogenic responses of splenocytes to Concanavalin A. Although no deficiencies were seen on PN45, there were robust decreases in mitogenic responses on PN80, with deficits apparent at both suboptimal and optimal concentrations of Concanavalin A. These results indicate that the adolescent immune system is vulnerable to nicotine-induced disruption of T-cell function.
Asunto(s)
Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/crecimiento & desarrollo , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Maduración Sexual/inmunología , Factores de Edad , Animales , Concanavalina A/farmacología , Femenino , Bombas de Infusión Implantables , Masculino , Mitógenos/farmacología , Ratas , Ratas Sprague-Dawley , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Endometrial cancer has become a more frequent neoplasm of the female genital tract. The role of lymphadenectomy in surgical treatment of this neoplasm has not been finally defined. The aim of the study was to determine relationship between pathological parameters of endometrial cancer and presence of metastases in pelvic lymph nodes. Forty one patients with endometrial cancer were treated by extended hysterectomy with pelvic lymphadenectomy. The precise Fisher test and logistic regression test were applied in the analysis of relationship. An intrinsic connection between presence of metastases in pelvic lymph nodes and cancer grade, depth of myometrium infiltration depth and infiltration of vascular spaces was found. On the other hand, histological type of neoplasm and characteristic of its growth does not seem to have connection with presence of metastases in pelvic lymph nodes. Pelvic lymphadenectomy seems to give profound information of of process advancement and indications for supplementary treatment.
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Carcinoma/patología , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Neoplasias Pélvicas/secundario , Adulto , Carcinoma/cirugía , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Metástasis Linfática/diagnósticoRESUMEN
Prenatal nicotine exposure has been shown to disrupt the development of a number of peripheral organs. In the current study, we examined the effects of gestational nicotine exposure, alone or in combination with ethanol exposure, on offspring immune function. Timed pregnant rats were treated with either nicotine (6 mg/kg/day) from gestation day 4-20 using subcutaneously implanted osmotic mini-pumps or ethanol administered in the drinking water (15% w/v) from gestation day 10-20. The combined exposure group received both treatments. The ability of offspring T and B cells to proliferate in response to nonspecific stimulation by Concanavalin A or lipopolysaccharide, respectively, was determined on postnatal days 9, 15, 22, 29, 64, and 86. Offspring splenocyte beta(2)-adrenoceptor binding was also measured. Nicotine or nicotine+ethanol suppressed splenocyte responsiveness to Concanavalin A or lipopolysaccharide which was similar in timing and magnitude to that seen with ethanol alone. Splenocytes from these groups remained subresponsive to stimulation well into adulthood. The combined drug treatment caused an overall reduction in spleen beta-adrenergic receptor binding whereas the individual drug treatments did not alter the development of spleen beta-adrenergic receptors.Our results indicate that prenatal nicotine exposure can cause long-term suppression of the proliferative response of offspring immune cells. Moreover, the effects of nicotine+ethanol may cause more severe deficits in adulthood.
Asunto(s)
Etanol/toxicidad , Feto/efectos de los fármacos , Tolerancia Inmunológica/efectos de los fármacos , Nicotina/toxicidad , Animales , Concanavalina A/farmacología , Femenino , Activación de Linfocitos/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta/análisis , Receptores Adrenérgicos beta/efectos de los fármacosRESUMEN
We report a case of gastric neurofibroma encountered in 41-year-old woman who complained of dyspepsia and physical examination revealed palpable mass in her abdomen. It was not possible to determine the nature and origin of the tumor by radiological and endoscopic investigations. At laparotomy the tumor was found to be pendiculated and growing extramurally from the anterior wall of the stomach. Wedge gastric resection, including the mass, was performed. Histological examination revealed a spindle cell gastric tumor, immunohistochemically differentiated as a neurofibroma.
Asunto(s)
Neurofibroma/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Dispepsia/etiología , Femenino , Humanos , Neurofibroma/complicaciones , Neurofibroma/cirugía , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugíaRESUMEN
PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/sangre , Distribución de Chi-Cuadrado , Ciclofosfamida/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Humanos , Interleucina-3/administración & dosificación , Interleucina-3/efectos adversos , Linfoma no Hodgkin/sangre , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Células Madre/efectos de los fármacos , Resultado del TratamientoRESUMEN
The Philadelphia (Ph) translocation t(9;22) results in the creation of the BCR-ABL gene, which is now regarded as central to the mechanism that underlies the chronic phase of chronic myelogenous leukemia (CML). From a clinical point of view, BCR-ABL mRNA detection has become the basis for the study of minimal residual disease in CML, particularly when a complete cytogenetic remission is achieved after interferon-alpha (IFN-alpha) therapy or allogeneic stem cell transplantation. We have recently demonstrated that it is possible to mobilize normal peripheral blood progenitor cells (PBPC) in higher rates if this procedure is performed during the early chronic phase. In an attempt to monitor the leukemic cell content of PBPC collections, we used quantitative-competitive RT-PCR (QC-RT-PCR). Thirty consecutive Philadelphia (Ph) chromosome positive patients were enrolled in this study. After chemotherapy and G-CSF, 14 patients achieved 100% Ph-negative metaphases, nine patients had < or =34% and seven patients >34% leukemic metaphases. A total of 116 collection samples were studied. For each sample, BCR-ABL transcript numbers and BCR-ABL/ABL ratio were evaluated. A highly significant correlation between Ph-positive metaphases and BCR-ABL transcript numbers (r = 0.84, P < 0.0001) or BCR-ABL/ABL ratio (r = 0.86, P < 0.0001) was found. For patients that underwent the procedure in early chronic phase, Ph-negative collections showed different levels of BCR-ABL expression. BCR-ABL transcript numbers varied from a median of 100/microg RNA in the first and second leukaphereses, to 500/microg RNA in the third and fourth leukaphereses, and 1500/microg RNA in the fifth leukapheresis (P = 0.002). BCR-ABL/ABL ratio values showed similar kinetics. We have also demonstrated that there is a correlation between low values in BCR-ABL/ABL ratio (< or =0.01) in the reinfused PBPC and the achievement of cytogenetic remission after autografting (chi2 test, P = 0.01). In conclusion, this study demonstrates that QC-RT-PCR for BCR-ABL is a reliable and helpful method for monitoring residual leukemic load in mobilized PBPC, particularly in Ph-negative collections. Moreover, QC-RT-PCR allows selection of the best available collections for reinfusion into patients after myeloablative therapy.
