RESUMEN
BACKGROUND AND OBJECTIVE: Hypophosphatasia is a rare inherited skeletal disorder characterized by defective bone mineralization and deficiency of tissue non-specific alkaline phosphatase (TNSALP) activity. The disease is caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding TNSALP. Early exfoliation of primary teeth owing to disturbed cementum formation, periodontal ligament weakness and alveolar bone resorption are major complications encountered in oral findings, and discovery of early loss of primary teeth in a dental examination often leads to early diagnosis of hypophosphatasia. Although there are no known fundamental treatments or effective dental approaches to prevent early exfoliation of primary teeth in affected patients, several possible treatments have recently been described, including gene therapy. Gene therapy has also been applied to TNSALP knockout mice (Alpl-/- ), which phenocopy the infantile form of hypophosphatasia, and improved their systemic condition. In the present study, we investigated whether gene therapy improved the dental condition of Alpl-/- mice. MATERIAL AND METHODS: Following sublethal irradiation (4 Gy) at the age of 2 d, Alpl-/- mice underwent gene therapy using bone marrow cells transduced with a lentiviral vector expressing a bone-targeted form of TNSALP injected into the jugular vein (n = 3). Wild-type (Alpl+/+ ), heterozygous mice (Alpl+/- ) and Alpl-/- mice were analyzed at 9 d of age (n = 3 of each), while Alpl+/+ mice and treated or untreated Alpl-/- mice were analyzed at 1 mo of age (n = 3 of each), and Alpl+/- mice and Alpl-/- mice with gene therapy were analyzed at 3 mo of age (n = 3 of each). A single mandibular hemi-section obtained at 1 mo of age was analyzed using a small animal computed tomography machine to assess alveolar bone formation. Other mandibular hemi-sections obtained at 9 d, 1 mo and 3 mo of age were subjected to hematoxylin and eosin staining and immunohistochemical analysis of osteopontin, a marker of cementum. RESULTS: Immunohistochemical analysis of osteopontin, a marker of acellular cementum, revealed that Alpl-/- mice displayed impaired formation of cementum and alveolar bone, similar to the human dental phenotype. Cementum formation was clearly present in Alpl-/- mice that underwent gene therapy, but did not recover to the same level as that in wild-type (Alpl+/+ ) mice. Micro-computed tomography examination showed that gene therapy improved alveolar bone mineral density in Alpl-/- mice to a similar level to that in Alpl+/+ mice. CONCLUSIONS: Our results suggest that gene therapy can improve the general condition of Alpl-/- mice, and induce significant alveolar bone formation and moderate improvement of cementum formation, which may contribute to inhibition of early spontaneous tooth exfoliation.
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Terapia Genética/métodos , Hipofosfatemia/terapia , Exfoliación Dental/etiología , Fosfatasa Alcalina/genética , Proceso Alveolar/patología , Animales , Densidad Ósea , Cemento Dental/patología , Modelos Animales de Enfermedad , Hipofosfatemia/complicaciones , Ratones , Ratones Noqueados , Exfoliación Dental/terapia , Resultado del TratamientoRESUMEN
Human gingival fibroblasts (hGFs) present an attractive source of induced pluripotent stem cells (iPSCs), which are expected to be a powerful tool for regenerative dentistry. However, problems to be addressed prior to clinical application include the use of animal-derived feeder cells for cultures. The aim of this study was to establish an autologous hGF-derived iPSC (hGF-iPSC) culture system by evaluating the feeder ability of hGFs. In both serum-containing and serum-free media, hGFs showed higher proliferation than human dermal fibroblasts (hDFs). Three hGF strains were isolated under serum-free conditions, although 2 showed impaired proliferation. When hGF-iPSCs were transferred onto mitomycin C-inactivated hGFs, hDFs, or mouse-derived SNL feeders, hGF and SNL feeders were clearly hGF-iPSC supportive for more than 50 passages, whereas hDF feeders were only able to maintain undifferentiated hGF-iPSC growth for a few passages. After 20 passages on hGF feeders, embryonic stem cell marker expression and CpG methylation at the NANOG and OCT3/4 promoters were similar for hGF-iPSCs cultured on hGF and SNL feeder cells. Long-term cultures of hGF-iPSCs on hGF feeders sustained their normal karyotype and pluripotency. On hGF feeders, hGF-iPSC colonies were surrounded by many colony-derived fibroblast-like cells, and the size of intact colonies at 7 d after passage was significantly larger than that on SNL feeders. Allogeneic hGF strains also maintained hGF-iPSCs for 10 passages. Compared with hDFs, hGFs showed a higher production of laminin-332, laminin α5 chain, and insulin-like growth factor-II, which have been reported to sustain the long-term self-renewal of pluripotent stem cells. These results suggest that hGFs possess an excellent feeder capability and thus can be used as alternatives to conventional mouse-derived SNL and hDF feeders. In addition, our findings suggest that hGF feeders are promising candidates for animal component-free ex vivo expansion of autologous hGF-iPSCs, thus providing an important step toward the future therapeutic application of hGF-iPSCs.
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Fibroblastos/fisiología , Encía/citología , Células Madre Pluripotentes Inducidas/fisiología , Adulto , Animales , Autoinjertos/citología , Moléculas de Adhesión Celular/análisis , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Movimiento Celular/fisiología , Proliferación Celular , Células Cultivadas , Islas de CpG/genética , Reactivos de Enlaces Cruzados/farmacología , Medios de Cultivo , Medio de Cultivo Libre de Suero , Fibroblastos/efectos de los fármacos , Proteínas de Homeodominio/análisis , Humanos , Factor II del Crecimiento Similar a la Insulina/análisis , Cariotipo , Laminina/análisis , Ratones , Persona de Mediana Edad , Mitomicina/farmacología , Proteína Homeótica Nanog , Factor 3 de Transcripción de Unión a Octámeros/análisis , Regiones Promotoras Genéticas/genética , Piel/citología , KalininaRESUMEN
STUDY DESIGN: Prospective analysis. OBJECTIVES: To investigate the influence of exercise and major competition on infectious episodes in athletes with spinal cord injuries (SCI). SETTING: Japan. METHODS: We examined the self-reported infectious episodes of upper respiratory tract infection (URTI) in athletes with SCI during a 1-month period before the race and 2 weeks after the race. The study included 21 persons with SCI who participated in the 18th Oita International Wheelchair Marathon. Thirteen persons with SCI who did not participate in the race were studied as control subjects. RESULTS: The number of URTI episodes in marathoners was 0.086+/-0.036/week during the 1-month period before the race and 0.089+/-0.040/week during the 2-week post-race period, whereas that of the controls was 0.139+/-0.046/week during the 1-month period before the race and 0.072+/-0.047/week during the 2-week post-race period. There were no significant differences between before and after the race in marathoners, or between marathoners and controls during each period. However, the number of URTI episodes 2 weeks after the race was significantly higher in subjects who trained more than 65 km/week compared to those who trained less than 65 km/week. CONCLUSIONS: In subjects with SCI who completed a wheelchair full marathon race, the incidence of URTI after the race was not high compared to control subjects who did not participate in the race. According to the number of URTI episodes and the training data, it is recommended that wheelchair marathoners should consider their risk for URTI during excessive practice.
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Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Carrera , Traumatismos de la Médula Espinal/fisiopatología , Deportes/fisiología , Silla de Ruedas , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid volume in the presence of fluid gain or loss. We hypothesized that IDVG has a close relationship with intrathoracic blood volume (ITBV), which has recently been used as an indicator of cardiac preload. We therefore examined whether IDVG can correlate with ITBV in various fluid volume states. METHODS: Fourteen anaesthetized mongrel dogs were mechanically ventilated. ITBV and cardiac output were measured by single transpulmonary thermodilution technique. IDVG and indocyanine green derived plasma volume (PV-ICG) were determined by the administration of 100 mg kg(-1) glucose and 0.5 mg kg(-1) indocyanine green solutions, respectively, and calculated by applying a one-compartment model. Three sets of measurements were performed before and after haemorrhage (30 mL kg(-1) and subsequent fluid volume loading (90 mL kg(-1) of lactated Ringer's solution). RESULTS: A linear correlation was observed between IDVG and ITBV (r2 = 0.52, n = 42, P < 0.001) and between PV-ICG and ITBV (r2 = 0.44, n = 42, P < 0.001) throughout the procedures. A linear correlation was also observed between changes in IDVG and those in ITBV (r2 = 0.76, n = 28, P < 0.001). The ITBV/IDVG ratio during normovolaemia was 0.26 +/- 0.04, which remained unchanged during the procedure. CONCLUSION: Results showed that that IDVG has a linear correlation with ITBV, and support the concept that IDVG measurement has potential as a surrogate measure of ITBV in various fluid volume states.