Asunto(s)
Proteínas de Fusión bcr-abl/genética , Células Madre Hematopoyéticas/citología , Leucaféresis , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/terapia , Adulto , Unión Competitiva , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Quimera por Trasplante , Trasplante AutólogoRESUMEN
Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility.
Asunto(s)
Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adulto , Femenino , Supervivencia de Injerto , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Trasplante AutólogoRESUMEN
The overall objective of this study was to analyze the effects of a combined prenatal and postnatal (entire gestational human chronic drinking model) ethanol exposure on T-cell development in mice. Specifically, this study evaluated the effects of chronic exposure to prenatal ethanol on lymphocyte makeup and proliferative capabilities of postnatal offspring's (4 and 12 weeks) peripheral lymphoid tissues. Chronic exposure regimens were conducted over the entire gestational period and through postnatal day 14 or 21. Thymus, spleen, and intestinal intraepithelial lymphocytes were harvested and analyzed by flow cytometry for percentages of T-cell subsets. Splenic lymphocytes were also analyzed for their ability to proliferate in response to a T-cell mitogen. Limited effects of chronic ethanol exposure were seen.
Asunto(s)
Subgrupos de Linfocitos B/inmunología , Trastornos del Espectro Alcohólico Fetal/inmunología , Subgrupos de Linfocitos T/inmunología , Animales , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Mucosa Intestinal/inmunología , Activación de Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Embarazo , Bazo/inmunología , Timo/inmunologíaRESUMEN
The optimal use of mitoxantrone (NOV) in the high-dose range requires elucidation of its maximum tolerated dose with peripheral blood progenitor cell (PBPC) support and the time interval needed between drug administration and PBPC reinfusion in order to avoid graft toxicity. The aims of this study were: (1) to verify the feasibility and haematological toxicity of escalating NOV up to 90 mg m(-2) with PBPC support; and (2) to verify the safeness of a short (96 h) interval between NOV administration and PBPC reinfusion. Three cohorts of ten patients with breast cancer (BC) or non-Hodgkin's lymphoma (NHL) received escalating doses of NOV, 60, 75 and 90 mg m(-2) plus melphalan (L-PAM), 140-180 mg m(-2), with PBPC rescue 96 h after NOV. Haematological toxicity was evaluated daily (WHO criteria). NOV plasma pharmacokinetics was also evaluated, as well as NOV cytotoxicity against PBPCs. Haematological recovery was rapid and complete at each NOV dose level without statistically significant differences, and there were no major toxicities. NOV plasma concentrations at the time of PBPC reinfusion were below the toxicity threshold against haemopoietic progenitors. It is concluded that, when adequately supported with PBPCs, NOV can be escalated up to 90 mg m(-2) with acceptable haematological toxicity. PBPCs can be safely reinfused as early as 96 h after NOV administration.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Células Madre Hematopoyéticas/efectos de los fármacos , Linfoma no Hodgkin/tratamiento farmacológico , Mitoxantrona/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Hematopoyesis/efectos de los fármacos , Humanos , Masculino , Melfalán/administración & dosificación , Mitoxantrona/farmacocinética , Mitoxantrona/toxicidadRESUMEN
The authors describe their experience about long-term VAD (Venous Access Devices) placement and in particular of placement techniques types of catheters, complications, and risk and benefit. 243 placements of VAD in 112 males and 131 females mainly affected by leukemia or breast cancer have been analyzed. 145 Leonard, 54 Groshong and 44 Hickman type silicon catheters have been implanted. The preferred access vein was the right internal jugular vein in 75% of patients and the right subclavian vein in the remained. The results show implant success in 98.7% of the patients. Complications have been rare and not serious and they have been divided into: 1) complications due to venipuncture, 2) complications during implant, 3) complications during the staying of catheter, 4) complications during the removal. The authors underline the advantages of puncture access through the right internal jugular vein in comparison with access through the right subclavian vein. Groshong type catheter is better than Leonard and Hickman. Very few infections have been noticed and patients seem to accept more willingly percutaneous placement than surgical one.
Asunto(s)
Cateterismo Venoso Central , Catéteres de Permanencia , Adolescente , Adulto , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. PATIENTS AND METHODS: The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. RESULTS: All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible. CONCLUSION: This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.