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Glucemia/análisis , Volumen Sanguíneo/fisiología , Glucosa/farmacocinética , Hipovolemia/fisiopatología , Animales , Gasto Cardíaco/fisiología , Colorantes , Perros , Líquido Extracelular/metabolismo , Hemorragia/fisiopatología , Hipotensión/fisiopatología , Hipovolemia/metabolismo , Verde de Indocianina , Soluciones Isotónicas/uso terapéutico , Sustitutos del Plasma/uso terapéutico , Volumen Plasmático/fisiología , Lactato de Ringer , Termodilución , TóraxRESUMEN
This report discusses the pathophysiology of and therapeutic methods to address hepatic vein anastomotic stricture after living donor liver transplantation (LDLT). From 1994 to 2002, our 15 LDLTs using the lateral segments or left lobes included four recipients who experienced 28 occurrences of this complication after the operation. The period between LDLT and the first stricture was 4.0 +/- 1.2 months. The age of the affected recipients (31.0 +/- 8.2 years) was significantly higher than that of the nonaffected patients (7.0 +/- 4.1 years, P < .05). Graft liver/standard liver volume ratio was 39.1% +/- 3.8% in the former and 77.9% +/- 12.7% in the latter cases (P < .05). Initial symptoms of stricture were ascites (42.9%), abdominal distention (42.9%), liver enzyme elevation (10.7%), and gastrointestinal bleeding (3.6%). In addition, 14 of 28 stricture cases (50%) showed increased blood trough levels of tacrolimus. Doppler ultrasonography was used for diagnosis, and balloon dilatations performed in all stricture patients, thereby hepatic significantly reducing venous blood pressure from 33.5 +/- 1.7 to 20.3 +/- 1.5 cmH2O. All patients finally resolved the strictures after several treatments. The stricture after LDLT was associated with small-for-size grafts, suggesting that liver regeneration may lead to anatomical changes and strictures. Since tacrolimus is metabolized by the liver, its blood trough level is one initial symptoms of stricture. Balloon dilatation was useful and safe as the treatment, while problems have been reported after stent insertion in the hepatic vein.
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Venas Hepáticas/patología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Enfermedades Vasculares/etiología , Adulto , Anastomosis Quirúrgica , Cateterismo/métodos , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Tiempo , Enfermedades Vasculares/terapiaRESUMEN
AIMS: The initial distribution volume of glucose (IDVG) has been proposed to provide a useful tool to estimate the central extracellular fluid volume. The purpose of this study was to determine the repetition interval of two consecutive measurements in haemodynamically stable patients without presence of recent changes in fluid status. METHODS: Twenty-nine patients admitted to the general intensive care unit of the University of Hirosaki Hospital were entered into this study. After achieving a haemodynamically stable state in each patient regardless of an infusion of vasoactive drugs, two glucose challenges at an interval of either 30 or 60 min, were carried out to calculate the IDVG. The IDVG was calculated using a one-compartment model after intravenous administration of glucose (5 g) followed by serial arterial blood sampling. RESULTS: Although plasma glucose levels immediately before the second glucose challenge in either group were increased compared with those of the first challenge (P < 0.001, respectively), the bias of the IDVG measurements was 0.08 +/- 0.32 L (SD) for the 30-min group and -0.19 +/- 0.28 L for the 60-min group. CONCLUSIONS: Our results indicate that IDVG determinations can be reliably repeated within a minimum interval of 30 min.
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Glucosa/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Glucemia , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Unidades de Cuidados Intensivos , Japón , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Distribución TisularRESUMEN
(1) Partial agonism is primarily dependent upon receptor density and coupling efficiency. As these parameters are tissue/model dependent, intrinsic activity in different tissues can vary. We have utilised the ecdysone-inducible expression system containing the human nociceptin/orphanin FQ (N/OFQ) peptide receptor (hNOP) expressed in Chinese hamster ovary cells (CHOINDhNOP) to examine the activity of a range of partial agonists in receptor binding, GTPgamma35S binding and inhibition of adenylyl cyclase studies. (2) Incubation of CHOINDhNOP cells with ponasterone A (PON) induced hNOP expression ([leucyl-3H]N/OFQ binding) of 24, 68, 191 and 1101 fmol mg-1 protein at 1, 2, 5 and 10 microm PON, respectively. At 191 fmol mg-1, protein hNOP pharmacology was identical to that reported for other traditional expression systems. (3) pEC50 values for GTPgamma35S binding ranged from 7.23 to 7.72 (2-10 microm PON) for the partial agonist [Phe1psi(CH2-NH)Gly2]N/OFQ(1-13)-NH2 ([F/G]N/OFQ(1-13)-NH2) and 8.12-8.60 (1-10 microm PON) for N/OFQ(1-13)-NH2 and Emax values (stimulation factor relative to basal) ranged from 1.51 to 3.21 (2-10 microm PON) for [F/G]N/OFQ(1-13)-NH2 and 1.28-6.95 (1-10 microm) for N/OFQ(1-13)-NH2. Intrinsic activity of [F/G]N/OFQ(1-13)-NH2 relative to N/OFQ(1-13)-NH2 was 0.3-0.5. [F/G]N/OFQ(1-13)-NH2 did not stimulate GTPgamma35S binding at 1 microm PON, but competitively antagonised the effects of N/OFQ(1-13)-NH2 with a pKB=7.62. (4) pEC50 values for cAMP inhibition ranged from 8.26 to 8.32 (2-10 microm PON) for [F/G]N/OFQ(1-13)-NH2 and 9.42-10.35 for N/OFQ(1-13)-NH2 and Emax values (% inhibition) ranged from 19.6 to 83.2 for [F/G]N/OFQ(1-13)-NH2 and 40.9-86.0 for N/OFQ(1-13)-NH2. The intrinsic activity of [F/G]N/OFQ(1-13)-NH2 relative to N/OFQ(1-13)-NH2 was 0.48-0.97. (5) In the same cellular environment with receptor density as the only variable, we show that the profile of [F/G]N/OFQ(1-13)-NH2 can be manipulated to encompass full and partial agonism along with antagonism.
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Regulación de la Expresión Génica/fisiología , Receptores Opioides/agonistas , Receptores Opioides/biosíntesis , Receptores de Esteroides/biosíntesis , Animales , Células CHO , Recuento de Células/métodos , Cricetinae , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Humanos , Unión Proteica/efectos de los fármacos , Unión Proteica/fisiología , Receptores de Esteroides/agonistas , Receptor de NociceptinaRESUMEN
OBJECTIVE: To investigate differences in triceps brachii endurance and electrical activity between elite marathon and recreational wheelchair athletes with paraplegia. DESIGN AND METHODS: Nine male elite wheelchair athletes between 20 and 46 years of age (average 29.0 +/- 8.2 years) with complete (ASIA-A) T4-L1 paraplegia were compared to a group of six male height- and weight-matched recreational wheelchair athletes with similar ages and injuries. Right triceps brachii maximum voluntary contraction (MVC), as well as the duration of the ability to maintain a 50% MVC were determined for all subjects. Median frequency (MF) and mean power frequency (MPF) were evaluated with fast Fourier transform spectrum analysis. MF and MPF rates of change were calculated and compared with the Student's t-test. SETTING: : Department of Rehabilitation Medicine, University of Occupational and Environmental Health, Japan. RESULTS: Right triceps brachii MVCs of the marathoners (42.4 +/- 8.8 N m (range 33-55 N m)) and recreational athletes (41.6 +/- 9.3 N m (range 32-56 N m)) did not differ significantly (P = 0.63). Endurance, however, did. All of the athletes, but none of the control subjects, were able to maintain a 50% MVC contraction of the right triceps brachii for 2 min (the average contraction duration in the latter group was 75.5+/-16.2 s). MF and MPF of the triceps brachii decreased linearly in both groups, but the slopes in the marathoners (-8.9 +/- 4.6 (-3.8 to -16.4) and -9.7 +/- 4.6 (-4.0 to -17.2)%/min, respectively) were statistically less steep than those in the recreational athletes (-22.3 +/- 8.2 (-9.6 to -31.4) and -21.2 +/- 6.4 (-11.4 to -28.6)%/min, respectively). CONCLUSION: Elite marathoners and active wheelchair users have similar triceps brachii strength. The marathoner's triceps brachii, however, display a significantly improved endurance and a slower decline of MF and MPF with time than do those of their recreational athlete control group.
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Contracción Muscular/fisiología , Fatiga Muscular/fisiología , Paraplejía/fisiopatología , Resistencia Física/fisiología , Carrera/fisiología , Silla de Ruedas , Adulto , Antropometría/métodos , Estudios de Casos y Controles , Codo/fisiología , Electromiografía/instrumentación , Electromiografía/métodos , Retroalimentación , Análisis de Fourier , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/etiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
BACKGROUND: Bone marrow (BM) cells have been shown to augment local angiogenesis by differentiating vessels themselves and/or secreting paracrinally angiogenic growth factors. Herein, the angiogenic effects of intra-arterial BM mononuclear cell (BM-MNC) transplantation were evaluated in a rat ischemic hindlimb model. METHODS: Unilateral hindlimb ischemia was created by excising the femoral artery and its branch in Lewis rats. BM-MNCs were isolated by centrifugation through a Histopaque density gradient. One week after excision of the unilateral femoral artery, BM-MNCs (5 x 10(6) cells, Group A, n = 6) or PBS (Group B, n = 7) were injected into the ischemic thigh skeletal muscles at the six points with a gauge needle. Another injection of BM-MNCs (3 x 10(7) cells, Group C, n = 6) or PBS (Group D, n = 7) was administered via the indwelling catheter in the right common iliac artery. RESULTS: Four weeks after the BM-MNC transplantation, angiographic examination revealed the development of collateral vessels in both BM-MNC-transplanted groups. The difference in skin temperature between right and left hindlimbs was significantly reduced in both BM-MNC-transplanted groups (0.93 +/- 0.15 vs. 2.84 +/- 0.35 vs. 1.20 +/- 0.26 vs. 2.61 +/- 0.37 degrees C, Group A vs. Group B vs. Group C vs. Group D, p < 0.05). Moreover, immunohistochemical analysis demonstrated that capillary endothelial cells were increased in both BM-MNC-transplanted groups. CONCLUSION: BM-MNC implantation was able to induce functional neovascularization in rat ischemic hindlimb. The intra-arterial administration offered similar levels of angiogenic activity as intramuscular injection.
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Trasplante de Médula Ósea , Isquemia/terapia , Neovascularización Fisiológica/fisiología , Angiografía , Animales , Miembro Posterior/irrigación sanguínea , Inmunohistoquímica , Infusiones Intraarteriales , Isquemia/fisiopatología , Masculino , Músculo Esquelético/química , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Ratas , Ratas Endogámicas Lew , Temperatura CutáneaRESUMEN
We have studied the effects of naloxone benzoylhydrazone (NalBzoH) at recombinant human OP4 receptors expressed in Chinese hamster ovary (CHO) cells (CHOhOP4) and native OP4 sites in isolated tissues from various species. In CHOhOP4 membranes, nociceptin (NC) and NalBzoH displaced [125I]Tyr14-NC with pKi values of 10.1 and 7.3. In the presence of 100 microM GDP, NC stimulated GTPgamma35S binding (pEC50 = 8.5). NalBzoH was ineffective but antagonized the effects of NC (pA2 = 6.9). At 5 microM GDP, there was an increase in potency (pEC50 = 9.3) and efficacy (4.3-fold) of NC. NalBzOH was a partial agonist (pEC50 = 7.0, Emax = 13% relative to NC). In CHOhOP4 cells, NC and NalBzoH inhibited cAMP formation with pEC50 and Emax values of 9.8 and 100% and 6.0 and 44%, respectively. In the rat vas deferens, NalBzoH (10 microM) did not modify electrically induced twitches but competitively antagonized the inhibitory action of NC (pA2 = 6.2). In the mouse vas deferens (mVD) and guinea pig ileum (gpI), NalBzoH inhibited twitches with pEC50 and Emax values of 7.6 and 78% and 8.5 and 77%, respectively. The effect of 3 microM NalBzoH was fully inhibited by 3 microM naloxone in mVD and 30 microM in gpI. Under these conditions, NalBzoH antagonized the actions of NC in both preparations with pA2 values of 6.3 and 6.8, respectively. Collectively, these data demonstrate that NalBzoH is a nonselective OP4 ligand with system-dependent behaviour.
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Naloxona/análogos & derivados , Naloxona/farmacología , Antagonistas de Narcóticos , Proteínas Recombinantes/antagonistas & inhibidores , Animales , Células CHO/efectos de los fármacos , Células CHO/metabolismo , Cricetinae , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Cobayas , Humanos , Técnicas In Vitro , Masculino , Ratones , Naloxona/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Opioides/agonistas , Receptores Opioides/metabolismo , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/metabolismo , Receptor de NociceptinaRESUMEN
Pulmonary alveolar proteinosis is often treated with bronchopulmonary lavage. Transoesophageal echocardiography has been used to detect lung atelectasis in critical situations. A 68-yr-old male with pulmonary alveolar proteinosis underwent bronchopulmonary lavage and was examined using transoesophageal echocardiography. His dependent left-lung area was observed through the descending aorta. Following saline infusion, no bright areas containing air were observed. The average area of the air-free region following instillation was 37.4 +/- 1.8 cm2, which decreased to 22.8 +/- 2.6 cm2 after drainage (P < 0.001). There was a significant relationship between the percentage venous admixture and air-free area during lavage (P < 0.05, r = -0.76). The image of the right lung was unclear. Transoesophageal echocardiography can yield useful information about the lung during bronchopulmonary lavage.
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Lavado Broncoalveolar , Ecocardiografía Transesofágica , Pulmón/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Anciano , Anestesia Intravenosa , Humanos , Masculino , Proteinosis Alveolar Pulmonar/complicaciones , Proteinosis Alveolar Pulmonar/terapia , Atelectasia Pulmonar/diagnóstico por imagen , Atelectasia Pulmonar/etiologíaRESUMEN
We investigated the potential use of rat amniotic epithelial (RAE) cells as donor cells for transplantation-based therapy in brain ischemia. In vitro, RAE cells were positive for both neuronal and neural stem cell markers, neurofilament microtubule-associated protein 2 and nestin. RT-PCR revealed that these cells express nestin mRNA. The RAE cells were transplanted into the hippocampus of adult gerbils that were subjected to temporal occlusion of bilateral carotid arteries. Five weeks after transplantation, grafted cells migrated into the CA1 pyramidal layer that showed selective neuronal death, and survived in a manner similar to CA1 pyramidal neurons. These results suggest that intracerebral transplantation of amniotic epithelial cells may have therapeutic potential for the treatment of ischemic damage in neuronal disorders.
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Amnios/citología , Isquemia Encefálica/terapia , Células Epiteliales/trasplante , Proteínas del Tejido Nervioso , Neuronas/citología , Animales , Movimiento Celular , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo/farmacología , Femenino , Expresión Génica , Gerbillinae , Hipocampo/citología , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/análisis , Proteínas de Filamentos Intermediarios/genética , Proteínas Asociadas a Microtúbulos/análisis , Nestina , Neuronas/química , Embarazo , ARN Mensajero/análisis , Ratas , Ratas WistarRESUMEN
This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.
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Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Proto-Oncogenes , Factores de Transcripción , Resultado del Tratamiento , Aclarubicina/administración & dosificación , Cromosomas Humanos Par 11 , Proteínas de Unión al ADN/genética , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Trasplante de Células Madre Hematopoyéticas , N-Metiltransferasa de Histona-Lisina , Humanos , Inmunofenotipificación , Lactante , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Mitoxantrona/administración & dosificación , Proteína de la Leucemia Mieloide-Linfoide , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Translocación Genética , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: We have reported that initial distribution volume of glucose indicates the central extracellular fluid volume in the presence of fluid gain or loss. The purpose of this study was to describe changes in initial distribution volume of glucose, plasma volume determined by the indocyanine green dilution method (PV-ICG), and thoracic fluid content by thoracic electrical bioimpedance in patients with or without apparent thoracic fluid accumulation in the absence of pleural effusion. We also sought to test whether initial distribution volume of glucose rather than PV-ICG mirrors thoracic fluid content. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Eleven consecutive patients with apparent thoracic fluid accumulation as judged by thoracic fluid content >0.05/ohm and underlying pathology and 20 consecutive acute myocardial infarction patients within 24 hrs after its onset were selected for study. None of the acute myocardial infarction patients had thoracic fluid content >0.05/ohm. INTERVENTIONS: Five grams of glucose and 25 mg of indocyanine green were administered simultaneously to calculate initial distribution volume of glucose and PV-ICG daily for the fluid-accumulated patients, and the same dosages were administered to the acute myocardial infarction patients immediately after their admission to the intensive care unit after percutaneous coronary angioplasty. Only the data on the day of the maximal and minimal thoracic fluid content in the fluid-accumulated patients were used for the study. The relationship between these two fluid volumes and thoracic fluid content was evaluated in the two patient groups. MEASUREMENTS AND MAIN RESULTS: Initial distribution volume of glucose and thoracic fluid content rather than PV-ICG and thoracic fluid content moved together in the same direction in each fluid-accumulated patient. Neither pulmonary artery occlusion pressure, central venous pressure, nor PV-ICG produced a better correlation with cardiac index when compared with initial distribution volume of glucose in patients with or without thoracic fluid accumulation. CONCLUSIONS: We suggest that initial distribution volume of glucose rather than PV-ICG is a better indicator of the intrathoracic blood volume status, even although intravenously administered glucose cannot stay in the intravascular compartment.
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Espacio Extracelular/metabolismo , Glucosa/farmacocinética , Infarto del Miocardio/metabolismo , Edema Pulmonar/metabolismo , Insuficiencia Respiratoria/metabolismo , APACHE , Adulto , Anciano , Glucemia , Impedancia Eléctrica , Femenino , Humanos , Verde de Indocianina/farmacocinética , Masculino , Persona de Mediana Edad , Volumen Plasmático , Respiración con Presión Positiva , Estudios Prospectivos , Distribución TisularRESUMEN
OBJECTIVE: To assess the effect of continuous hemodiafiltration (CHDF) on ketamine and midazolam kinetics in multiple organ dysfunction syndrome (MODS). DESIGN AND SETTING: Consecutive clinical study in a general intensive care unit of a university hospital. PATIENTS: Twelve adult patients with MODS requiring CHDF. MEASUREMENTS AND RESULTS: A total of 68 samples were collected during CHDF for ketamine, norketamine, and midazolam assays. The clearance values for ketamine and norketamine were 10.8 +/- 6.6 and 10.9 +/- 11.5 ml/min and their daily extractions were 21.4 +/- 7.1 and 10.2 +/- 11.5 mg/day, respectively. Midazolam was not eliminated through the filter during CHDF. There were no changes in Ramsay Sedation Score or Glasgow Coma Scale during CHDF. CONCLUSIONS: Small fractions of ketamine and norketamine were eliminated during CHDF in MODS. Midazolam was not eliminated during CHDF. CHDF did not affect the sedation using ketamine and midazolam even in MODS patients.
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Analgésicos/farmacocinética , Ansiolíticos/farmacocinética , Hemodiafiltración , Ketamina/farmacocinética , Midazolam/farmacocinética , Insuficiencia Multiorgánica/metabolismo , Analgésicos/sangre , Ansiolíticos/sangre , Femenino , Escala de Coma de Glasgow , Humanos , Ketamina/sangre , Masculino , Tasa de Depuración Metabólica , Midazolam/sangre , Persona de Mediana Edad , Insuficiencia Multiorgánica/terapiaRESUMEN
PURPOSE: To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS). RESULTS: The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. CONCLUSION: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.
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Antimetabolitos Antineoplásicos/administración & dosificación , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Punción Espinal , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Lactante , Inyecciones Espinales/efectos adversos , Japón/epidemiología , Tablas de Vida , Masculino , Recurrencia Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Prednisolona/administración & dosificación , Modelos de Riesgos Proporcionales , Riesgo , Sensibilidad y Especificidad , Punción Espinal/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The reaction of N,N'-dimethyl-N,N'-ethylenebis(5-bromo-3-formyl-2-hydroxybenzylaminato)copper(II) with ethylenediamine in aqueous DMF with excess perchloric acid resulted in the [2:2] cyclic condensation of the constituents, providing the dinuclear Cu(II) complex [Cu2(H2R)](ClO4)2. It crystallizes in the monoclinic space group P2(1)/c, with a = 19.603(3) A, b = 13.370(2) A, c = 21.072(3) A, beta = 98.87(1) degrees, V = 5456(1) A3, and Z = 4. The ligand R4- has two N(amine)2O2 and two N(imine)2O2 metal-binding sites sharing two phenolic oxygens, and [Cu2(H2R)](ClO4)2 has the two Cu(II) ions in the N(imine)2O2 sites and two protons in the N(amine)2O2 sites. [Cu2(H2R)](ClO4)2 was converted by neutralization into [Cu2(R)], from which mixed-metal Cu(II)2M(II)2 complexes [Cu2M2(R)Cl4] (M = Co(II), Ni(II), Zn(II)) were derived. [Cu2Co2(R)Cl4]*2CHCl3*H2O crystallizes in the monoclinic space group C2/c, with a = 32.514(3) A, b = 12.246(3) A, c = 19.827(2) A, beta = 126.082(1) degrees, V = 6380(1) A3, and Z = 4. [Cu2Zn2(R)Cl4]*2CHCl3*H2O crystallizes in the monoclinic space group C2/c, with a = 32.53(1) A, b = 12.242(2) A, c = 19.729(9) A, beta = 126.03(3) degrees, V = 6354(4) A3, and Z = 4. The two complexes are isotructural and have a dimer-of-dimers structure with two separated Cu(II)M(II) units. In each dinuclear unit, the Cu(II) is bound to the N(imine)2O2 site and the M(II) is bonded to a phenolic oxygen and two nitrogens of the N(amine)2O2 site. The Cu(II) and M(II) ions are bridged by a phenolic oxygen and an exogenous chloride ion. The Cu(II)2Ni(II)2 complex has a defect double-cubane structure. Cryomagnetic studies for the Cu(II)2Co(II)2 complex indicate an antiferromagnetic spin-exchange interaction within each dinuclear Cu(II)Co(II) unit (J = -9.5 cm(-1) based on H = -2JS(Cu)S(Co)). The Cu(II)2Ni(II)2 complex shows a weak antiferromagnetic interaction between the adjacent Cu(II) and Ni(II) ions (-3.5 cm(-1)) and a weak ferromagnetic interaction between the two Ni(II) ions (+2.0 cm(-1)).
RESUMEN
BACKGROUND: Densities in dependent lung regions worsen oxygenation in patients with acute respiratory distress syndrome. Identification of these densities requires examination using computed tomography (CT). In this study, the authors evaluated the use of transesophageal echocardiography (TEE) to estimate densities in the dependent lung. METHODS: Forty consecutive patients with acute lung injury or acute respiratory distress syndrome who underwent CT and TEE examination were included in this study. Densities in the lower left lung area were detected through the descending aorta by TEE. Density areas observed by TEE were compared with those obtained by CT. The effect of positive end-expiratory pressure (PEEP) application on density area was also evaluated. RESULTS: Density areas in the dependent lung region measured by TEE were 12.0+/-6.1 cm2 (mean +/- SD) at mid esophageal position. Density areas evaluated using TEE in the left lung correlated significantly with those estimated with CT in the left and right lungs (P < 0.01 in both lungs). In addition, the authors observed a significant correlation between PaO2/FIO2 and density areas estimated using TEE (P < 0.05). During positive end-expiratory pressure application, the area of density estimated with TEE decreased and PaO2 improved. CONCLUSIONS: The authors clearly demonstrated that it is possible to estimate the density area of the dependent left lung regions in patients with acute lung injury or acute respiratory distress syndrome using TEE. It is also possible to observe the changes of density areas during application of positive end-expiratory pressure.